Host Institution
Fonterra Probiotics: From guts to glory… James Dekker April 16, 2015
Probiotic bacteria
“Live micro-organisms which, when
administered in adequate amounts,
confer a health benefit on the host”
FAO/WHO Report (2001)
3
Why work on Probiotic bacteria?
Part of the human diet for millennia
Hygiene hypothesis / “old friends” hypothesis
Health benefits delivered via a food
Strong synergy with dairy fermentations
Probiotics currently worth NZ$ 54 Billion* (supplements, yoghurts, juice)
Expected to grown to NZ$ 73 Billion* by 2020
Probiotic infant formula to claim 76% Share of NZ$ 33 Billion market in 2024
* Euromoniter data, 2016
Some published health effects of probiotic bacteria…
Anti-IBD
Anti-
Ulcerative colitis disease Traveller’s
diarrhoea
Antibiotic- associated diarrhoea
Rotaviral infection
Immune
Improved Natural Killer cell function
Improved phagocyte
function
Adjuvant effects
Reduced antibiotic use
Th1/Th2
Comfort
Constipation
Bloating
Gut transit time
Intestinal pain
Anti- Allergy
Immune programming
Eczema
Hay fever
Growth/Nutrition
Otitis media
Salmonellosis
E. coli
Improved barrier function
Pouchitis
Bacteriocin production
Metabolic Syndrome
Function
Improved microecology
Iron status
Improved sub- optimal growth
IBS
Probiotics
Diarrhoea
Crohn’s
Immune
Treg function
balance
Gut Comfort
Constipation
Bloating
Gut transit time
Eczema
Hay fever
Growth/Nutrition Anti-infection
Salmonellosis
E. coli O157 - H7
Low gut pH
Lactose intolerance
Pouchitis
Bacteriocin production
Gut
Bone health IBS
NEC
Respiratory infections
Anxiety Diabetes
Anti-inflammatory
Obesity
Gut/Brain Axis
Mood
Anxiety
Fonterra probiotics
Fonterra probiotics
Bifidobacterium animalis subsp. lactis HN019 (DR10™)
Lactobacillus rhamnosus HN001 (DR20™)
• Demonstrated efficacy: • Immune protection & gut health benefits • Anti-pathogen effects (in animal models) • Improved colonic transit time in adults
(HN019) • Protects against respiratory disease in infants
(HN019) • Protects against eczema in infants (HN001)
• Halal & Kosher certified
• Patent Protected
• Well researched strains: • 70+ peer-reviewed publications • Health benefits in healthy
populations • Established safety record
• Stability/Applications
• Superior long-term survival in dry powders
• Reduced cost-in-use • Demonstrated survival of gut transit
Probiotic bacteria
“Live micro-organisms which, when
administered in adequate amounts,
confer a health benefit on the host”
FAO/WHO Report (2001)
• An ideal probiotic must be shown to be:
– Safe – show no adverse effects on the host
– Stable – reach the consumer in a live state and survive in the human gastrointestinal tract
– Effective – provide a positive health benefit to the host
Efficacy Safety
Stability
Ideal Probiotic
Safety
Safety HN019 HN001
Food origin Strain identification Do not activate platelets Do not degrade mucin No abnormal antibiotic resistance Lack of toxicity in animal models Do not exacerbate autoimmune disease Published genome sequence Not associated with adverse events in humans US FDA-notified GRAS
Efficacy
Immune biomarker studies
Natural Killer (NK) Cells Phagocytic cells
• NK cell activity and phagocytosis play vital “surveillance” roles, recognising pathogens & alerting the rest of the immune system
• When fed to humans, both HN019 and HN001 improved NK cell and phagocyte activity
• So what…?
Bifidobacterium animalis subsp. lactis HN019
“India trial”, HN019+GOS childhood morbidity trial
• Community-based, randomised, double-blind and placebo controlled study conducted by Prof Sunil Sazawal (Johns Hopkins University)
• Conducted at Sangam Vihar, New Delhi, India.
• Participants were 634 healthy children aged 1-3 years old, randomised to:
• Control group = fortified reconstituted milk
• Synbiotic group = fortified reconstituted milk with:
» HN019 (1.9X107 CFU/day)
» galactooligosaccharide (GOS) (2.4 g/day)
• Intervention period = daily for 12 months, with 12 month follow-up
• Incidence of early childhood morbidities, and parameters of growth and development monitored by trained medical personnel
HN019/GOS reduced measures of childhood illness
No. of episodes OR (95% CI) p value HN019+GOS
(n=312) Control (n=312)
Gastrointestinal morbidity Diarrhoea episodes (1–4 y) 1641 1697 0.94 (0.88–1.01) 0.08
≤ 2 years mo 603 563 0.99 (0.89–1.11) 0.91
> 2 years 1038 1134 0.90 (0.83–0.98) 0.02
Dysentery episodes 125 154 0.79 (0.62–1.00) 0.05
Respiratory morbidity Pneumonia episodes 90 115 0.76 (0.58–1.00) 0.05
Severe ALRI episodes* 34 51 0.65 (0.42–1.00) 0.05
Febrile illness and others Days with severe illness 473 550 0.84 (0.74–0.95) 0.004
Days with ear discharge 1550 1613 0.93 (0.87–1.00) 0.06
Days with high fever 2798 2865 0.95 (0.90–1.00) 0.05
Measles 5 10 0.49 (0.17–1.42) 0.19 Doses of antibiotics
consumed 7402 7625 0.94 (0.91–0.97) 0.001
* ALRI = acute lower respiratory infection Sazawal et al (2010), PLOS One, 5:e12164
HN019+GOS improved iron status
HN019+GOS (n=230) Control (n=213)
Sazawal et al (2010), J Pediatr Gastroenterol Nutr. 51:341-6.
*OR = 0.55, 95% CI = 0.35 – 0.89)
0
10
20
30
40
50
60
Anaemic Iron deficient
Anaemic and iron deficient
p = 0.09
p = 0.08
p = 0.01
%
*
Children in treatment group showed statistically significant improvement in general health parameters:
• Protection against respiratory disease (35%)
• Protection against dysentery (22%)
• Protection severe illnesses (non diarrhoeal) (16%)
• Protection against sickness with high temperature (febrile illness) (32%)
• Protection against ear infection (7%)
• Decreased antibiotic use (6%)
• Improved growth (growth rates closer to WHO standards)
• Clinically-meaningful reduction in iron deficiency anaemia
HN019 & GOS trial: Key findings
Sazawal et al (2010), PLOS One, 5:e12164; Sazawal et al (2010), J Pediatr Gastroenterol Nutr. 51:341-6
HN019 and colonic transit time (CTT) in healthy adults
• Average CTT for a healthy individual is 18 – 72 h • Variable or abnormal CTT is associated with
gastrointestinal ill-health, pain, or discomfort • Constipation is one of the most common digestive
complaints
• Placebo-controlled double-blind clinical trial on healthy adults with mild GI symptoms in USA
– Placebo control group (n=33) – High-dose HN019 (1010 CFU/day) (n=34) – Low=dose HN019 (109 CFU/day) (n=33)
• Subjects treated for 14 days • CTT assessed using radio-opaque beads • Also examined frequency of digestive
discomfort symptoms
Waller et al (2011) Scan. J. Gastro.
HN019 improved gut transit in a dose-dependent manner:
Treatment baseline CTT post-treatment CTT P value
High HN019 49 ± 30 h 21 ± 32 h <0.001
Low HN019 60 ± 33 h 41 ± 39 h 0.01
Placebo 43 ± 31 h 44 ± 33 h n.s.
Waller et al (2011) Scan. J. Gastro.
Change in Gastrointestinal Symptom Severity after 14 Days Supplementation with HN019 or Placebo:
Symptom
High Dose HN019 (n=33)
Low dose HN019 (n=26)
Placebo (n=29)
Vomiting - 17% * - 12% - 2%
Regurgitation - 24% * - 20% * - 5%
Gurgling - 16% * - 31% ‡ - 7%
Nausea - 23% † - 22% † - 7%
Abdominal pain - 27% † - 35% ‡ - 12%
Diarrhea - 6% 0% -17% * Flatulence - 15% * - 19% * - 8%
Constipation - 29% ‡ - 32% ‡ -15% * Irregular bowel movements - 20% † - 25% † - 11%
*p<0.05
†p<0.01
‡p<0.001
HN019 improved GI symptoms
Waller et al (2011) Scan. J. Gastro.
Lactobacillus rhamnosus HN001
“Wellington eczema trial”
• Double blind randomized placebo-controlled trial that examined the onset of eczema in infants at risk of allergic disease supplemented with HN001 (6x109 CFU/day), HN019 (9x109 CFU/day), or placebo
• Around 150 mothers/infants per group • Maternal supplementation = daily, from 35 weeks gestation
until 6 months if breastfeeding • Infant supplementation = daily, from birth until 2 years. • Primary outcome = onset of eczema
Effect of HN001 and HN019 on Eczema at 6 years
Placebo HN019 HN001
Treatment Period
0
20
40
60
0 2 4 6
% Eczema
Year
Cumulative eczema prevalence
Wickens et al, Clin Exp Allergy, 2013, 43:1048-1057
Stability
Stability
Water Activity
Storage temp.
(°C)
34 32 30 28 26 24
0.12 0.13 0.14 0.15 0.16 0.17 0.18 0.19 0.20 0.21 0.22
HN019
Probiotic “A”
(Indicative data only)
Conclusions 1 What is research for? • What can it do? What’s the health benefit?
• Is it safe? • Are you sure??? • Will it work in our products? At a cost-effective dose? • What do we have to show so that we can say what we are
allowed to say? • What is an acceptable level of proof? • How does it work? What’s the reason to believe? • New news = what can we say and when?
Conclusions 2
Same species, different properties...
• All probiotics are not equal!
• Specific probiotic strains have specific health benefits