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

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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-

• ptimal 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

• thers

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)

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 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 (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

20 40 60 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