Developing the potential of prebiotics and probiotics as immune health ingredients

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1 Developing the potential of prebiotics and probiotics as immune health ingredients ARTHUR OUWEHAND ACTIVE NUTRITION DUPONT NUTRITION & HEALTH 20 th November 2014,

2 The gut microbiome The gut microbiota protects against enteropathogens, extracts nutrients and energy from our diets, and contributes to normal immune function Our bodies contain 37 trillion human cells - but 100 trillion bacterial cells! That s 100,000,000,000,000 microbes! The healthy gut microbiota is variable and influenced by: Diet Age Genetics Antibiotics Environment Immune System Stress Nutr. Rev. 70:S38-S44 2

3 Change in the environment and microbiota Hygiene hypothesis (Strachan 1989) Microbial Old Friends (Rook 2003) Microbial Diversity (Matricardi 2010, von Hertzen 2011) Von Hertzen 2009 Allergy 3

4 Microbiota has profound influence on health Gastrointestinal diseases/ dysbiosis / infections Functional disorders, irritable bowel syndrome Inflammatory bowel disease (Crohn s, Ulcerative Colitis) Antibiotic associated diarrhea, traveller s diarrhea, necrotizing enterocolitis Resistance to infections Allergic diseases Asthma, atopic dermatitis, eczema, rhinitis, foodand aeroallergies Ulcerative colitis UC CD Crohn s disease Qin et al., 2010 Healthy controls H Metabolic diseases Diabetes, obesity, atherosclerosis, metabolic syndrome, hepatic encephalopathy Autistic spectrum disorders 4

5 Immune defenses External defense Skin Mucous membranes Secretions Gut microbiota Second line of defense Innate immune cells (eg phagocytes) Antimicrobial proteins Inflammation & Fever Third line of defense Specific Immune cells (B cells, T cells) Antibodies against specific antigens (Immunoglobulins) Innate immunity Adaptive immunity 5

6 Levels of immune modulation by probiotics ijkers et al., 2010

7 Primed immune cells not always return to the same site Brandtzaeg et al. 1999

8 Respiratory tract infection in children 11/21/2014

9 Study design 26-week, prospective, double-blinded, placebo controlled study From November to May 326 children randomised over three treatments Children aged 3-5 years in a daycare center in Shanghai, China Dose: Daily, 5 x 10 9 CFU twice a day or placebo Control, n = 92 Lactobacillus acidophilus NCFM n = 77 HOWARU Protect (L. acidophilus NCFM + B. lactis Bi-07) n = 79 Week 0 26 Monitored: Symptoms of respiratory tract infection Gastrointestinal complaints Fever Antibiotic use Ref: G.Leyer et al; Pediatrics effects on cold and flu influenza like symptom incidence and duration; PEDIATRICS Vol. 124 No. 2 August 1, 2009

10 Days Days Protect Kids reduces number of days ill Days sick Missed daycare Placebo HOWARU Protect Ref: G.Leyer et al; Pediatrics effects on cold and flu influenza like symptom incidence and duration; PEDIATRICS Vol. 124 No. 2 August 1, 2009

11 In perspective 11

12 Protect Kids reduces symptoms of cold and antibiotic use Ref: G.Leyer et al; Pediatrics effects on cold and flu influenza like symptom incidence and duration; PEDIATRICS Vol. 124 No. 2 August 1, 2009

13 Effect of probiotics on RTI duration King et al. 2014

14 Respiratory tract infection in adults 11/21/2014

15 Study design Triple blind, randomised, placebo controled Age: 36 ± 12 years Physical activity: 8.3 ± 3.8 h/week Number of subjects 464 (Placebo=148, HP Adult=155, HP Sport=161) Study product: Placebo Microcrystaline cellulose HOWARU Protect Adult (B. lactis Bl-04) CFU/d HOWARU Protect Sport (L. acidophilus NCFM + B. lactis Bi-07) CFU/d Monitored: Physical activity Illness

16 Effect of HOWARU Protect consumption on time-to-illness HOWARU B. lactis Bl-04 Protect Sport HOWARU Protect Adult Placebo 50% Ref: Nicholas P. West et al; Clinical Nutrition; Probiotic supplementation for respiratory and gastrointestinal illness symptoms in healthy physically active individuals; Clinical Nutrition,

17 Protect adult lead to 27% total URTI risk reduction Ref: Nicholas P. West et al; Clinical Nutrition; Probiotic supplementation for respiratory and gastrointestinal illness symptoms in healthy physically active individuals; Clinical Nutrition, 2013.

18 ½ hour increase in weekly exercise Ref: Nicholas P. West et al; Clinical Nutrition; Probiotic supplementation for respiratory and gastrointestinal illness symptoms in healthy physically active individuals; Clinical Nutrition, 2013.

19 Reducing risk of atopic eczema 11/21/2014

20 BIRTH Study outline A PRENATAL & POSTNATAL TREATMENT 35 WEEKS PREGNANCY BETWEEN 2 &16 DAYS POSTBIRTH 6 MONTH POSTNATAL 2/4/6 YEARS AGE Mother Infant AIM OF THE STUDY To study the effect of prenatal and postnatal HOWARU rhamnosus or HOWARU Bifido supplementation on the infant s risk of developing atopy, allergy, and eczema. STUDY DESIGN 2-center, double-blind, randomized, placebo-controlled trial including 446 infants divided in 3 treatment groups. 1. Placebo (n=150) 2. HOWARU rhamnosus 6*10 9 per day (n=144) 3. HOWARU bifido - 9*10 9 per day (n=152) Eczema severity was evaluated by using SCORing Atopic Dermatitis (SCORAD) Wickens et al. 2008; Wickens et al. 2012; Wickens et al. 2013; 20

21 HN001 protects from allergic sensitization at 6 years Significant for aeroallergens (p=0.02), but not for food (p=0.60) Placebo HN019 HN001 HN001 had tendency to lower total IgE (p=0.07) Wickens et al. 2013

22 HN001 decreases risk for eczema and its severity Wickens et al. 2013

23 Probiotics and atopy prevention 11/21/2014 (Elazab et al. 2013) Favours probiotic Favours placebo

24 Prebiotics and atopy prevention (Mugambi et al. 2012)

25 Probiotics balance the immune system Immune suppression by probiotics Normal immune response Immune stimulation by probiotics 25

26 Conclusions Microbiota modulates the immune system Probiotics modulate the immune system: May improve resistance to infection (also outside the intestine) May reduce inflammation May reduce allergy risk 11/21/2014

27 11/21/2014 Copyright 2012 DuPont or its affiliates. All rights reserved. The DuPont Oval Logo, DuPont Danisco and all products denoted with or are registered trademarks or trademarks of E. I. du Pont de Nemours and Company or its affiliates.

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