diet, microbiome and health: past, present and future€¦ · · 2017-05-24available to download...
TRANSCRIPT
December 15, 2016
Presenter:
Cindy D. Davis, Ph.DDirector of Grants and Extramural Activities
Office of Dietary SupplementsNational 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.
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Webinar Series
Diet, Microbiome and Health:Past, Present and Future
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Today’s Faculty
Cindy D. Davis, Ph.D.Director of Grants and Extramural ActivitiesOffice of Dietary SupplementsNational Institutes of Health
Moderator:James M. Rippe, MD – Leading cardiologist, Founder and Director, Rippe Lifestyle Institute
Learning Objectives1. 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?
NUTRI-BITES®
Webinar SeriesDiet, Microbiome and Health: Past, Present and Future
OFFICE OF DIETARY SUPPLEMENTS 7
Diet, Microbiome and Health: Past, Present & Future
Cindy D. [email protected]
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, viral-up 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
What Do Microbes Do For Us?Provide ability to harvest
nutrientsProduce additional
energy otherwise inaccessible to the hostProduce vitaminsMetabolize carcinogensPrevent colonization by
pathogensAssist in the development
of a mature immune system
Development of the Microbiome
Rautava S. et al., Nat. Rev. Gastroenterol. Hepatol. 9:565-576, 2012
Human Intestinal Microbiota over the Lifespan
Kostic et al. Genes and Development 27:701-718, 2013
Dominguez-Bello M.G. et al. Gastronenterology 14): 1713-1719, 2011
NIH Human Microbiome Project (2008-2012)
Phase 1: Survey of the microbiome in humans“Who’s there?”
Is there a “core” microbiome?
Healthy cohort study
Clinically healthy
300 male/female
18-40 y.o.
5 major body regions(18 body sites)
Up to 3 visits in 2 yrs
No antibiotics, probiotics, immunomodulators
Demonstration Projects
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
In healthy American adults, the microbial community composition in each part of the body is unique.
Human Microbiome Project Consortium, Nature 486: 207-214, 2012
PCoA
2 (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 (2013-2016)
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
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
Probiotics
WHO Definition: Live microorganisms that when administered in adequate amounts confer a health benefit on the host
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
Microbial Probiotic Species
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 breadFermented meatSauerkrautWine & beerVinegar
Acidophilus milkSour creamCottage cheese with active cultureMiso (fermented soybean paste)Tempeh (fermented soybean)
Other Fermented Food Sources
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.
Live & Active Cultures
Other Differences MatterDose: 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.
Top Dietary Supplements by U.S. Sales
Top Supplements 2014 (NBJ Supplement Business Report 2015) $Million %Growth
Multivitamins 5,664 0.4
B Vitamins 1,877 5.2
Probiotics 1,365 14.2Calcium 1,150 -2.0
Fish/Animal oils 1,135 -2.8
Vitamin C 1,041 1.0
Vitamin D 707 8.1
Glucosamine/Chondroitin 740 -5.1
Magnesium 680 17.7
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, 2011
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 promisingAs 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/gram4. The supplement is probably better if it has multiple types or strains of bacteria5. 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 effect2. How much of the probiotic people should take3. Who would most likely benefit from taking probiotics
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Bifidobacterium spp(Feces)
Lactobacillus (casei group)(Distal colon contents)
Change in Bacterial Abundance After Consumption of Cocoa-Derived Flavanols
Jang, S. et al., J. Nutr., 2016
Cocoa powder consumption decreased TNF-α and TLR-2, -4 and -9 gene expression in intestinal tissues
David, L.A. et al., Nature, 505: 559-563, 2014
Short- term consumption of diets composed entirely of animal or plant products by 10 subjects:
Alters microbial community structure
Animal-based diet increased bile-tolerant microorganisms and decreased microbes that metabolize plant polysaccharides
Overwhelms inter-individual differences in gene expression
Modifies metabolic pathways
Short-Term Feeding of Plant- and Animal-Based Diets Alters Gut Microbiota
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, 2015
Microbes(Numbers and Types) Dietary Components
Diet and the Microbiome: A Two-Sided Relationship
Bacteria Can Produce New Compounds from Food Components
Food Component Bacterial MetaboliteDietary fiber Butyrate and other SCFAsCholine TrimethylamineSoy isoflavones Equol, O-desmethylangolensinPlant lignans Enterodiol, enterolactoneEllagitannins Urolithins A and BAnthocyanins Hippuric acid & small phenolicsGlucosinolates Isothiocyanates
Dietary Fiber and Cancer
Dietary fiber is associated with decreased risk of colon cancerDietary fibers are fermented by colonic bacteria
to form short chain fatty acidsButyrate is the most widely studied and the
preferred energy source of colonocytesButyrate has differential effects in normal versus
cancer cells
Dietary Fiber and Colon Cancer
Bultman, S.J. Clin. Canc. Res., 20:1-5, 2013
Dietary Fiber and Bacterial Diversity
Martens E. Nature 529:158-159, 2016Sonnenburg, E. et al. Nature 529: 212-215, 2016
Metabolism of Ellagitannins
Cerda et al. J Agric Food Chem 53:227-235, 2005
Oak-Aged Wine
Urolithin Excretion After Intake of Different Ellagic Acid Containing Foods
Food Excretion (%)Strawberry (250 g) 0.06-6.3Raspberry (225 g) 0.21-7.6Red wine (300 ml) 1.8-7.4Walnut (35 g) 1.2-81.0
Cerda et al. J Agric Food Chem 53:227-235, 2005
N=10 volunteers
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 15:408-417, 2015
Obesity Prevalence in the U.S.-2015
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
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 101:15718-23, 2004
Microbiota-Transplantation Studies
ob/ob Diet-induced obesity Humanized MiceDiet-induced obesity
Turnbaugh et al. Cell Host Microbe 3:213-223, 2008Turnbaugh et al. Nature Science Transl Med 1:6-14, 2009
Obesity Alters Gut Bacteria in Different Mouse Models
Ley et al. PNAS 102:11070-5; 2005Turnbaugh et al. Cell Host Microbe 3:213-223, 2008
ob/ob- genetically induced obesity Diet induced obesity
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 444:1022-1023, 2006
Microbiota, Antibiotics and Obesity
Jess T., N.Eng. J. Med. 371: 2526-2527, 2014Cox et al. Cell 158:705-721, 2014
Probiotics Inhibit Obesity in Mice
Yadav et al., J. Biol. Chem. 288:25088-25097, 2014
Fecal Transplants in Humans
Vrieze et al., Gastronenterology 143:913-916, 2012
Autologous- received own feces; allogenic- received feces from lean donor
Fecal Transplants and Obesity
Case ReportA woman underwent a
successful microbial transplant for Clostridum difficileinfectionDeveloped 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
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 163:1079-1094, 2015
A Metagenomic View of our Dinner Plate
Dutton and Turnbaugh, Curr. Opinions Clin. Nutr. and Metabolic Care 15:448-454, 2012
Need to understand both the microbial community and what the microbes are doing
Zoetendal et al. Gut 57:1605-1615, 2008
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.
Questions?
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?
NUTRI-BITES®
Webinar SeriesDiet, Microbiome and Health: Past, Present and Future
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Director
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U.S. Food and Drug Administration
March 2017Day and Time TBD
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Diet, Microbiome and Health: Past, Present and Future