The Gut Factor. Probiotics, the gut microbiome and human health. Thursday November 10, 2016 l 12:00 pm

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1 The Gut Factor Probiotics, the gut microbiome and human health Thursday November 10, 2016 l 12:00 pm

2 Dr. Elena Comelli is an Assistant Professor and holds the Lawson Family Chair in Microbiome Nutrition Research at the Department of Nutritional Sciences and the Centre for Child Nutrition and Health at the University of Toronto. Since 2015, Dr Comelli is also Adjunct Professor at the Department of Kinesiology at Brock University. Elena s group investigates how dietary interventions (including probiotics and vitamin D) in early life can impact health and disease later in life via the gut microbiota, particularly inflammatory conditions. Recently her group and collaborators have proposed the existence of a gut microbiota-bone axis, which she is studying in the context of the metabolic syndrome. Another focus is on probiotics and gut microbiota regulation of host gene expression including at the post-transcriptional level via microrna.

3 The Gut Factor: Probiotics, the Gut Microbiome, and Human Health Elena M. Comelli, PhD Assistant Professor and Lawson Family Chair in Microbiome Nutrition Research Department of Nutritional Sciences and Centre for Child Nutrition and Health, University of Toronto, Canada

4 Outline Microbiome Probiotics in food products and supplements Benefits of probiotics in children and adults Use of probiotics in clinical practice

5 Microbiota and Microbiome MICROBIOTA: The assemblage of microorganisms present in a defined environment. METAGENOME: The collection of genomes and genes from the members of a microbiota. MICROBIOME: refers to the entire habitat, including the microorganisms, their genomes, and the surrounding environmental conditions (biome: the biotic and abiotic factors of given environments). Marchesi and Ravel, Microbiome, 2015

6 Roles of gut microbiota Nutrients generation and processing; energy homeostasis (metabolic organ) Intestinal ontogeny (vascularization, education of the immune system, etc) Intestinal barrier function

7 Composition and luminal concentrations of dominant microbial species in various regions of the gastrointestinal tract R. Balfour Sartor Microbial Influences in Inflammatory Bowel Diseases Gastroenterology, Volume 134, Issue 2, 2008,

8 Localization of gut microbiota Healthy mouse colon 20 µm Johansson M, PNAS, 2008 Ulcerative colitis Hooper LV, 2009 Swidsinski A, J Physiol Pharmacol, 2009

9 Early stages of life (fetal, perinatal, weaning) are critical for microbiota maturation Maternal Diet Firmicutes (Streptococcus spp, Clostridium spp) Proteobacteria (Escherichia coli) Bacteroidetes (Bacteroides spp) Rodriguez JM et al., Microbial Ecology in Health & Disease 2015, 26: Reinhardt, JPGN, 2009

10 Early stages of life (fetal, perinatal, weaning) are critical for microbiota maturation Maternal Diet Rodriguez JM et al., Microbial Ecology in Health & Disease 2015, 26: Reinhardt, JPGN, 2009

11 Amplicon yield Backhed, Cell Host & Microbes, 2012 Composition of the adult gut microbiota Bacteria Archaea Eukaryotic microorganisms Viruses (virome) BACTERIA VIROME ARCHAEA (up to 10% of total microorganisms) Archaea Minot, Genome Res, 2011 Bacteria Methanobrevibacter Methanosphaera Thermogymnomonas Thermoplasma Nitrososphaera 44 of 96 samples were positive for Archaea 4H 2 + CO 2 CH 4 + 2H 2 O + energy Hoffmann, PLoS ONE, 2013

12 Gut microbiota dysbiosis is associated to gastro-intestinal and extra-intestinal diseases DYSBIOSIS = qualitative and quantitative changes in the intestinal microbiota, their metabolic activity and their distribution (Holzapfel, Int J Food Microbiol, 1998). Crohn s disease: Manichanh, 2006; Sokol, 2009 Ulcerative colitis: Sokol, 2008; Swidsinski, 2009 Pouchitis: Kuhbacher, 2006; Lim, 2009 Irritable bowel syndrome: Malinen, 2005 Coeliac disease: Sanz, 2007; Collado, 2009 Colo-rectal cancer: Sobhani, 2011 Diabetes types I and II: Brugman, 2006; Cani and Delzenne, 2009 HIV: Gori, 2008 Autism: Finegold, 2002 Obesity: Ley, 2006; Kalliomaki, 2008; Zhang, 2009 Non-alcoholic fatty liver disease: Mouzaki, 2013 Anorexia: Armougom, 2009 Allergy: Kirjavainen, 2002 Rheumatoid arthritis: Vaahtovuo, 2008

13 Probiotics definition Live microorganisms which when administered in adequate amounts confer a health benefit on the host (FAO/WHO, 2001) Recently revised: Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (Hill C et al., Nat. Rev. Gastroenterol. Hepatol., 2014)

14 He took up the study of the flora of the human intestine and developed a theory that senility is due to poisoning of the body by the products of certain of these bacteria. To prevent the multiplication of these organisms he proposed a diet containing milk fermented by bacilli which produce large amounts of lactic acid and for a time this diet became widely popular. Ilya Ilyich Mechnikov bio.html Term first introduced in 1953 by Kollath Kollath W, Dtsch Zahnarztl Z, 1953, 8(11), 7 16; Hamilton-Miller JM, Br J Nutr, 2003, 90(4):845

15 What are probiotics WHO guidelines Alive microorganisms. Dead bacteria (paraprobiotics; Taverniti, 2011) and bacterial products (postbiotics; Tsilingiri, 2013) do not fall under the probiotics definition. Identification and classification of the organism (genus, species, strain; deposited at culture collection) Suitable and shelf-stable formulation Evidence of efficacy in randomized clinical trials Safety assessment

16 What probiotics are not Live vaccine Not equal to native putatively beneficial microorganisms Live active cultures (these are microbes associated with food usually employed for fermentation) Fecal Microbial Transplantation (FMT) mixtures (undefined, from donors) Sanders ME, Functional Foods Reviews, 2009; Hill C, Nat Rev Gastroenterol Hepatol, 2014

17 Most commonly used probiotic microorganisms Lactobacilli (L. plantarum; L. acidophilus NCFM; L. johnsonii La1) Bifidobacteria (B. animalis; B. longum; B. bifidum) Lactococci Bacillus species (B. clausii) Escherichia species (E. coli Nissle 1917) Enterococcus species Yeasts (S. boulardii) L. acidophilus NCFM B. longum B. bifidum Pictures of bifidobacteria courtesy of Dr Simone Guglielmetti

18 Mechanisms of action of probiotics Paul W. O'Toole and Jakki C. Cooney, Probiotic Bacteria Influence the Composition and Function of the Intestinal Microbiota, Interdisciplinary Perspectives on Infectious Diseases, vol. 2008, Article ID , 9 pages, doi: /2008/175285

19 Possible distribution of mechanisms among probiotics Hill, C. et al. (2014) The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic Nat. Rev. Gastroenterol. Hepatol. doi: /nrgastro

20 Guidelines for the evaluation of probiotics for food use Report of a Joint FAO/WHO Working Group on Drafting Guidelines for the Evaluation of Probiotics in Food. London, ON, Canada, 2002.

21 Substantiated probiotics effects Recommendations can be made for: Prevention of upper respiratory tract infections Prevention of pouchitis Prevention and management of necrotizing enterocolitis, bacterial vaginosis, antibioticassociated diarrhea (including C. difficile infection) Treatment of atopic eczema in cow milk allergy Treatment of infectious diarrhea Taibi and Comelli, Appl Physiol Nutr Metab, 2014

22 Additional substantiated probiotic effects Prevention of hypercholesterolemia Management of constipation Reduction of recurrent urinary tract infections Improvement of irritable bowel syndrome (IBS) symptoms Reduction of antibiotics side effects in H. pylori eradication Reduction of infantile colics (no consensus) Taibi and Comelli, Appl Physiol Nutr Metab, 2014

23 Probiotics for IBS Bifidobacterium infantis improves some symptoms of IBS. 1x10 8 CFU, delivered as a capsule.

24 Whorwell et al., 2006

25 Additional benefits being evaluated Metabolic syndrome Inflammatory Bowel Disease (IBD) Oral health Anxiety Reid G. et al., J. Clin. Gastroenterol., 2003 Taibi and Comelli, Appl Physiol Nutr Metab, 2014

26 Probiotics in early life: a prevention strategy Prevention of: Allergic disease Colic Respiratory and intestinal infections selected probiotics may be used within a prophylactic protocol may be helpful for children in day care centers (increased risk of developing common infectious diseases compared to children staying at home) Villa and Comelli, 2015, Implications for Probiotic Use in Healthy Children. In: Probiotics in children. Nova Publisher, New York Lu N et al., 2004, Child Care Health Dev.

27 Are these core benefits of probiotics or rather strain specific? Proposed core benefits: - Supporting a healthy gut microbiota - Supporting a healthy digestive tract Experts Panel convened by ISAPP in 2013; published in Hill C et al, Nat Rev Gastroenterol Hepatol, ISAPP, International Scientific Association for Probiotics and Prebiotics

28 Health Canada. The use of probiotic microorganisms in food. Guidance Document.

29 Probiotics claims Strain-specific claims: claims about health benefits or effects of specific strains. At the present time there are no strain-specific claims accepted by Health Canada. Non-strain-specific claims: statements about the nature of probiotics. A closed list of such claims has been prepared by Health Canada.

30 Health Canada Guidance Document, The word "gut" may be replaced by the expression "digestive tract" in these claims.

31 Labelling guidelines Latin name of the microorganism (genus and species) with strain identity Amount of probiotic(s) contained in the product at the end of its shelf life expressed in colony forming units per serving of stated size of the food The probiotic must be identified in the ingredients list by its common name or by a class name such as bacterial culture. If bacterial culture is used, the identity of the probiotic(s) should be given next to the claim Health Canada Guidance Document, 2009.

32 Probiotic products in Canada (indications for adults, pediatric and vaginal health)

33 Probiotics functional foods in Canada

34 Licensed natural health products database

35 Conclusions Probiotics sustain the gut microbiota and provide an approach to disease prevention and management Some benefits are common across various probiotics and some are specific Strains with substantiated effects are available in Canada (foods or supplements)

36 Questions?

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