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Gut Microbiome and Human Health

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Gut Microbiome and Human Health Presentation 1 Gut Microbiome and Human Health Karen Madsen, PhD University of Alberta Director of Center of Excellence for Gastrointestinal Inflammation and Immunity Research (CEGIIR) Disclosures • Dr. Madsen’s research is funded through the following agencies: – Canadian Institutes for Health Research – Alberta Innovates – Weston Foundation – Digestive Health Strategic Clinical Network – Canadian Association of Gastrointestinal Surgery • Dr. Madsen is a member of the Alberta Digestive Health Strategic Clinical Network; The Canadian Association of Gastroenterology Women’s Advocacy and Action Advisory Board; and the Department of Medicine Research Training Committee The Changing Face of Gut Microbes From enemies….. The Changing Face of Gut Microbes To fellow travellers….. Publications Related to Microbiome Humans have co-evolved with microbes Specific microbial profiles associated with: • Mouth • Respiratory system • Skin • Stomach • Gut • Breast milk The microbiome can be considered a new “organ” The gut microbiota exists as an eco-system within us bacteria, viruses, fungi, archaea….. Tree of life • Over 50 known bacterial phyla • Generally a balance of 6 main phyla found in gut Proteobacteria Bacteroidetes Fusobacteria Firmicutes Disease Health Actinobacteria Verrucomicrobia Species and abundance change over the length of the gut A fine balance of gut microbes Commensals Pathogens • Inhibit pathogen growth • Sepsis, infection • Convert pro-drugs to active • Inflammation metabolites • Liver damage • Degrade polysaccharides of plant origin • Production of carcinogens • Produce folate and Vitamin K • Diarrhea, constipation • Produce short-chain fatty acids • Stimulate and modulate immune function • Regulate body fat storage • Maintain barrier function and stimulate epithelial repair • Stimulate gut motility Individuals differ in the types and quantities of bacteria that colonize the gut … Composition (Relative percentages) Absolute Numbers D Vandeputte et al. Nature 1–5 (2017) doi:10.1038/nature24460 Bacteria are very different genetically from one another and have very different metabolic capacity How do microbes interact with the host? Host-microbial interactions maintain gut homeostasis and can drive pro- and anti- inflammatory immune responses Grigg and Sonnenberg. J of Immunology 198:564. 2017 Altered host-microbial interactions can drive mucosal and systemic disease Grigg and Sonnenberg. J of Immunology 198:564. 2017 DIET AND MICROBIAL METABOLISM Diet, lifestyle, genetics and environmental factors all modulate microbiota DIET Dietary Patterns Specific Foods • Whole grain • Fruits and nuts • Vegetables and legumes Food Constituents • Fiber/carbohydrates • Fat • Protein • Phytochemicals Food-associated commensal microbes What influences the microbiome over life? Gastroenterology, Volume 146, Issue 6, 2014, 1489 - 1499 A large variability is seen in healthy adults in their microbial profiles - Diet is a main determinant of gut microbial composition Voreades et al. Front. Microbiol. Sept 22, 2014 Gut microbial composition can remain relatively stable in healthy adults over time David et al Genome Biology2014 15:R89 But….Perturbations can shift an individual’s microbiome to a new state Subject A Subject B David et al Genome Biology2014 15:R89 Resistance and resilience of the gut microbiota influences health and disease Resistance: Ability to resist perturbations (pathogens, drugs) Resilience: Ability to return to a healthy state following perturbation Sommer et al. Nature Rev Microbiology 2017 Dietary compounds serve as substrates for use by gut microbiota for production of numerous small molecules that influence health and disease Holmes et al. Cell Metabolism 2012;16:559 Plasma metabolites differ significantly between omnivore and vegans Wu et al. Gut 2014;65:63 Trends in Microbiology GUT DYSBIOSIS AND HUMAN DISEASE Low diversity and imbalances in gut microbiota are associated with human disease states Health • High biodiversity and richness • Stable • Primarily Bacteroides and Firmicutes Disease • Low biodiversity • Unstable • Loss of certain groups (SCFA producers) • Increased abundances of Proteobacteria and Fusobacteria Microbiome in Health and Disease • Diseases associated with “imbalances” in gut microbiota – Obesity – Diabetes – Asthma – Allergies – Multiple sclerosis – Inflammatory bowel disease – Rheumatoid arthritis – NEC – Irritable bowel syndrome – Colon and liver cancer – Cardiovascular disease What causes this dysbiosis? Is dysbiosis a cause or a consequence of human disease? Evidence for both! Gevers et al Cell Host Microbe 15:382. 2014 A loss of certain microbial species can remove immune modulating metabolites Huttenhower et al Immunity 2014 40(6):843 Integrated microbial metabolism necessary for health Production of butyrate requires microbial cooperation A loss of SCFA removes many beneficial effects GUT MICROBES AND THEIR METABOLITES CAN ALTER BRAIN FUNCTION AND MOOD Consumption of Fermented Milk Product With Probiotic Modulates Brain Activity Kirsten Tillisch, Jennifer Labus, Lisa Kilpatrick, Zhiguo Jiang, Jean Stains, Bahar Ebrat, Denis Guyonnet, Sophie Legrain–Raspaud, Beatrice Trotin, Bruce Naliboff, Emeran A. Mayer Healthy women • fermented milk product (probiotics) • Non-fermented milk product • Nothing 2x daily for 4 weeks After 4 weeks, women consuming the fermented milk product had altered activity of brain regions that control processing of emotion and sensation Gastroentrology 144:2013 • Randomized, double-blind placebo controlled study of 44 adults with IBS • Took daily B. longum for 6 weeks • Clinical, questionnaires, fMRI, fecal microbiota, urine metabolomics, systemic inflammation • BL reduced depression, but no effect on anxiety or IBS symptoms • Correlated with reduced responses to negative emotional stimuli in multiple brain areas Gastroenterology 2017 GUT MICROBES have a role in colorectal cancer Protection Initiators Modulate response to treatment If gut microbial dysbiosis is a contributing cause to the pathogenesis of disease, then Using therapies aimed at the gut microbiota should help in the prevention or treatment of disease How (and when) to manipulate the gut microbiome? Fiber Fruits, vegetables Prebiotics Probiotics/Antibiotics Defined consortium Fecal microbial transplants HOST DIET AND LUMINAL ENVIRONMENT CAN ALTER RESPONSES TO THERAPY AIMED AT MICROBIAL MODULATION LIMITATIONS AND CAVEATS Microbiome Science Challenges • Association does not equal causation • Are changes in microbial composition biologically relevant? • Could anything else explain the results? – Confounding factors (drugs, diet, age, sex) – Role of diet and specific foods/nutrients emerging area of research • How to overcome technical limitations and challenges – Contamination/batch effects – Low microbial biomass – Bias related to sequencing methodology Hanage WP (2014) Nature 512:247-8; – Cross-sectional vs longitudinal sampling Kim et al. Microbiome 5:52. 2017 CONCLUSIONS Medical Practice in the Future your microbiome will be in your chart • Therapy will be aimed at both the host and the microbiome of the host • Manipulation of an individual’s microbiota with diet, probiotics, prebiotics, or defined bacterial cocktails will be done • Infants will be monitored from birth to ensure colonization with a wide diversity of defined beneficial organisms occurs Acknowledgements Collaborators Madsen Lab • University of Alberta • Dr. Troy Perry – Dr. Karen Kroeker • Dr. Mike Laffin – Dr. Richard Fedorak • Dr. Heekuk Park – Dr. Leo Dieleman • Naomi Hotte – Dr. Bryan Dicken • Robert Fedorak – Dr. Andy Mason • Dr. Ammar Keshteli • Aiden Zalasky • University of Calgary • Braden Millan – Dr. Gil Kaplan • Matt Emberg • George Mason University – Dr. Patrick Gillivet – Dr. Masoumeh Sikaroodi Presentation 2 Diet for Gut Health: The FODMAP Diet and Beyond Associate Professor Jane Muir Disclosures • Board Member/Advisory Panel- - Monash FODMAP Advisory Panel, Nestle Healthcare Nutrition, Meat & Livestock Australia. • Consultant- - George Weston Foods, Meat & Livestock Australia, MGP Ingredients, Nestle Healthcare Nutrition, Sanitarium Health Food Co. • Employee - Monash University, Melbourne, Australia • Research Support- - NHMRC Research Fellowship, NHMRC, ARC linkage, Eva and Les Erdi Foundation, Menzies Foundation, Meat & Livestock Australia. • Other Funding Support- -The department financially benefits from the sales of a digital application and booklets on the low FODMAP diet. Funds raised contribute to research of the Department of Gastroenterology and to the University. A/Prof Muir receives no personal remuneration 2 Diet for Gut Health . What is a healthy gut? . Update in IBS and FODMAP diet therapy. Understanding Gluten and Wheat Avoidance. Diet therapy in the management of Inflammatory Bowel disease. Strategies to change the composition of gut microbiota in IBS. 3 What is a healthy gut? What is optimal gut health for humans? Absorption of Absence of infection, adequate nutrients gut disorders & disease • Irritable bowel syndrome (IBS). Good balance of • Inflammatory bowel gut microbiota disease (IBD) Good laxation and prevention of constipation. What is optimal gut health for humans? Colonic Contents What happens to the gut contents? Gases Short Chain Fatty Acids Water movement CO2, H2, CH4, H2S acetate, butyrate, propionate Selective growth of 75% of certain bacteria faecal PROTEIN matter is CARBOHYDRATE bacteria Toxic by-products of protein Fermentation Bulking & ammonia & phenols laxation effect Important
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