The Gut Factor

Thursday November 10, 2016 l 12:00 pm

Probiotics, the gut microbiome

and human health

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.

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

Outline

• Microbiome

• Probiotics in food products and supplements

• Benefits of probiotics in children and adults

• Use of probiotics in clinical practice

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

Roles of gut microbiota

• Nutrients generation and processing; energy homeostasis (metabolic organ)

• Intestinal ontogeny (vascularization, education of the immune system, etc)

• Intestinal barrier function

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, 577–594 http://dx.doi.org/10.1053/j.gastro.2007.11.059

Johansson M, PNAS, 2008

20 µm

Ulcerative colitis

Swidsinski A, J Physiol Pharmacol, 2009

Healthy mouse colon

Localization of gut microbiota

Hooper LV, 2009

Rodriguez JM et al., Microbial Ecology in Health & Disease 2015, 26: 26050 - http://dx.doi.org/10.3402/mehd.v26.26050

Early stages of life (fetal, perinatal, weaning)

are critical for microbiota maturation

Reinhardt, JPGN, 2009

Maternal Diet

Bacteroidetes (Bacteroides spp)

Firmicutes (Streptococcus spp, Clostridium spp)

Proteobacteria (Escherichia coli)

http://dx.doi.org/10.3402/mehd.v26.26050

Rodriguez JM et al., Microbial Ecology in Health & Disease 2015, 26: 26050 - http://dx.doi.org/10.3402/mehd.v26.26050

Early stages of life (fetal, perinatal, weaning) are

critical for microbiota maturation

Reinhardt, JPGN, 2009

Maternal Diet

http://dx.doi.org/10.3402/mehd.v26.26050

Composition of the adult gut microbiota

• Bacteria

• Archaea

• Eukaryotic microorganisms

• Viruses (virome)

Minot, Genome Res, 2011

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Methanobrevibacter Methanosphaera Thermogymnomonas Thermoplasma Nitrososphaera

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44 of 96 samples were positive for Archaea

Gut microbiota dysbiosis is associated to

gastro-intestinal and extra-intestinal diseases

• 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

DYSBIOSIS = qualitative and quantitative changes in the intestinal microbiota, their metabolic activity and their distribution (Holzapfel, Int J Food Microbiol, 1998).

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)

• Term first introduced in 1953 by Kollath

Ilya Ilyich Mechnikov 1845-1916

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.

http://nobelprize.org/nobel_prizes/medicine/laureates/1908/mechnikov-bio.html

Kollath W, Dtsch Zahnarztl Z, 1953, 8(11), 7–16; Hamilton-Miller JM, Br J Nutr, 2003, 90(4):845

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

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

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)

B. bifidum

B. longum L. acidophilus NCFM

https://fbns.ncsu.edu/KlaenhammerLab/Project.html Pictures of bifidobacteria courtesy of Dr Simone Guglielmetti

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 175285, 9 pages, 2008. doi:10.1155/2008/175285

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:10.1038/nrgastro.2014.66

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.

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, antibiotic-associated 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

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

Probiotics for IBS

Bifidobacterium infantis 35624 improves some symptoms of IBS. 1x108 CFU, delivered as a capsule.

Whorwell et al., 2006

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

Probiotics in early life:

a prevention strategy Prevention of:

• Allergic disease

• Colic

• Respiratory and intestinal infections

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.

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)

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, 2014. ISAPP, International Scientific Association for Probiotics and Prebiotics http://isappscience.org/

• Health Canada. The use of probiotic microorganisms in food.

• Guidance Document.

http://www.hc-sc.gc.ca/fn-an/legislation/guide-ld/probiotics_guidance-orientation_probiotiques-eng.php

• 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.

Probiotics claims

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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.

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

http://www.probioticchart.ca/

Probiotics functional foods in Canada

Licensed natural health products database

https://health-products.canada.ca/lnhpd-bdpsnh/index-eng.jsp

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)

Questions?

Making the Most of

Mealtimes in Long-

term Care

November 17, 2016

12:00 – 1:00pm