Fonterra Probiotics: From guts to glory James Dekker April 16, 2015 - PowerPoint PPT Presentation

Fonterra Probiotics: From guts to glory… James Dekker April 16, 2015 Host Institution

Probiotic bacteria “Live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host” FAO/WHO Report (2001)

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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… Low gut pH Improved barrier Anti- Ulcerative function Crohn’s inflammatory Rotaviral colitis disease Traveller’s infection Anxiety Improved diarrhoea Diabetes microecology Gut Obesity Mood Function Anti-IBD Antibiotic- associated Metabolic Gut/Brain Axis Anxiety diarrhoea Anti- Syndrome Diarrhoea Improved Reduced antibiotic use Natural Killer cell function Immune programming Improved Immune Immune Probiotics Anti- phagocyte Eczema Eczema Allergy function Hay fever Hay fever Treg function Th1/Th2 Adjuvant balance effects Iron Growth/Nutrition Growth/Nutrition status Pouchitis Pouchitis Anti-infection Gut Intestinal Comfort Comfort Salmonellosis Salmonellosis pain Bone health IBS IBS NEC Bacteriocin Bacteriocin Lactose intolerance Improved sub- Otitis Bloating Bloating E. coli E. coli production production optimal growth media O157 - H7 Constipation Constipation Gut transit time Gut transit time Respiratory infections

Fonterra probiotics

Fonterra probiotics Bifidobacterium animalis subsp. lactis HN019 (DR10™) Lactobacillus rhamnosus HN001 (DR20™) • Demonstrated efficacy: • Well researched strains: Immune protection & gut health benefits • • 70+ peer-reviewed publications • Anti-pathogen effects (in animal models) Health benefits in healthy • populations • Improved colonic transit time in adults (HN019) • Established safety record • Protects against respiratory disease in infants (HN019) • Stability/Applications • Protects against eczema in infants (HN001) • Superior long-term survival in dry powders • Halal & Kosher certified • Reduced cost-in-use • Demonstrated survival of gut transit • Patent Protected

Probiotic bacteria • 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 “Live micro-organisms which, when Ideal Probiotic administered in adequate amounts, confer a health benefit on the host” Stability FAO/WHO Report (2001)

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 (1.9X10 7 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 Control (n=312) (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 60 HN019+GOS (n=230) % Control (n=213) 50 p = 0.08 40 30 p = 0.09 * p = 0.01 20 10 0 Anaemic Iron Anaemic and deficient iron deficient * OR = 0.55, 95% CI = 0.35 – 0.89) Sazawal et al (2010), J Pediatr Gastroenterol Nutr. 51:341-6.

HN019 & GOS trial: Key findings 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 Sazawal et al (2010), PLOS One, 5:e12164; Sazawal et al (2010), J Pediatr Gastroenterol Nutr. 51:341-6

HN019 for Gut Comfort It hurts!

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 (10 10 CFU/day) (n=34) – Low=dose HN019 (10 9 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.

HN019 improved GI symptoms Change in Gastrointestinal Symptom Severity after 14 Days Supplementation with HN019 or Placebo: High Dose HN019 Low dose HN019 Placebo Symptom (n=33) (n=26) (n=29) * p<0.05 Vomiting - 17% * - 12% - 2% † p<0.01 Regurgitation - 20% * - 24% * - 5% ‡ p<0.001 Gurgling - 16% * - 31% ‡ - 7% Nausea - 23% † - 22% † - 7% Abdominal pain - 27% † - 35% ‡ - 12% Diarrhea -17% * - 6% 0% Flatulence - 15% * - 19% * - 8% Constipation -15% * - 29% ‡ - 32% ‡ Irregular bowel - 20% † - 25% † - 11% movements 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 (6x10 9 CFU/day), HN019 (9x10 9 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 Cumulative eczema prevalence 60 Treatment Placebo Period HN019 40 HN001 % Eczema 20 0 0 2 4 6 Year Wickens et al, Clin Exp Allergy, 2013, 43 :1048-1057

Stability

Stability 34 32 Storage temp. 30 (°C) HN019 28 26 Probiotic “A” 24 0.12 0.13 0.14 0.15 0.16 0.17 0.18 0.19 0.20 0.21 0.22 Water Activity (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?