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 Mood Anxiety Improved Natural Killer cell function Improved phagocyte function Adjuvant effects Improved barrier function Pouchitis Salmonellosis Bacteriocin production Improved microecology Gut/Brain Axis Reduced antibiotic use Immune Th1/Th2 balance Gut Function Treg function Otitis E. coli media O157 - H7 Respiratory infections Low gut ph Antiinflammatory Crohn s Ulcerative colitis disease Traveller s Anxiety diarrhoea Obesity Diabetes Anti-infection NEC Metabolic Syndrome IBS Probiotics Constipation Gut Comfort Bloating Anti-IBD Intestinal pain Gut transit time Anti- Diarrhoea Anti- Allergy Growth/Nutrition Lactose intolerance Rotaviral infection Antibioticassociated diarrhoea Immune programming Eczema Hay fever Iron status Bone health Improved suboptimal growth
Fonterra probiotics
Fonterra probiotics Bifidobacterium animalis subsp. lactis HN019 (DR10 ) Lactobacillus rhamnosus HN001 (DR20 ) 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 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
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 administered in adequate amounts, Ideal Probiotic 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 HN019+GOS (n=312) Control (n=312) OR (95% CI) p value 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 Sazawal et al (2010), PLOS One, 5:e12164 * ALRI = acute lower respiratory infection
HN019+GOS improved iron status % 60 50 HN019+GOS (n=230) Control (n=213) 40 p = 0.08 30 20 p = 0.09 p = 0.01 * 10 0 Anaemic Iron deficient Anaemic and 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 dosedependent 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: 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% *p<0.05 p<0.01 p<0.001 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% 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 Period Placebo HN019 40 % Eczema HN001 20 0 0 2 4 6 Year Wickens et al, Clin Exp Allergy, 2013, 43:1048-1057
Stability
Stability 34 Storage temp. ( C) 32 30 28 HN019 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?
Conclusions 2 All probiotics are not equal! Specific probiotic strains have specific health benefits Same species, different properties...