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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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