Conagra Science Institute. Promoting dietary and related choices affecting wellness by linking evidence-based understanding with practice

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1 NUTRI-BITES Webinar Series Diet, Microbiome and Health: Past, Present and Future will begin at the top of the hour Audio for today s presentation is being broadcast over your computer speakers, so be sure they are turned on and the volume is up Today s presentation in handout form can be downloaded from: (type in your browser) NUTRI-BITES Webinar Series Diet, Microbiome and Health: Past, Present and Future December 15, 2016 Presenter: Cindy D. Davis, Ph.D Director of Grants and Extramural Activities Office of Dietary Supplements National Institutes of Health Moderator: James M. Rippe, MD Leading cardiologist, Founder and Director, Rippe Lifestyle Institute Approved for 1 CPE (Level 2) by the Commission on Dietetic Registration, credentialing agency for the Academy of Nutrition and Dietetics. Conagra Science Institute With a mission of: Promoting dietary and related choices affecting wellness by linking evidence-based understanding with practice 1

2 Webinar logistics CEUs a link to obtain your Continuing Education Credit certificate will be available on this webinar s page at and ed to you within 2 days. A recording of today s webinar and slides as a PDF will be available to download within 2 days at: The presenter will answer questions at the end of this webinar. Please submit questions by using the Chat dialogue box on your computer screen. Today s Faculty Cindy D. Davis, Ph.D. Director of Grants and Extramural Activities Office of Dietary Supplements National Institutes of Health Moderator: James M. Rippe, MD Leading cardiologist, Founder and Director, Rippe Lifestyle Institute Diet, Microbiome and Health: Past, Present and Future NUTRI-BITES Webinar Series Learning Objectives 1. What is the microbiome? 2. What is the evidence that diet can influence the microbiome? 3. How can the microbiome influence the response to dietary components? 4. What is the relationship between diet, the microbiome and disease risk? 2

3 Diet, Microbiome and Health: Past, Present & Future Cindy D. Davis OFFICE OF DIETARY SUPPLEMENTS 7 Outline 1.What is the microbiome? 2.What is the evidence that diet can influence the microbiome? 3.How can the microbiome influence the response to dietary components? 4.What is the relationship between diet, the microbiome and disease risk? The Human Microbiome We are a composite of species: eukaryotic, bacterial, viralup to 10x more microbial cells than human Gut Microbiota= microbes in our GI tract, ~100 trillion organisms Microbiome= their collective genome, >100 times as many genes as human genome 3

4 What Do Microbes Do For Us? Provide ability to harvest nutrients Produce additional energy otherwise inaccessible to the host Produce vitamins Metabolize carcinogens Prevent colonization by pathogens Assist in the development of a mature immune system Development of the Microbiome Rautava S. et al., Nat. Rev. Gastroenterol. Hepatol. 9: , 2012 Human Intestinal Microbiota over the Lifespan Dominguez Bello M.G. et al. Gastronenterology 14): , 2011 Kostic et al. Genes and Development 27: ,

5 NIH Human Microbiome Project ( ) Phase 1: Survey of the microbiome in humans Who s there? Healthy cohort study Is there a core microbiome? Clinically healthy 300 male/female y.o. 5 major body regions (18 body sites) Up to 3 visits in 2 yrs No antibiotics, probiotics, immunomodulators Microbiome associated conditions Skin: eczema, psoriasis, acne GI/oral: esophageal adenocarcinoma, necrotizing enterocolitis, pediatric IBS, ulcerative colitis, Crohn s Disease Urogenital: bacterial vaginosis, circumcision, sexual histories Demonstration Projects In healthy American adults, the microbial community composition in each part of the body is unique. PCoA2 (4.4%) PCoA1 (13%) For each person, est. 1,000 bacterial species and 2,000,000 bacterial genes. Total pool, est. 10,000 species and 8,000,000 genes. However, genetic potential of each microbiome is less variable Human Microbiome Project Consortium, Nature 486: , 2012 Human Microbiome Project ( ) Phase 2: Integrative HMP ihmp what are they doing? Biological properties of both the microbiome and the host microbial composition & multi omics (i.e., transcripts, proteins & metabolites) from microbiome and host longitudinal cohort studies integrated datasets as a community resource Exemplar microbiome associated human conditions: Dynamics of Pregnancy and Preterm Birth: Vaginal & gut microbiomes and host (mother, infant) properties Dynamics of Inflammatory Bowel Disease Onset: GI microbiome and host properties Dynamics of Type 2 Diabetes Onset: GI & nasal microbiomes and host properties 5

6 Dietary Modulation of Gut Microbiota Probiotics: foods or dietary supplements that contain live bacteria Prebiotics: nondigestible food ingredient, which selectively stimulates the growth of gut bacteria Synbiotics: combination of a probiotic with a prebiotic Other factors: tea, cocoa, wine polyphenols, spices 6

7 Probiotics WHO Definition: Live microorganisms that when administered in adequate amounts confer a health benefit on the host Microbial Probiotic Species Probiotics are live microbes that can be formulated into many different products, such as food, drugs, or dietary supplements. Examples: Lactobacillus Bifidobacterium Saccharomyces cerevisiae (yeast) E. coli Bacillus Fermented Foods & Beverages Typically do not contain live cultures due to heat treatment, filtration or food processing to improve shelf life hence, not true probiotics: Sourdough bread Fermented meat Sauerkraut Wine & beer Vinegar 7

8 Other Fermented Food Sources Acidophilus milk Sour cream Cottage cheese with active culture Miso (fermented soybean paste) Tempeh (fermented soybean) Live & Active Cultures Fermented dairy products Some yogurts Some natural cheese Buttermilk Kefir Cultures may or may not be considered probiotic, depending on bacteria levels when eaten & whether bacteria have been shown to confer health benefits. Other Differences Matter Dose: How much are you eating or taking? Companies do not have to indicate the amount on the package. Survival: Is the probiotic dead by the time you eat it? The product may have contained a suitable number of live bacteria when manufactured but the consumer doesn t know if it is available at the end of the product s shelf life. 8

9 Top Dietary Supplements by U.S. Sales Top Supplements 2014 (NBJ Supplement Business Report 2015) $Million %Growth Multivitamins 5, B Vitamins 1, Probiotics 1, Calcium 1, Fish/Animal oils 1, Vitamin C 1, Vitamin D Glucosamine/Chondroitin Magnesium Mechanisms of Probiotic Action O Toole and Cooney, Interdisciplinary Persp. Infect. Diseases 2008 Continuous Probiotic Exposure Increases Longevity in Mice 10 month female ICR mice fed a chow diet and gavaged with Bifidobacterium animalis subsp. lactis LKM512 or vehicle daily for 11 months Matsumoto et al. PloS One 6:e23652,

10 Proposed Health Effects of Probiotics Conclusions Probiotics to Improve Health Effects are strain specific Intervention descriptions are lacking Safety is underreported and understudied Evidence for efficacy is inconclusive, but promising As any proof of causality requires clinical intervention studies in humans in different populations, rigorous and detailed documentation will enhance reproducibility and circumvent confusion Science of probiotics is still in its infancy Probiotics Practice Applications What we know: 1. There s preliminary evidence that some probiotics are helpful preventing diarrhea caused by infections and antibiotics, improving symptoms of irritable bowel syndrome 2. The U.S. Food and Drug Administration has not approved any probiotics for preventing or treating any health problem 3. Probiotic supplements should contain at least 1 billion live cells/gram 4. The supplement is probably better if it has multiple types or strains of bacteria 5. If people are generally healthy, probiotics have a good safety record. However, there have been reports linking probiotics to severe health effects, such as dangerous infections, in people with weakened immune systems What we don t know: 1. Which probiotics are helpful and which are not not all probiotics have the same effect 2. How much of the probiotic people should take 3. Who would most likely benefit from taking probiotics 10

11 Change in Bacterial Abundance After Consumption of Cocoa Derived Flavanols Bifidobacterium spp (Feces) Lactobacillus (casei group) (Distal colon contents) Copies per gram (cpg) 1.6e+6 1.4e+6 1.2e+6 1.0e+6 8.0e+5 6.0e+5 4.0e+5 Copies per gram (cpg) 4e+8 * * 3e+8 2e+8 1e+8 2.0e Cocoa powder consumption decreased TNF α and TLR 2, 4 and 9 gene expression in intestinal tissues Jang, S. et al., J. Nutr., 2016 Short Term Feeding of Plant and Animal Based Diets Alters Gut Microbiota Short term consumption of diets composed entirely of animal or plant products by 10 subjects: Alters microbial community structure Animal based diet increased biletolerant microorganisms and decreased microbes that metabolize plant polysaccharides Overwhelms inter individual differences in gene expression Modifies metabolic pathways David, L.A. et al., Nature, 505: , 2014 Diet Dominates Host Genotype in Shaping the Mouse Gut Microbiota 5 Inbred and >200 outbred mouse strains were fed a low fat, high plant polysaccharide diet (LFPP:22.2%KCAL protein, 16% fat, 61% CHO) and a high fat, high sugar diet (HFHS: 14.8% KCAL protein, 40.6% CHO, 44.6% fat) Carmody et al., Cell Host & Microbe 17:72 84,

12 Diet and the Microbiome: A Two Sided Relationship Microbes (Numbers and Types) Dietary Components Bacteria Can Produce New Compounds from Food Components Food Component Bacterial Metabolite Dietary fiber Butyrate and other SCFAs Choline Trimethylamine Soy isoflavones Equol, O desmethylangolensin Plant lignans Enterodiol, enterolactone Ellagitannins Urolithins A and B Anthocyanins Hippuric acid & small phenolics Glucosinolates Isothiocyanates Dietary Fiber and Cancer Dietary fiber is associated with decreased risk of colon cancer Dietary fibers are fermented by colonic bacteria to form short chain fatty acids Butyrate is the most widely studied and the preferred energy source of colonocytes Butyrate has differential effects in normal versus cancer cells 12

13 Dietary Fiber and Colon Cancer Bultman, S.J. Clin. Canc. Res., 20:1-5, 2013 Dietary Fiber and Bacterial Diversity Martens E. Nature 529: , 2016 Sonnenburg, E. et al. Nature 529: , 2016 Metabolism of Ellagitannins Oak-Aged Wine Cerda et al. J Agric Food Chem 53: ,

14 Urolithin Excretion After Intake of Different Ellagic Acid Containing Foods Food Excretion (%) Strawberry (250 g) Raspberry (225 g) Red wine (300 ml) Walnut (35 g) N=10 volunteers Cerda et al. J Agric Food Chem 53: , 2005 Diet, Microbial Metabolism and Cardiovascular Disease Hazen, S.L. Curr. Opin. Lipidol. 25: 48-53, 2014 Dietary Allicin Reduces Metabolism of L Carnitine to TMAO Wu et al. J. Functional Foods 15: ,

15 Obesity Prevalence in the U.S Content source: National Center for Chronic Disease Prevention and Health Promotion More is Not Always Better. Energy Intakes and Expenditures Are Linked to Chronic Disease! Some Eat More and Grow More Than Others 15

16 Germ Free Mice Eat More and Grow Less Conventionalized mice (CONV-D)=formerly germ free (GF) recipients of a gut microbiota transplant from conventionally raised (CONV-R) donors Bakhed et al. PNAS 101: , 2004 ob/ob Microbiota Transplantation Studies Diet-induced obesity Humanized Mice Diet-induced obesity Turnbaugh et al. Cell Host Microbe 3: , 2008 Turnbaugh et al. Nature Science Transl Med 1:6 14, 2009 Obesity Alters Gut Bacteria in Different Mouse Models ob/ob- genetically induced obesity Diet induced obesity Ley et al. PNAS 102: ; 2005 Turnbaugh et al. Cell Host Microbe 3: ,

17 Human Gut Microbes and Obesity 12 Unrelated obese subjects on fat or carbohydrate restricted diet Monitored for one year Increase in Bacteroidetes correlates with change in weight Ley et al. PNAS 444: , 2006 Microbiota, Antibiotics and Obesity Jess T., N.Eng. J. Med. 371: , 2014 Cox et al. Cell 158: , 2014 Probiotics Inhibit Obesity in Mice Yadav et al., J. Biol. Chem. 288: ,

18 Fecal Transplants in Humans Autologous received own feces; allogenic received feces from lean donor Vrieze et al., Gastronenterology 143: , 2012 Fecal Transplants and Obesity Case Report A woman underwent a successful microbial transplant for Clostridum difficile infection Developed new onset obesity after receiving stool from an overweight donor Alang and Kelly, Open Forum Infec. Dis. 2:ofv004, 2015 Microbes (Numbers and Types) Food Components and Energy Microbial Metabolite(s) Disease Risk 18

19 Can Your Microbiome Tell You What to Eat? High interpersonal variability in post meal glucose observed in an 800 person cohort Using personal and microbiome features enables accurate glucose response prediction Prediction is accurate and superior to common practice in an independent cohort Short term personalized dietary interventions successfully lower post meal glucose Zeevi D., et al. Cell 163: , 2015 A Metagenomic View of our Dinner Plate Dutton and Turnbaugh, Curr. Opinions Clin. Nutr. and Metabolic Care 15: , 2012 Need to understand both the microbial community and what the microbes are doing Zoetendal et al. Gut 57: ,

20 Practice Applications 1. Microbiome research is an emerging area of science and there are many research opportunities available. 2. The microbiome is integral to human physiology, maintenance of health and development of disease. 3. There is a two sided relationship between diet and the microbiome. 4. Dietitians need to actively stay informed about advances in this field. Cindy D. Davis davisci@mail.nih.gov 20

21 Questions? Diet, Microbiome and Health: Past, Present and Future NUTRI-BITES Webinar Series Based on this webinar the participant should be able to: 1. What is the microbiome? 2. What is the evidence that diet can influence the microbiome? 3. How can the microbiome influence the response to dietary components? 4. What is the relationship between diet, the microbiome and disease risk? Conagra Science Institute Nutri-Bites Webinar details A link to obtain your Continuing Education Credit certificate will be will be available on our website and ed within 2 days Today s webinar will be available to download within 2 days at: For CPE information: acontinelli@rippelifestyle.com Recent CEU webinars archived at the Conagra Science Institute website: Using Technology to Enhance Your Weight Loss Practice Exploring the Benefits of Increased Protein Consumption: To Improve Health Outcomes Eating Frequency and Weight Management 21

22 Next Conagra Science Institute Nutri-Bites Webinar An Update from FDA on the Revised Nutrition Facts Panel, Coming Soon Douglas Balentine, PhD Director Office of Nutrition and Food Labeling U.S. Food and Drug Administration March 2017 Day and Time TBD How are we doing? Stay on the line for a brief survey about today s Conagra Science Institute Nutri-Bites webinar: Diet, Microbiome and Health: Past, Present and Future Thank you! 22