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Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland Department of Food and Nutritional Sciences University of Reading UK [email protected]
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Page 1: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Probiotics amp prebiotics in disease

- relevance for clinical practice

Ian Rowland

Department of Food and Nutritional Sciences

University of Reading UK

irowlandreadingacuk

What is a probiotic

Probiotics are live microorganisms which when administered in adequate amount confer a health benefit on the host (FAO 2001)

Usually comprise lactic acid producing bacteria (LAB) ndash Lactobacillus ndash Bifidobacterium

But others (Saccharomyces B coagulans

Closbutyricum E coli) also used

What do probiotics do

Types of evidence

bull In vitro experiments

bull Animal studies

bull Human studies ndash dietary interventions

ndash gt500 Randomized blinded placebo-controlled trials

bull Meta-analyses In several health areas there are

sufficient studies to combine them into a meta-analysis

ndash Provide more compelling evidence for efficacy

4

Potential benefits of probiotics

on human health

Weight management Growth of undernourished children

Oral microbiology bull Dental caries

Urogenital infections

Immune function Allergies

Skin microbiology

Gut function

Mental functionstress

Heart health

Good evidence- many human trials

Emerging evidence

Poor evidence ndash 1-2 trials

Key

Probiotics and immune function Many studies indicate that probiotics can modulate

immune status which has implications for

Upper respiratory tract infections (URTI)

Vaccination for influenza

Allergies eczema

Critically ill patients

Immunomodulation may also underlie effects of probiotics

on gut infections eg rotavirus diarrhoea

00

05

10

15

20

25

Placebo Probiotic

Sp

ecific

lysis

Before

After

L caseiShirotaamp

NK cell activity

Probiotics and respiratory

tract infections

Adults have an

average of 2ndash4

colds a year and

primary school

children have an

average of 3ndash8

In the USA 20 million

school days are lost per

annum

Probiotics reduce risk of URTI episodes

8

01 02 05 1 2

Favours probiotic Favours control

RR (95 CI)

Additional findings

Reduced use of antibiotics ( 33) Reduced risk of 3 or more URTI episodes ( 47)

study in children

^ study in marathon

runners

Overall RR = 058

( 42)

Identified 27 clinical trials 10 used for meta-analysis

Hao et al 2011 Cochrane Library 9

Probiotics and respiratory

infections

Berggren et al (2011) Eur J Nutr 50 203-210

Probiotic Lactplantarum HEAL9

Lactparacasei 87002

1 x 109 d

Target group Healthy adults (272) aged 18-65

Study design Double blind randomized placebo

controlled parallel study 12 weeks

Outcome markers Incidence duration and severity of

respiratory infections

Probiotics amp Colds

10

Control Probiotic

Duration of episode 86d 62d (Plt005)

Symptom score 444 336 (NS)

Berggren et al

EJN 2011

Probiotics and ADeczema

bull Prevalence of atopic dermatitis (AD) has risen over the

past decades especially in western societies Now 10-

20

bull 7 trials on prevention amp 12 trials on treatment

bull No consistent effects Van de Aa et al 2009 Boyle et al 2009

bull But some studies show certain strains are effective

11

Probiotics amp critically ill patients

Systematic review of 23 RPC trials in critically ill patients

bull Probiotics associated with reductions in

ndash Infectious complications RR 082 (95CI 069-089)

ndash Ventilator assoc pneumonia RR 075 (059-097)

ndash ICU mortality (trend) RR 080 (059-109)

bull No effect on length of stay in ICU or hospital

bull Clinical and statistical heterogeneity noted

Petrof et al Crit Care Med 40 3290 (2012)

NB Severe acute pancreatitis study showed probiotics associated with

increased mortality (bowel ischaemia) (Besselink et al Lancet 371 651-

9 2008)

12

13

Probiotics in elective surgery

bull Meta-analysis of 13 RPCTs (n=962) with preoperative

probiotics and synbiotics in patients undergoing elective

general surgical procedures

bull Incidence of postoperative sepsis was reduced

bull probiotic group OR= 042 95 CI 023-075 P = 003

bull synbiotic group OR = 025 95 CI 01-06 P = 002

bull No reduction in the incidence of pneumonia urinary tract

infections or wound infections in the postoperative phase

bull Synbiotics reduced the length of postoperative antibiotic

use (P = 003) Kinross et alJParenter Enteral Nutr 2013 37(2)243-53

Probiotics and gut health

Probiotics and gut health

bull Antibiotic associated diarrhoea (AAD)

bull Clostridium difficile (C diff)

bull Helicobacter pylori

bull Irritable bowel syndrome (IBS)

bull Acute infectious diarrhoea

bull Necrotizing enterocolitis (NEC)

bull Pouchitis

bull Travelers diarrhoea

bull Lactose maldigestion

bull Constipation

bull Colorectal cancer

bull Colic in infants

bull Inflammatory bowel conditions (UC CD)

15

Meta analysis

Probiotics reduce incidence

of many gut disorders ndash meta-analysis

16

RR (95 CI)

01 02 05 1 2 5

Favours probiotic Favours control

Ritchie ampRomanuk Plos1 7 2012

Overall RR = 058

( 42)

AAD

C difficile

H pylori

IBS

Infdiarrhoea

NEC

Pouchitis

Trav

diarrhoea

Total

043 (032-056)

059 (041-086)

066 (054-091)

077 (065-092)

035 (013-087)

039 (024-063)

017 (010-030)

092 (079-105)

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 2: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

What is a probiotic

Probiotics are live microorganisms which when administered in adequate amount confer a health benefit on the host (FAO 2001)

Usually comprise lactic acid producing bacteria (LAB) ndash Lactobacillus ndash Bifidobacterium

But others (Saccharomyces B coagulans

Closbutyricum E coli) also used

What do probiotics do

Types of evidence

bull In vitro experiments

bull Animal studies

bull Human studies ndash dietary interventions

ndash gt500 Randomized blinded placebo-controlled trials

bull Meta-analyses In several health areas there are

sufficient studies to combine them into a meta-analysis

ndash Provide more compelling evidence for efficacy

4

Potential benefits of probiotics

on human health

Weight management Growth of undernourished children

Oral microbiology bull Dental caries

Urogenital infections

Immune function Allergies

Skin microbiology

Gut function

Mental functionstress

Heart health

Good evidence- many human trials

Emerging evidence

Poor evidence ndash 1-2 trials

Key

Probiotics and immune function Many studies indicate that probiotics can modulate

immune status which has implications for

Upper respiratory tract infections (URTI)

Vaccination for influenza

Allergies eczema

Critically ill patients

Immunomodulation may also underlie effects of probiotics

on gut infections eg rotavirus diarrhoea

00

05

10

15

20

25

Placebo Probiotic

Sp

ecific

lysis

Before

After

L caseiShirotaamp

NK cell activity

Probiotics and respiratory

tract infections

Adults have an

average of 2ndash4

colds a year and

primary school

children have an

average of 3ndash8

In the USA 20 million

school days are lost per

annum

Probiotics reduce risk of URTI episodes

8

01 02 05 1 2

Favours probiotic Favours control

RR (95 CI)

Additional findings

Reduced use of antibiotics ( 33) Reduced risk of 3 or more URTI episodes ( 47)

study in children

^ study in marathon

runners

Overall RR = 058

( 42)

Identified 27 clinical trials 10 used for meta-analysis

Hao et al 2011 Cochrane Library 9

Probiotics and respiratory

infections

Berggren et al (2011) Eur J Nutr 50 203-210

Probiotic Lactplantarum HEAL9

Lactparacasei 87002

1 x 109 d

Target group Healthy adults (272) aged 18-65

Study design Double blind randomized placebo

controlled parallel study 12 weeks

Outcome markers Incidence duration and severity of

respiratory infections

Probiotics amp Colds

10

Control Probiotic

Duration of episode 86d 62d (Plt005)

Symptom score 444 336 (NS)

Berggren et al

EJN 2011

Probiotics and ADeczema

bull Prevalence of atopic dermatitis (AD) has risen over the

past decades especially in western societies Now 10-

20

bull 7 trials on prevention amp 12 trials on treatment

bull No consistent effects Van de Aa et al 2009 Boyle et al 2009

bull But some studies show certain strains are effective

11

Probiotics amp critically ill patients

Systematic review of 23 RPC trials in critically ill patients

bull Probiotics associated with reductions in

ndash Infectious complications RR 082 (95CI 069-089)

ndash Ventilator assoc pneumonia RR 075 (059-097)

ndash ICU mortality (trend) RR 080 (059-109)

bull No effect on length of stay in ICU or hospital

bull Clinical and statistical heterogeneity noted

Petrof et al Crit Care Med 40 3290 (2012)

NB Severe acute pancreatitis study showed probiotics associated with

increased mortality (bowel ischaemia) (Besselink et al Lancet 371 651-

9 2008)

12

13

Probiotics in elective surgery

bull Meta-analysis of 13 RPCTs (n=962) with preoperative

probiotics and synbiotics in patients undergoing elective

general surgical procedures

bull Incidence of postoperative sepsis was reduced

bull probiotic group OR= 042 95 CI 023-075 P = 003

bull synbiotic group OR = 025 95 CI 01-06 P = 002

bull No reduction in the incidence of pneumonia urinary tract

infections or wound infections in the postoperative phase

bull Synbiotics reduced the length of postoperative antibiotic

use (P = 003) Kinross et alJParenter Enteral Nutr 2013 37(2)243-53

Probiotics and gut health

Probiotics and gut health

bull Antibiotic associated diarrhoea (AAD)

bull Clostridium difficile (C diff)

bull Helicobacter pylori

bull Irritable bowel syndrome (IBS)

bull Acute infectious diarrhoea

bull Necrotizing enterocolitis (NEC)

bull Pouchitis

bull Travelers diarrhoea

bull Lactose maldigestion

bull Constipation

bull Colorectal cancer

bull Colic in infants

bull Inflammatory bowel conditions (UC CD)

15

Meta analysis

Probiotics reduce incidence

of many gut disorders ndash meta-analysis

16

RR (95 CI)

01 02 05 1 2 5

Favours probiotic Favours control

Ritchie ampRomanuk Plos1 7 2012

Overall RR = 058

( 42)

AAD

C difficile

H pylori

IBS

Infdiarrhoea

NEC

Pouchitis

Trav

diarrhoea

Total

043 (032-056)

059 (041-086)

066 (054-091)

077 (065-092)

035 (013-087)

039 (024-063)

017 (010-030)

092 (079-105)

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 3: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

What do probiotics do

Types of evidence

bull In vitro experiments

bull Animal studies

bull Human studies ndash dietary interventions

ndash gt500 Randomized blinded placebo-controlled trials

bull Meta-analyses In several health areas there are

sufficient studies to combine them into a meta-analysis

ndash Provide more compelling evidence for efficacy

4

Potential benefits of probiotics

on human health

Weight management Growth of undernourished children

Oral microbiology bull Dental caries

Urogenital infections

Immune function Allergies

Skin microbiology

Gut function

Mental functionstress

Heart health

Good evidence- many human trials

Emerging evidence

Poor evidence ndash 1-2 trials

Key

Probiotics and immune function Many studies indicate that probiotics can modulate

immune status which has implications for

Upper respiratory tract infections (URTI)

Vaccination for influenza

Allergies eczema

Critically ill patients

Immunomodulation may also underlie effects of probiotics

on gut infections eg rotavirus diarrhoea

00

05

10

15

20

25

Placebo Probiotic

Sp

ecific

lysis

Before

After

L caseiShirotaamp

NK cell activity

Probiotics and respiratory

tract infections

Adults have an

average of 2ndash4

colds a year and

primary school

children have an

average of 3ndash8

In the USA 20 million

school days are lost per

annum

Probiotics reduce risk of URTI episodes

8

01 02 05 1 2

Favours probiotic Favours control

RR (95 CI)

Additional findings

Reduced use of antibiotics ( 33) Reduced risk of 3 or more URTI episodes ( 47)

study in children

^ study in marathon

runners

Overall RR = 058

( 42)

Identified 27 clinical trials 10 used for meta-analysis

Hao et al 2011 Cochrane Library 9

Probiotics and respiratory

infections

Berggren et al (2011) Eur J Nutr 50 203-210

Probiotic Lactplantarum HEAL9

Lactparacasei 87002

1 x 109 d

Target group Healthy adults (272) aged 18-65

Study design Double blind randomized placebo

controlled parallel study 12 weeks

Outcome markers Incidence duration and severity of

respiratory infections

Probiotics amp Colds

10

Control Probiotic

Duration of episode 86d 62d (Plt005)

Symptom score 444 336 (NS)

Berggren et al

EJN 2011

Probiotics and ADeczema

bull Prevalence of atopic dermatitis (AD) has risen over the

past decades especially in western societies Now 10-

20

bull 7 trials on prevention amp 12 trials on treatment

bull No consistent effects Van de Aa et al 2009 Boyle et al 2009

bull But some studies show certain strains are effective

11

Probiotics amp critically ill patients

Systematic review of 23 RPC trials in critically ill patients

bull Probiotics associated with reductions in

ndash Infectious complications RR 082 (95CI 069-089)

ndash Ventilator assoc pneumonia RR 075 (059-097)

ndash ICU mortality (trend) RR 080 (059-109)

bull No effect on length of stay in ICU or hospital

bull Clinical and statistical heterogeneity noted

Petrof et al Crit Care Med 40 3290 (2012)

NB Severe acute pancreatitis study showed probiotics associated with

increased mortality (bowel ischaemia) (Besselink et al Lancet 371 651-

9 2008)

12

13

Probiotics in elective surgery

bull Meta-analysis of 13 RPCTs (n=962) with preoperative

probiotics and synbiotics in patients undergoing elective

general surgical procedures

bull Incidence of postoperative sepsis was reduced

bull probiotic group OR= 042 95 CI 023-075 P = 003

bull synbiotic group OR = 025 95 CI 01-06 P = 002

bull No reduction in the incidence of pneumonia urinary tract

infections or wound infections in the postoperative phase

bull Synbiotics reduced the length of postoperative antibiotic

use (P = 003) Kinross et alJParenter Enteral Nutr 2013 37(2)243-53

Probiotics and gut health

Probiotics and gut health

bull Antibiotic associated diarrhoea (AAD)

bull Clostridium difficile (C diff)

bull Helicobacter pylori

bull Irritable bowel syndrome (IBS)

bull Acute infectious diarrhoea

bull Necrotizing enterocolitis (NEC)

bull Pouchitis

bull Travelers diarrhoea

bull Lactose maldigestion

bull Constipation

bull Colorectal cancer

bull Colic in infants

bull Inflammatory bowel conditions (UC CD)

15

Meta analysis

Probiotics reduce incidence

of many gut disorders ndash meta-analysis

16

RR (95 CI)

01 02 05 1 2 5

Favours probiotic Favours control

Ritchie ampRomanuk Plos1 7 2012

Overall RR = 058

( 42)

AAD

C difficile

H pylori

IBS

Infdiarrhoea

NEC

Pouchitis

Trav

diarrhoea

Total

043 (032-056)

059 (041-086)

066 (054-091)

077 (065-092)

035 (013-087)

039 (024-063)

017 (010-030)

092 (079-105)

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 4: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Types of evidence

bull In vitro experiments

bull Animal studies

bull Human studies ndash dietary interventions

ndash gt500 Randomized blinded placebo-controlled trials

bull Meta-analyses In several health areas there are

sufficient studies to combine them into a meta-analysis

ndash Provide more compelling evidence for efficacy

4

Potential benefits of probiotics

on human health

Weight management Growth of undernourished children

Oral microbiology bull Dental caries

Urogenital infections

Immune function Allergies

Skin microbiology

Gut function

Mental functionstress

Heart health

Good evidence- many human trials

Emerging evidence

Poor evidence ndash 1-2 trials

Key

Probiotics and immune function Many studies indicate that probiotics can modulate

immune status which has implications for

Upper respiratory tract infections (URTI)

Vaccination for influenza

Allergies eczema

Critically ill patients

Immunomodulation may also underlie effects of probiotics

on gut infections eg rotavirus diarrhoea

00

05

10

15

20

25

Placebo Probiotic

Sp

ecific

lysis

Before

After

L caseiShirotaamp

NK cell activity

Probiotics and respiratory

tract infections

Adults have an

average of 2ndash4

colds a year and

primary school

children have an

average of 3ndash8

In the USA 20 million

school days are lost per

annum

Probiotics reduce risk of URTI episodes

8

01 02 05 1 2

Favours probiotic Favours control

RR (95 CI)

Additional findings

Reduced use of antibiotics ( 33) Reduced risk of 3 or more URTI episodes ( 47)

study in children

^ study in marathon

runners

Overall RR = 058

( 42)

Identified 27 clinical trials 10 used for meta-analysis

Hao et al 2011 Cochrane Library 9

Probiotics and respiratory

infections

Berggren et al (2011) Eur J Nutr 50 203-210

Probiotic Lactplantarum HEAL9

Lactparacasei 87002

1 x 109 d

Target group Healthy adults (272) aged 18-65

Study design Double blind randomized placebo

controlled parallel study 12 weeks

Outcome markers Incidence duration and severity of

respiratory infections

Probiotics amp Colds

10

Control Probiotic

Duration of episode 86d 62d (Plt005)

Symptom score 444 336 (NS)

Berggren et al

EJN 2011

Probiotics and ADeczema

bull Prevalence of atopic dermatitis (AD) has risen over the

past decades especially in western societies Now 10-

20

bull 7 trials on prevention amp 12 trials on treatment

bull No consistent effects Van de Aa et al 2009 Boyle et al 2009

bull But some studies show certain strains are effective

11

Probiotics amp critically ill patients

Systematic review of 23 RPC trials in critically ill patients

bull Probiotics associated with reductions in

ndash Infectious complications RR 082 (95CI 069-089)

ndash Ventilator assoc pneumonia RR 075 (059-097)

ndash ICU mortality (trend) RR 080 (059-109)

bull No effect on length of stay in ICU or hospital

bull Clinical and statistical heterogeneity noted

Petrof et al Crit Care Med 40 3290 (2012)

NB Severe acute pancreatitis study showed probiotics associated with

increased mortality (bowel ischaemia) (Besselink et al Lancet 371 651-

9 2008)

12

13

Probiotics in elective surgery

bull Meta-analysis of 13 RPCTs (n=962) with preoperative

probiotics and synbiotics in patients undergoing elective

general surgical procedures

bull Incidence of postoperative sepsis was reduced

bull probiotic group OR= 042 95 CI 023-075 P = 003

bull synbiotic group OR = 025 95 CI 01-06 P = 002

bull No reduction in the incidence of pneumonia urinary tract

infections or wound infections in the postoperative phase

bull Synbiotics reduced the length of postoperative antibiotic

use (P = 003) Kinross et alJParenter Enteral Nutr 2013 37(2)243-53

Probiotics and gut health

Probiotics and gut health

bull Antibiotic associated diarrhoea (AAD)

bull Clostridium difficile (C diff)

bull Helicobacter pylori

bull Irritable bowel syndrome (IBS)

bull Acute infectious diarrhoea

bull Necrotizing enterocolitis (NEC)

bull Pouchitis

bull Travelers diarrhoea

bull Lactose maldigestion

bull Constipation

bull Colorectal cancer

bull Colic in infants

bull Inflammatory bowel conditions (UC CD)

15

Meta analysis

Probiotics reduce incidence

of many gut disorders ndash meta-analysis

16

RR (95 CI)

01 02 05 1 2 5

Favours probiotic Favours control

Ritchie ampRomanuk Plos1 7 2012

Overall RR = 058

( 42)

AAD

C difficile

H pylori

IBS

Infdiarrhoea

NEC

Pouchitis

Trav

diarrhoea

Total

043 (032-056)

059 (041-086)

066 (054-091)

077 (065-092)

035 (013-087)

039 (024-063)

017 (010-030)

092 (079-105)

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 5: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Potential benefits of probiotics

on human health

Weight management Growth of undernourished children

Oral microbiology bull Dental caries

Urogenital infections

Immune function Allergies

Skin microbiology

Gut function

Mental functionstress

Heart health

Good evidence- many human trials

Emerging evidence

Poor evidence ndash 1-2 trials

Key

Probiotics and immune function Many studies indicate that probiotics can modulate

immune status which has implications for

Upper respiratory tract infections (URTI)

Vaccination for influenza

Allergies eczema

Critically ill patients

Immunomodulation may also underlie effects of probiotics

on gut infections eg rotavirus diarrhoea

00

05

10

15

20

25

Placebo Probiotic

Sp

ecific

lysis

Before

After

L caseiShirotaamp

NK cell activity

Probiotics and respiratory

tract infections

Adults have an

average of 2ndash4

colds a year and

primary school

children have an

average of 3ndash8

In the USA 20 million

school days are lost per

annum

Probiotics reduce risk of URTI episodes

8

01 02 05 1 2

Favours probiotic Favours control

RR (95 CI)

Additional findings

Reduced use of antibiotics ( 33) Reduced risk of 3 or more URTI episodes ( 47)

study in children

^ study in marathon

runners

Overall RR = 058

( 42)

Identified 27 clinical trials 10 used for meta-analysis

Hao et al 2011 Cochrane Library 9

Probiotics and respiratory

infections

Berggren et al (2011) Eur J Nutr 50 203-210

Probiotic Lactplantarum HEAL9

Lactparacasei 87002

1 x 109 d

Target group Healthy adults (272) aged 18-65

Study design Double blind randomized placebo

controlled parallel study 12 weeks

Outcome markers Incidence duration and severity of

respiratory infections

Probiotics amp Colds

10

Control Probiotic

Duration of episode 86d 62d (Plt005)

Symptom score 444 336 (NS)

Berggren et al

EJN 2011

Probiotics and ADeczema

bull Prevalence of atopic dermatitis (AD) has risen over the

past decades especially in western societies Now 10-

20

bull 7 trials on prevention amp 12 trials on treatment

bull No consistent effects Van de Aa et al 2009 Boyle et al 2009

bull But some studies show certain strains are effective

11

Probiotics amp critically ill patients

Systematic review of 23 RPC trials in critically ill patients

bull Probiotics associated with reductions in

ndash Infectious complications RR 082 (95CI 069-089)

ndash Ventilator assoc pneumonia RR 075 (059-097)

ndash ICU mortality (trend) RR 080 (059-109)

bull No effect on length of stay in ICU or hospital

bull Clinical and statistical heterogeneity noted

Petrof et al Crit Care Med 40 3290 (2012)

NB Severe acute pancreatitis study showed probiotics associated with

increased mortality (bowel ischaemia) (Besselink et al Lancet 371 651-

9 2008)

12

13

Probiotics in elective surgery

bull Meta-analysis of 13 RPCTs (n=962) with preoperative

probiotics and synbiotics in patients undergoing elective

general surgical procedures

bull Incidence of postoperative sepsis was reduced

bull probiotic group OR= 042 95 CI 023-075 P = 003

bull synbiotic group OR = 025 95 CI 01-06 P = 002

bull No reduction in the incidence of pneumonia urinary tract

infections or wound infections in the postoperative phase

bull Synbiotics reduced the length of postoperative antibiotic

use (P = 003) Kinross et alJParenter Enteral Nutr 2013 37(2)243-53

Probiotics and gut health

Probiotics and gut health

bull Antibiotic associated diarrhoea (AAD)

bull Clostridium difficile (C diff)

bull Helicobacter pylori

bull Irritable bowel syndrome (IBS)

bull Acute infectious diarrhoea

bull Necrotizing enterocolitis (NEC)

bull Pouchitis

bull Travelers diarrhoea

bull Lactose maldigestion

bull Constipation

bull Colorectal cancer

bull Colic in infants

bull Inflammatory bowel conditions (UC CD)

15

Meta analysis

Probiotics reduce incidence

of many gut disorders ndash meta-analysis

16

RR (95 CI)

01 02 05 1 2 5

Favours probiotic Favours control

Ritchie ampRomanuk Plos1 7 2012

Overall RR = 058

( 42)

AAD

C difficile

H pylori

IBS

Infdiarrhoea

NEC

Pouchitis

Trav

diarrhoea

Total

043 (032-056)

059 (041-086)

066 (054-091)

077 (065-092)

035 (013-087)

039 (024-063)

017 (010-030)

092 (079-105)

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 6: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Probiotics and immune function Many studies indicate that probiotics can modulate

immune status which has implications for

Upper respiratory tract infections (URTI)

Vaccination for influenza

Allergies eczema

Critically ill patients

Immunomodulation may also underlie effects of probiotics

on gut infections eg rotavirus diarrhoea

00

05

10

15

20

25

Placebo Probiotic

Sp

ecific

lysis

Before

After

L caseiShirotaamp

NK cell activity

Probiotics and respiratory

tract infections

Adults have an

average of 2ndash4

colds a year and

primary school

children have an

average of 3ndash8

In the USA 20 million

school days are lost per

annum

Probiotics reduce risk of URTI episodes

8

01 02 05 1 2

Favours probiotic Favours control

RR (95 CI)

Additional findings

Reduced use of antibiotics ( 33) Reduced risk of 3 or more URTI episodes ( 47)

study in children

^ study in marathon

runners

Overall RR = 058

( 42)

Identified 27 clinical trials 10 used for meta-analysis

Hao et al 2011 Cochrane Library 9

Probiotics and respiratory

infections

Berggren et al (2011) Eur J Nutr 50 203-210

Probiotic Lactplantarum HEAL9

Lactparacasei 87002

1 x 109 d

Target group Healthy adults (272) aged 18-65

Study design Double blind randomized placebo

controlled parallel study 12 weeks

Outcome markers Incidence duration and severity of

respiratory infections

Probiotics amp Colds

10

Control Probiotic

Duration of episode 86d 62d (Plt005)

Symptom score 444 336 (NS)

Berggren et al

EJN 2011

Probiotics and ADeczema

bull Prevalence of atopic dermatitis (AD) has risen over the

past decades especially in western societies Now 10-

20

bull 7 trials on prevention amp 12 trials on treatment

bull No consistent effects Van de Aa et al 2009 Boyle et al 2009

bull But some studies show certain strains are effective

11

Probiotics amp critically ill patients

Systematic review of 23 RPC trials in critically ill patients

bull Probiotics associated with reductions in

ndash Infectious complications RR 082 (95CI 069-089)

ndash Ventilator assoc pneumonia RR 075 (059-097)

ndash ICU mortality (trend) RR 080 (059-109)

bull No effect on length of stay in ICU or hospital

bull Clinical and statistical heterogeneity noted

Petrof et al Crit Care Med 40 3290 (2012)

NB Severe acute pancreatitis study showed probiotics associated with

increased mortality (bowel ischaemia) (Besselink et al Lancet 371 651-

9 2008)

12

13

Probiotics in elective surgery

bull Meta-analysis of 13 RPCTs (n=962) with preoperative

probiotics and synbiotics in patients undergoing elective

general surgical procedures

bull Incidence of postoperative sepsis was reduced

bull probiotic group OR= 042 95 CI 023-075 P = 003

bull synbiotic group OR = 025 95 CI 01-06 P = 002

bull No reduction in the incidence of pneumonia urinary tract

infections or wound infections in the postoperative phase

bull Synbiotics reduced the length of postoperative antibiotic

use (P = 003) Kinross et alJParenter Enteral Nutr 2013 37(2)243-53

Probiotics and gut health

Probiotics and gut health

bull Antibiotic associated diarrhoea (AAD)

bull Clostridium difficile (C diff)

bull Helicobacter pylori

bull Irritable bowel syndrome (IBS)

bull Acute infectious diarrhoea

bull Necrotizing enterocolitis (NEC)

bull Pouchitis

bull Travelers diarrhoea

bull Lactose maldigestion

bull Constipation

bull Colorectal cancer

bull Colic in infants

bull Inflammatory bowel conditions (UC CD)

15

Meta analysis

Probiotics reduce incidence

of many gut disorders ndash meta-analysis

16

RR (95 CI)

01 02 05 1 2 5

Favours probiotic Favours control

Ritchie ampRomanuk Plos1 7 2012

Overall RR = 058

( 42)

AAD

C difficile

H pylori

IBS

Infdiarrhoea

NEC

Pouchitis

Trav

diarrhoea

Total

043 (032-056)

059 (041-086)

066 (054-091)

077 (065-092)

035 (013-087)

039 (024-063)

017 (010-030)

092 (079-105)

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 7: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Probiotics and respiratory

tract infections

Adults have an

average of 2ndash4

colds a year and

primary school

children have an

average of 3ndash8

In the USA 20 million

school days are lost per

annum

Probiotics reduce risk of URTI episodes

8

01 02 05 1 2

Favours probiotic Favours control

RR (95 CI)

Additional findings

Reduced use of antibiotics ( 33) Reduced risk of 3 or more URTI episodes ( 47)

study in children

^ study in marathon

runners

Overall RR = 058

( 42)

Identified 27 clinical trials 10 used for meta-analysis

Hao et al 2011 Cochrane Library 9

Probiotics and respiratory

infections

Berggren et al (2011) Eur J Nutr 50 203-210

Probiotic Lactplantarum HEAL9

Lactparacasei 87002

1 x 109 d

Target group Healthy adults (272) aged 18-65

Study design Double blind randomized placebo

controlled parallel study 12 weeks

Outcome markers Incidence duration and severity of

respiratory infections

Probiotics amp Colds

10

Control Probiotic

Duration of episode 86d 62d (Plt005)

Symptom score 444 336 (NS)

Berggren et al

EJN 2011

Probiotics and ADeczema

bull Prevalence of atopic dermatitis (AD) has risen over the

past decades especially in western societies Now 10-

20

bull 7 trials on prevention amp 12 trials on treatment

bull No consistent effects Van de Aa et al 2009 Boyle et al 2009

bull But some studies show certain strains are effective

11

Probiotics amp critically ill patients

Systematic review of 23 RPC trials in critically ill patients

bull Probiotics associated with reductions in

ndash Infectious complications RR 082 (95CI 069-089)

ndash Ventilator assoc pneumonia RR 075 (059-097)

ndash ICU mortality (trend) RR 080 (059-109)

bull No effect on length of stay in ICU or hospital

bull Clinical and statistical heterogeneity noted

Petrof et al Crit Care Med 40 3290 (2012)

NB Severe acute pancreatitis study showed probiotics associated with

increased mortality (bowel ischaemia) (Besselink et al Lancet 371 651-

9 2008)

12

13

Probiotics in elective surgery

bull Meta-analysis of 13 RPCTs (n=962) with preoperative

probiotics and synbiotics in patients undergoing elective

general surgical procedures

bull Incidence of postoperative sepsis was reduced

bull probiotic group OR= 042 95 CI 023-075 P = 003

bull synbiotic group OR = 025 95 CI 01-06 P = 002

bull No reduction in the incidence of pneumonia urinary tract

infections or wound infections in the postoperative phase

bull Synbiotics reduced the length of postoperative antibiotic

use (P = 003) Kinross et alJParenter Enteral Nutr 2013 37(2)243-53

Probiotics and gut health

Probiotics and gut health

bull Antibiotic associated diarrhoea (AAD)

bull Clostridium difficile (C diff)

bull Helicobacter pylori

bull Irritable bowel syndrome (IBS)

bull Acute infectious diarrhoea

bull Necrotizing enterocolitis (NEC)

bull Pouchitis

bull Travelers diarrhoea

bull Lactose maldigestion

bull Constipation

bull Colorectal cancer

bull Colic in infants

bull Inflammatory bowel conditions (UC CD)

15

Meta analysis

Probiotics reduce incidence

of many gut disorders ndash meta-analysis

16

RR (95 CI)

01 02 05 1 2 5

Favours probiotic Favours control

Ritchie ampRomanuk Plos1 7 2012

Overall RR = 058

( 42)

AAD

C difficile

H pylori

IBS

Infdiarrhoea

NEC

Pouchitis

Trav

diarrhoea

Total

043 (032-056)

059 (041-086)

066 (054-091)

077 (065-092)

035 (013-087)

039 (024-063)

017 (010-030)

092 (079-105)

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 8: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Probiotics reduce risk of URTI episodes

8

01 02 05 1 2

Favours probiotic Favours control

RR (95 CI)

Additional findings

Reduced use of antibiotics ( 33) Reduced risk of 3 or more URTI episodes ( 47)

study in children

^ study in marathon

runners

Overall RR = 058

( 42)

Identified 27 clinical trials 10 used for meta-analysis

Hao et al 2011 Cochrane Library 9

Probiotics and respiratory

infections

Berggren et al (2011) Eur J Nutr 50 203-210

Probiotic Lactplantarum HEAL9

Lactparacasei 87002

1 x 109 d

Target group Healthy adults (272) aged 18-65

Study design Double blind randomized placebo

controlled parallel study 12 weeks

Outcome markers Incidence duration and severity of

respiratory infections

Probiotics amp Colds

10

Control Probiotic

Duration of episode 86d 62d (Plt005)

Symptom score 444 336 (NS)

Berggren et al

EJN 2011

Probiotics and ADeczema

bull Prevalence of atopic dermatitis (AD) has risen over the

past decades especially in western societies Now 10-

20

bull 7 trials on prevention amp 12 trials on treatment

bull No consistent effects Van de Aa et al 2009 Boyle et al 2009

bull But some studies show certain strains are effective

11

Probiotics amp critically ill patients

Systematic review of 23 RPC trials in critically ill patients

bull Probiotics associated with reductions in

ndash Infectious complications RR 082 (95CI 069-089)

ndash Ventilator assoc pneumonia RR 075 (059-097)

ndash ICU mortality (trend) RR 080 (059-109)

bull No effect on length of stay in ICU or hospital

bull Clinical and statistical heterogeneity noted

Petrof et al Crit Care Med 40 3290 (2012)

NB Severe acute pancreatitis study showed probiotics associated with

increased mortality (bowel ischaemia) (Besselink et al Lancet 371 651-

9 2008)

12

13

Probiotics in elective surgery

bull Meta-analysis of 13 RPCTs (n=962) with preoperative

probiotics and synbiotics in patients undergoing elective

general surgical procedures

bull Incidence of postoperative sepsis was reduced

bull probiotic group OR= 042 95 CI 023-075 P = 003

bull synbiotic group OR = 025 95 CI 01-06 P = 002

bull No reduction in the incidence of pneumonia urinary tract

infections or wound infections in the postoperative phase

bull Synbiotics reduced the length of postoperative antibiotic

use (P = 003) Kinross et alJParenter Enteral Nutr 2013 37(2)243-53

Probiotics and gut health

Probiotics and gut health

bull Antibiotic associated diarrhoea (AAD)

bull Clostridium difficile (C diff)

bull Helicobacter pylori

bull Irritable bowel syndrome (IBS)

bull Acute infectious diarrhoea

bull Necrotizing enterocolitis (NEC)

bull Pouchitis

bull Travelers diarrhoea

bull Lactose maldigestion

bull Constipation

bull Colorectal cancer

bull Colic in infants

bull Inflammatory bowel conditions (UC CD)

15

Meta analysis

Probiotics reduce incidence

of many gut disorders ndash meta-analysis

16

RR (95 CI)

01 02 05 1 2 5

Favours probiotic Favours control

Ritchie ampRomanuk Plos1 7 2012

Overall RR = 058

( 42)

AAD

C difficile

H pylori

IBS

Infdiarrhoea

NEC

Pouchitis

Trav

diarrhoea

Total

043 (032-056)

059 (041-086)

066 (054-091)

077 (065-092)

035 (013-087)

039 (024-063)

017 (010-030)

092 (079-105)

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 9: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Probiotics and respiratory

infections

Berggren et al (2011) Eur J Nutr 50 203-210

Probiotic Lactplantarum HEAL9

Lactparacasei 87002

1 x 109 d

Target group Healthy adults (272) aged 18-65

Study design Double blind randomized placebo

controlled parallel study 12 weeks

Outcome markers Incidence duration and severity of

respiratory infections

Probiotics amp Colds

10

Control Probiotic

Duration of episode 86d 62d (Plt005)

Symptom score 444 336 (NS)

Berggren et al

EJN 2011

Probiotics and ADeczema

bull Prevalence of atopic dermatitis (AD) has risen over the

past decades especially in western societies Now 10-

20

bull 7 trials on prevention amp 12 trials on treatment

bull No consistent effects Van de Aa et al 2009 Boyle et al 2009

bull But some studies show certain strains are effective

11

Probiotics amp critically ill patients

Systematic review of 23 RPC trials in critically ill patients

bull Probiotics associated with reductions in

ndash Infectious complications RR 082 (95CI 069-089)

ndash Ventilator assoc pneumonia RR 075 (059-097)

ndash ICU mortality (trend) RR 080 (059-109)

bull No effect on length of stay in ICU or hospital

bull Clinical and statistical heterogeneity noted

Petrof et al Crit Care Med 40 3290 (2012)

NB Severe acute pancreatitis study showed probiotics associated with

increased mortality (bowel ischaemia) (Besselink et al Lancet 371 651-

9 2008)

12

13

Probiotics in elective surgery

bull Meta-analysis of 13 RPCTs (n=962) with preoperative

probiotics and synbiotics in patients undergoing elective

general surgical procedures

bull Incidence of postoperative sepsis was reduced

bull probiotic group OR= 042 95 CI 023-075 P = 003

bull synbiotic group OR = 025 95 CI 01-06 P = 002

bull No reduction in the incidence of pneumonia urinary tract

infections or wound infections in the postoperative phase

bull Synbiotics reduced the length of postoperative antibiotic

use (P = 003) Kinross et alJParenter Enteral Nutr 2013 37(2)243-53

Probiotics and gut health

Probiotics and gut health

bull Antibiotic associated diarrhoea (AAD)

bull Clostridium difficile (C diff)

bull Helicobacter pylori

bull Irritable bowel syndrome (IBS)

bull Acute infectious diarrhoea

bull Necrotizing enterocolitis (NEC)

bull Pouchitis

bull Travelers diarrhoea

bull Lactose maldigestion

bull Constipation

bull Colorectal cancer

bull Colic in infants

bull Inflammatory bowel conditions (UC CD)

15

Meta analysis

Probiotics reduce incidence

of many gut disorders ndash meta-analysis

16

RR (95 CI)

01 02 05 1 2 5

Favours probiotic Favours control

Ritchie ampRomanuk Plos1 7 2012

Overall RR = 058

( 42)

AAD

C difficile

H pylori

IBS

Infdiarrhoea

NEC

Pouchitis

Trav

diarrhoea

Total

043 (032-056)

059 (041-086)

066 (054-091)

077 (065-092)

035 (013-087)

039 (024-063)

017 (010-030)

092 (079-105)

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 10: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Probiotics amp Colds

10

Control Probiotic

Duration of episode 86d 62d (Plt005)

Symptom score 444 336 (NS)

Berggren et al

EJN 2011

Probiotics and ADeczema

bull Prevalence of atopic dermatitis (AD) has risen over the

past decades especially in western societies Now 10-

20

bull 7 trials on prevention amp 12 trials on treatment

bull No consistent effects Van de Aa et al 2009 Boyle et al 2009

bull But some studies show certain strains are effective

11

Probiotics amp critically ill patients

Systematic review of 23 RPC trials in critically ill patients

bull Probiotics associated with reductions in

ndash Infectious complications RR 082 (95CI 069-089)

ndash Ventilator assoc pneumonia RR 075 (059-097)

ndash ICU mortality (trend) RR 080 (059-109)

bull No effect on length of stay in ICU or hospital

bull Clinical and statistical heterogeneity noted

Petrof et al Crit Care Med 40 3290 (2012)

NB Severe acute pancreatitis study showed probiotics associated with

increased mortality (bowel ischaemia) (Besselink et al Lancet 371 651-

9 2008)

12

13

Probiotics in elective surgery

bull Meta-analysis of 13 RPCTs (n=962) with preoperative

probiotics and synbiotics in patients undergoing elective

general surgical procedures

bull Incidence of postoperative sepsis was reduced

bull probiotic group OR= 042 95 CI 023-075 P = 003

bull synbiotic group OR = 025 95 CI 01-06 P = 002

bull No reduction in the incidence of pneumonia urinary tract

infections or wound infections in the postoperative phase

bull Synbiotics reduced the length of postoperative antibiotic

use (P = 003) Kinross et alJParenter Enteral Nutr 2013 37(2)243-53

Probiotics and gut health

Probiotics and gut health

bull Antibiotic associated diarrhoea (AAD)

bull Clostridium difficile (C diff)

bull Helicobacter pylori

bull Irritable bowel syndrome (IBS)

bull Acute infectious diarrhoea

bull Necrotizing enterocolitis (NEC)

bull Pouchitis

bull Travelers diarrhoea

bull Lactose maldigestion

bull Constipation

bull Colorectal cancer

bull Colic in infants

bull Inflammatory bowel conditions (UC CD)

15

Meta analysis

Probiotics reduce incidence

of many gut disorders ndash meta-analysis

16

RR (95 CI)

01 02 05 1 2 5

Favours probiotic Favours control

Ritchie ampRomanuk Plos1 7 2012

Overall RR = 058

( 42)

AAD

C difficile

H pylori

IBS

Infdiarrhoea

NEC

Pouchitis

Trav

diarrhoea

Total

043 (032-056)

059 (041-086)

066 (054-091)

077 (065-092)

035 (013-087)

039 (024-063)

017 (010-030)

092 (079-105)

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 11: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Probiotics and ADeczema

bull Prevalence of atopic dermatitis (AD) has risen over the

past decades especially in western societies Now 10-

20

bull 7 trials on prevention amp 12 trials on treatment

bull No consistent effects Van de Aa et al 2009 Boyle et al 2009

bull But some studies show certain strains are effective

11

Probiotics amp critically ill patients

Systematic review of 23 RPC trials in critically ill patients

bull Probiotics associated with reductions in

ndash Infectious complications RR 082 (95CI 069-089)

ndash Ventilator assoc pneumonia RR 075 (059-097)

ndash ICU mortality (trend) RR 080 (059-109)

bull No effect on length of stay in ICU or hospital

bull Clinical and statistical heterogeneity noted

Petrof et al Crit Care Med 40 3290 (2012)

NB Severe acute pancreatitis study showed probiotics associated with

increased mortality (bowel ischaemia) (Besselink et al Lancet 371 651-

9 2008)

12

13

Probiotics in elective surgery

bull Meta-analysis of 13 RPCTs (n=962) with preoperative

probiotics and synbiotics in patients undergoing elective

general surgical procedures

bull Incidence of postoperative sepsis was reduced

bull probiotic group OR= 042 95 CI 023-075 P = 003

bull synbiotic group OR = 025 95 CI 01-06 P = 002

bull No reduction in the incidence of pneumonia urinary tract

infections or wound infections in the postoperative phase

bull Synbiotics reduced the length of postoperative antibiotic

use (P = 003) Kinross et alJParenter Enteral Nutr 2013 37(2)243-53

Probiotics and gut health

Probiotics and gut health

bull Antibiotic associated diarrhoea (AAD)

bull Clostridium difficile (C diff)

bull Helicobacter pylori

bull Irritable bowel syndrome (IBS)

bull Acute infectious diarrhoea

bull Necrotizing enterocolitis (NEC)

bull Pouchitis

bull Travelers diarrhoea

bull Lactose maldigestion

bull Constipation

bull Colorectal cancer

bull Colic in infants

bull Inflammatory bowel conditions (UC CD)

15

Meta analysis

Probiotics reduce incidence

of many gut disorders ndash meta-analysis

16

RR (95 CI)

01 02 05 1 2 5

Favours probiotic Favours control

Ritchie ampRomanuk Plos1 7 2012

Overall RR = 058

( 42)

AAD

C difficile

H pylori

IBS

Infdiarrhoea

NEC

Pouchitis

Trav

diarrhoea

Total

043 (032-056)

059 (041-086)

066 (054-091)

077 (065-092)

035 (013-087)

039 (024-063)

017 (010-030)

092 (079-105)

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 12: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Probiotics amp critically ill patients

Systematic review of 23 RPC trials in critically ill patients

bull Probiotics associated with reductions in

ndash Infectious complications RR 082 (95CI 069-089)

ndash Ventilator assoc pneumonia RR 075 (059-097)

ndash ICU mortality (trend) RR 080 (059-109)

bull No effect on length of stay in ICU or hospital

bull Clinical and statistical heterogeneity noted

Petrof et al Crit Care Med 40 3290 (2012)

NB Severe acute pancreatitis study showed probiotics associated with

increased mortality (bowel ischaemia) (Besselink et al Lancet 371 651-

9 2008)

12

13

Probiotics in elective surgery

bull Meta-analysis of 13 RPCTs (n=962) with preoperative

probiotics and synbiotics in patients undergoing elective

general surgical procedures

bull Incidence of postoperative sepsis was reduced

bull probiotic group OR= 042 95 CI 023-075 P = 003

bull synbiotic group OR = 025 95 CI 01-06 P = 002

bull No reduction in the incidence of pneumonia urinary tract

infections or wound infections in the postoperative phase

bull Synbiotics reduced the length of postoperative antibiotic

use (P = 003) Kinross et alJParenter Enteral Nutr 2013 37(2)243-53

Probiotics and gut health

Probiotics and gut health

bull Antibiotic associated diarrhoea (AAD)

bull Clostridium difficile (C diff)

bull Helicobacter pylori

bull Irritable bowel syndrome (IBS)

bull Acute infectious diarrhoea

bull Necrotizing enterocolitis (NEC)

bull Pouchitis

bull Travelers diarrhoea

bull Lactose maldigestion

bull Constipation

bull Colorectal cancer

bull Colic in infants

bull Inflammatory bowel conditions (UC CD)

15

Meta analysis

Probiotics reduce incidence

of many gut disorders ndash meta-analysis

16

RR (95 CI)

01 02 05 1 2 5

Favours probiotic Favours control

Ritchie ampRomanuk Plos1 7 2012

Overall RR = 058

( 42)

AAD

C difficile

H pylori

IBS

Infdiarrhoea

NEC

Pouchitis

Trav

diarrhoea

Total

043 (032-056)

059 (041-086)

066 (054-091)

077 (065-092)

035 (013-087)

039 (024-063)

017 (010-030)

092 (079-105)

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 13: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

13

Probiotics in elective surgery

bull Meta-analysis of 13 RPCTs (n=962) with preoperative

probiotics and synbiotics in patients undergoing elective

general surgical procedures

bull Incidence of postoperative sepsis was reduced

bull probiotic group OR= 042 95 CI 023-075 P = 003

bull synbiotic group OR = 025 95 CI 01-06 P = 002

bull No reduction in the incidence of pneumonia urinary tract

infections or wound infections in the postoperative phase

bull Synbiotics reduced the length of postoperative antibiotic

use (P = 003) Kinross et alJParenter Enteral Nutr 2013 37(2)243-53

Probiotics and gut health

Probiotics and gut health

bull Antibiotic associated diarrhoea (AAD)

bull Clostridium difficile (C diff)

bull Helicobacter pylori

bull Irritable bowel syndrome (IBS)

bull Acute infectious diarrhoea

bull Necrotizing enterocolitis (NEC)

bull Pouchitis

bull Travelers diarrhoea

bull Lactose maldigestion

bull Constipation

bull Colorectal cancer

bull Colic in infants

bull Inflammatory bowel conditions (UC CD)

15

Meta analysis

Probiotics reduce incidence

of many gut disorders ndash meta-analysis

16

RR (95 CI)

01 02 05 1 2 5

Favours probiotic Favours control

Ritchie ampRomanuk Plos1 7 2012

Overall RR = 058

( 42)

AAD

C difficile

H pylori

IBS

Infdiarrhoea

NEC

Pouchitis

Trav

diarrhoea

Total

043 (032-056)

059 (041-086)

066 (054-091)

077 (065-092)

035 (013-087)

039 (024-063)

017 (010-030)

092 (079-105)

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 14: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Probiotics and gut health

Probiotics and gut health

bull Antibiotic associated diarrhoea (AAD)

bull Clostridium difficile (C diff)

bull Helicobacter pylori

bull Irritable bowel syndrome (IBS)

bull Acute infectious diarrhoea

bull Necrotizing enterocolitis (NEC)

bull Pouchitis

bull Travelers diarrhoea

bull Lactose maldigestion

bull Constipation

bull Colorectal cancer

bull Colic in infants

bull Inflammatory bowel conditions (UC CD)

15

Meta analysis

Probiotics reduce incidence

of many gut disorders ndash meta-analysis

16

RR (95 CI)

01 02 05 1 2 5

Favours probiotic Favours control

Ritchie ampRomanuk Plos1 7 2012

Overall RR = 058

( 42)

AAD

C difficile

H pylori

IBS

Infdiarrhoea

NEC

Pouchitis

Trav

diarrhoea

Total

043 (032-056)

059 (041-086)

066 (054-091)

077 (065-092)

035 (013-087)

039 (024-063)

017 (010-030)

092 (079-105)

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 15: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Probiotics and gut health

bull Antibiotic associated diarrhoea (AAD)

bull Clostridium difficile (C diff)

bull Helicobacter pylori

bull Irritable bowel syndrome (IBS)

bull Acute infectious diarrhoea

bull Necrotizing enterocolitis (NEC)

bull Pouchitis

bull Travelers diarrhoea

bull Lactose maldigestion

bull Constipation

bull Colorectal cancer

bull Colic in infants

bull Inflammatory bowel conditions (UC CD)

15

Meta analysis

Probiotics reduce incidence

of many gut disorders ndash meta-analysis

16

RR (95 CI)

01 02 05 1 2 5

Favours probiotic Favours control

Ritchie ampRomanuk Plos1 7 2012

Overall RR = 058

( 42)

AAD

C difficile

H pylori

IBS

Infdiarrhoea

NEC

Pouchitis

Trav

diarrhoea

Total

043 (032-056)

059 (041-086)

066 (054-091)

077 (065-092)

035 (013-087)

039 (024-063)

017 (010-030)

092 (079-105)

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 16: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Probiotics reduce incidence

of many gut disorders ndash meta-analysis

16

RR (95 CI)

01 02 05 1 2 5

Favours probiotic Favours control

Ritchie ampRomanuk Plos1 7 2012

Overall RR = 058

( 42)

AAD

C difficile

H pylori

IBS

Infdiarrhoea

NEC

Pouchitis

Trav

diarrhoea

Total

043 (032-056)

059 (041-086)

066 (054-091)

077 (065-092)

035 (013-087)

039 (024-063)

017 (010-030)

092 (079-105)

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 17: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Probiotics and AAD

bull Diarrhoea is common side effect of broad spectrum antibiotics in older people hospitals amp nursing homes

bull Frequency 10-60

bull Clostridium difficile implicated in 15-25 of AAD

AAD is one of the most well studied areas for probiotics

gt80 studies 4 meta-analyses children adults elderly RR = 043 - 058

Largest (Hempel et al 2012)

2563 studies showed sig reduction in risk overall 42

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 18: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

Probiotic Lactobacillus acidophilus CL1285

Lactobacillus casei Bio-K+ CL1285

Target group Hospitalised older individuals (89)

anticipated to be taking three days of

antibiotics

Study design 50 x 109in a fermented milk drink half-dose

for two days then once daily or placebo

during antibiotic treatment

Outcome markers Incidence of diarrhoea duration in hospital

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 19: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Beausoleilet al (2007) Can J Gastroenterol21

732

Probiotics and AAD

plt005

plt006

P=015

Placebo

Probiotic

No

patients

days d

ura

tion

AAD CDiff Mean

hospitalisation

36

16

34

16

23

RR=034 RR=013

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 20: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

bull Common gut complaint - around 20 prevalence

bull May be related to imbalances in gut microbiota - aetiology remains unclear

Irritable Bowel Syndrome - IBS

Identified by symptoms (bloating abdominal pain diarrhoea constipation)

bull 2 meta-analyses bull RR= 077

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 21: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

IBS Meta-analysis

McFarland amp Dublin (2008) World J Gastroenterol 14 2650

Nobaek 2000 L plantarum

Niedzielin 2001 L plantarum

Whorwell 2006 B infantis1010

Enck 2007 E coli + Strep faecalis

Maupas 1983 S boulardii

Gade 1989 Strep faecalis

Halpern 1996 L acidophilus

Kim 2003 VSL3

Kajander 2005 Mixture

Simren 2006 L plantarum

Whorwell 2006 B infantis106

Whorwell 2006 B infantis108

Marteau 2007 Mix

Simren 2007 Mix

Overall 077 (062 094) 100

00234 1 427

Favours probiotic Favours placebo

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 22: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotic B bifidum MIMBb75

Target group IBS patients (122) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Randomised double-blind placebo-

controlled Daily 1 x 109 freeze-dried in

capsules Two week run-in four week

feeding two week washout

Outcome markers Global symptom assessment on 7-point

Likert scale

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 23: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

Global IBS scores (0-6 scale)

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 24: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

35

30

25

20

15

1 2 3 4 5 6 7 8

Week

Sym

pto

m s

core

Placebo

B bifidum MIMBb75

bull Pain and discomfort

bull Likert 0-6 scale

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics and IBS

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 25: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

0

10

20

30

40

50

Week 6 Week 8

8 11

48 47

B bifidum MIMBb75

Placebo bull Adequate relief after treatment

bull Week 6 post treatment week 8 post washout

Probiotics and IBS

Guglielmetti et al (2011) Aliment Pharmacol Ther 33

1123

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 26: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Probiotics amp IBS

Probiotic Bifidobacteriumanimalis DN-173 010

Target group Women with IBS-C (34) age gtc40

Study design 1 x 1010 yoghurt twice daily placebo 4

weeks

Outcome markers Quality of life and digestive discomfort

scores bloating

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 27: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Overall

IBS

Abdominal

pain Flatulence Bloating

Score

4

3

2

Irritable Bowel Syndrome

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 28: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Bloating

1 2 3 4 5 6 7 8 9 10 11 12 13 0

1

2

3

4

5

Hours

cm

Abdominal inductance plethysmography

Placebo

Probiotic

Agrawalet al (2009) Aliment Pharmacol Ther29

104

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 29: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

NEC

Necrotizing enterocolitis (NEC)

associated with increased morbidity

and mortality in preterm infants

(lt15kg)

Incidence 7-14 Mortality up to 50

Causes immature gutimmune

system abnormal microflora

29

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 30: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Probiotics and NEC

Cochrane review amp meta-analysis

bull 16 eligible studies on LBW infants (n=2842) in hospitals

bull Enteral probiotics supplementation significantly reduced

auml Incidence of severe NEC (stage II-III)

RR= 035 (95 CI 024-052)

auml MortalityRR =040 (95CI 027-060)

auml Effective strains ndashL acidophilus LGG B infantis B

infantis+Bbifidum+ Strep thermophilus

(Alfaleh et al Cochrane Database Syst Rev 2011 Mar 16(3)CD005496)

30

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 31: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Prebiotics

31

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 32: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

What is a prebiotic

A selectively fermented ingredient that allows

specific changes both in the composition

andor activity in the gastrointestinal microbiota

thus conferring benefit on host health

Gibson GR Probert HM Van Loo J Rastall RA ampRoberfroid MB (2004) Dietary modulation of the human

colonic microbiota updating the concept of prebiotics Nutr Res Rev17 259-75

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 33: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Non-digestible oligosaccharides (NDO)

bull Low molecular weight carbohydrates DP 2 ndash 10

bull Occur in plants (chicory asparagus artichoke onions garlic soy)

and human breast milk

bull Synthesizedextracted for supplements

ndash Inulin

ndash Fructo-oligosaccharides (FOS)

ndash Galacto-oligosaccharides (GOS)

ndash Lactulose

ndash Soybean oligosaccharides

ndash Xylo-oligosaccharides (XOS)

ndash Isomalto-oligosaccharides (IMO)

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 34: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TD AAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 35: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Claimed health benefits of prebiotics

Modify colon flora

Laxation

Lipid metabolism Diarrhoea

(TDAAD)

Colon cancer

Mineral absorption

IBSIBD

Immune func Infectionsallergy

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 36: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Travellersrsquo Diarrhoea

Cummings et al AlimPharmTher 15 1139 (2001) 244 subjects given 10g FOS or placebo 2 wk

before visiting high risk destination

TD incidence Placebo 19 FOS 12 (P=008)

Drakoularakou et al Eur J Clin Nutr 64146 (2010)

160 volunteers travelling for at least 2 weeks to high or

low risk countries

TD incidence Placebo 39 GOS 25 (Plt005)

TD duration Placebo 46d GOS 24d (Plt005)

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 37: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Prebiotics amp immune function

infant formulas

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 38: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Prebiotics and atopic dermatitis

in infants

bull RDBPC trial 206 infants 11+-9d old

bull Basic formula hydrolysed cowrsquos milk whey (hypoallergenic)

bull Placebo 08g100ml maltodextrin

bull Prebiotic 08g100ml (90 GOS10 FOS)

bull Atopic dermatitis and infections monitored for 6-24 months

Moro et al Arch Dis Child 91 814 2006

Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 39: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Effect of prebiotic infant formula

on atopic dermatitis

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS

91) or control (08 maltodextrin) for 6 mo Follow up at 18-24 mo

(Moro et al Arch Dis Child 91 814 2006 Arslanoglu et al J Nutr 138 1091ndash1095 2008

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 40: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Effect prebiotic infant formula

on infections at 2 years

Infants at risk of atopic disease given prebiotic formula (08 GOSlcFOS 91) or control (08 maltodextrin) for 6 mo Data shown for follow up at 18-24 mo N=6866 Plt005 Plt001 Plt00001

Arslanogluet al J Nutr 138 1091-5 2008

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 41: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Prebiotics amp Ca absorption

in adolescents

bull 95 mampf adolescents 9-13y

bull 8gd Synergy (FOSinulin) or maltodextrin for 1 y

Placebo (n=48) FOS (n=47)

Ca absorption 317 377 (stable isotope)

∆ BMC g 210 245

∆ BMD gcm2 0032 0047

(whole body)

Sig different from placebo Plt005 Plt001

Abrams et al AJCN 82 471 (2005)

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 42: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

42

Pro- pre-biotics and cancer risk

- cell proliferation in biopsies

12 wk intervention in resected polyp patients 1 Placebo Maltodextrin (sachet + capsule) 2 Probiotics LGG (1010d) B lactis BB12 (1010d) plus Prebiotic FOS12gd) Plt005 vs 0 wk (Rafter et al AJCN 85488 )

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 43: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

PREBIOTICS amp

IRRITABLE

BOWEL SYNDROME

43

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 44: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Prebiotics and IBS

Prebiotic B bifidumndashsynthesised GOS (Bimuno)

Target group IBS (DCA) patients (44) aged 18-65 with

mild to moderate IBS (Rome II)

Study design Randomised double-blind placebo-

controlled 14 gday or 275gday Bimuno

or placebo 12 week treatment

Outcome markers Global symptom assessment on 7-point

Likert scale subjective global assessment

QOL assessment and microbiological

evaluation

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 45: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Prebiotics and IBS

Silk et al (2009) Aliment

Pharmacol Ther29 508-518

Flatulence Bloating Likert scale SGA

0

1

2

3

4

5

-1

-2

-3

Impro

vem

ent

from

sta

rt o

f stu

dy

dagger

dagger significantly different from the start

significantly different from the start and the placebo

B-GOS (137gday)

Placebo

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 46: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

bullLow FODMAP diet aims to reduce fermentable

carbohydrates in the diet to regulate gas production

bullFermentable carbohydrates identified in several

groups

Fermentable

Oligosaccharides

Disaccharides

Monosaccharides

And

Polyols

Prebiotics and the low FODMAP diet

Fructans

Galactooligosaccharides

Lactose

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 47: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Intervention FODMAP diet versus control

Target group IBS patients (41) aged 18-65 with mild to

moderate IBS (Rome III)

Study design Control diet or fermentable carbohydrate-

restricted diet for 4 weeks

Outcome markers Incidence and severity of symptoms

Faecal bacteriology

Staudacheret al (2012) J Nutr142 1510

Prebiotics and the low FODMAP diet

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 48: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Prebiotics and the low FODMAP diet

90

80

70

60

50

40

30

20

10

0

Control diet

Low FODMAP diet

Pro

port

ion o

f patients

(

)

Staudacheret al (2012) J Nutr142 1510

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 49: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Conclusions -Probiotics

bull There is a large number of human trials and a lot

of sound science to support biological effects and

health benefits of probiotics

bull Probiotics are not effective in all areas of health

bull Best evidence comes from studies on immune

function and gut health

bull For some health endpoints meta-analyses

indicate that beneficial effects are common to

many probiotics but in some cases effects are

species- and even strain- specific

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk

Page 50: Probiotics & prebiotics in disease - Irspen · Probiotics & prebiotics in disease - relevance for clinical practice Ian Rowland ... Probiotic Lactobacillus acidophilus CL1285 Lactobacillus

Conclusions - Prebiotics

bull Fewer human studies than probiotics

bull RCTs indicate beneficial effects on

bull Travellerrsquos diarrhoea amp AAD recurrence

bull Ca absorption in adolescents

bull Atopic dermatitis amp infections in infants

bull IBS (but not consistent with FODMAP)

bull Microbiota modulation

bull Emerging evidence for reduction in cancer risk


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