Diet and the Human Gut Microbiome: Whose diet is it anyway?

Transcription

1 Soy Nutrition Institute Meeting Minneapolis, MN August 23-24, 2018 Diet and the Human Gut Microbiome: Whose diet is it anyway? Johanna W. Lampe, PhD, RD Public Health Sciences Division Fred Hutchinson Cancer Research Center, and Department of Epidemiology Department of Environmental and Occupational Health Sciences University of Washington 1

2 Outline What is the microbiome? How is it characterized? How does it develop? What affects it? How does it affect responses to diet? How is it associated with health and disease? 2

3 What is the microbiome? The ecological community of commensal, symbiotic, and pathogenic microoganisms that literally share our body space. Joshua Lederberg Lederberg and McCray, The Scientist,

4 The Gut Microbiome: What have we learned? It s complex. ~ 10 trillion microorganisms in the human body species in the human gut Microbiome has 100 times as many genes as the human genome Important symbiosis between human host and microorganisms Sender et al. PLOS Biol 14(8):e ,

5 The Gut Microbiome: Who is there? Bacteria Viruses Protozoa Fungi 5

6 Characterizing the Gut Microbial Community: Who is there and what are they doing? m 16S RNA gene Zoetendal et al., Gut,

7 Bacterial Diversity in the Adult Human Gut Kingdom Phylum Class Order Family Genus Species At least 10 different phyla of bacteria found in the human gut 5 phyla represent majority of bacteria Bacteroidetes and Firmicutes dominate. Bäckhed et al. Science 2004 Marchesi et al, Gut,

8 Comparison of Structural (Taxonomic) and Functional Variation in the Human Gut Microbiome Who is there? What is their functional potential? Relative abundance Human Microbiome Project Consortium. Nature 486:207,

9 How does the microbial community develop? Ottman N et al, Front Cell Infection Microbiol,

10 Fecal Microbiome Relatively Stable in Adults 50 men and women in Multiethnic Cohort, followed for 2 years, sampled every 6 mos. 16S rrna gene sequencing Samples for a person cluster: little variation within a person Fu et al, Cancer Epidemiol Biomarkers Prev, 2018 in press 10

11 Gut Microbial Metabolism Obtain energy and nutrients to live and reproduce Microbiome: >100 times as many genes as human genome Carry out reactions that human gut enzymes cannot: Fermentation Denitrification Sulfate reduction Aromatic fission Hydrolysis/deconjugation Food Human digestion The indigestibles The leftovers Bacterial metabolism 11

12 Fermentation of Carbohydrates: Sugars, Dietary Fiber and Resistant Starch Acetate Propionate Butyrate >81 different glycoside hydrolase families Gill et al, Science, 2006 Tremaroli & Bäckhed, Nature,

13 Microbial Metabolism of Proteins & Amino Acids Proteins Peptides hydrolysis Aromatic Amino acids Other Amino acids Sulfur Amino acids α, β elimination deamination decarboxylation deamination & fermentation Phenols and indoles Ammonia Amines H 2, CO 2, CH 4 NH 3+ /NH 4 Organic acids Sulfur compounds Adapted from Nyangale et al. J Proteome Res,

14 How does diet affect the gut microbiome? Evidence from: Observational studies Globally distinct populations Long-term food pattern consumption Dietary interventions Low- vs high-fiber diets Animal vs plant food sources Macronutrient ratios Reviewed in Arora & Bäckhed. J Int Med 280:339,

15 Global Population Differences: Children in Rural Africa (BF) vs Urban Europe (EU) De Filippo et al PNAS 107:14691,

16 Short-Term Feeding of Plant- and Animal-based Diets Alters Gut Microbiota 10 subjects tracked across 5-d animaland plant-based diets. Baseline Animal Plant Fat, % kcal Protein, % kcal Fiber, g/1000 kcal Animal-based diet increased bile-tolerant microorganisms and decreased microbes that metabolize plant polysaccharides. Bacterial metabolic gene expression (RNA-seq) tends to cluster by diet. Diet doesn t always overcome interindividual differences in GMC structure (16S rrna). 15 David et al, Nature, 505:

17 Multigenerational Effects of Dietary Fiber on Bacterial Diversity Martens E. Nature 529: , 2016 Sonnenburg, E. et al. Nature 529: ,

18 What explains gut microbiome variation within a population? Belgian Flemish Gut Flora Project (n=1106) 69 clinical and questionnaire-based covariates associated with microbiota compositional variation Stool consistency showed largest effect size and medication explained largest total variance. Falony et al. Science 352:560,

19 Gut Microbial Effects on Diet and Human Health Diet Dietary constituents Fuel availability Energy imbalance Disease Risk Cancer CVD Diabetes Gut bacteria 18 19

20 How does the gut microbiome affect diet? Alters exposure to nutrients and bioactives Generates new compounds, that: Serve as energy sources Regulate metabolism Cause or reduce inflammation Cause or reduce oxidative stress Are carcinogenic or chemoprotective 20

21 Bacteria Can Produce New Compounds from Dietary Constituents Food Component Dietary fiber Soy isoflavones Plant Lignans Ellagitannins Anthocyanins Glucosinolates Linoleic Acid Bacterial Metabolites Butyrate and other SCFAs Equol, O-desmethylangolensin Enterodiol, enterolactone Urolithins A and B Hippuric acid & small phenolics Isothiocyanates Conjugated Linoleic Acid 21

22 Microbial Production of Equol and ODMA From Soy Isoflavone Daidzein HO O HO O O Daidzein OH O Dihydrodaidzein OH HO O 80-90% of individuals produce HO OH O OH O-Desmethylangolensin HO OH O Equol OH Cis/Trans-isoflavan-4-ol 20-60% of individuals produce OH 22

23 Urinary Equol Excretion with Soy Challenge nmol/d Equol Excreters Equol Non-excreters 1 Subject 1 equol 60 Lampe et al., PSEBM 217: ,

24 Interidividual differences in ODMA and equol production by gut bacteria in vitro Wide range in capacity of fecal microbes to convert daidzein to ODMA and equol Possemiers et al, FEMS Microbiol Ecol,

25 Obese Adults More Likely to be ODMA-Nonproducer Phenotype 18 to <25 kg/m 2 25 to 29.9 kg/m kg/m 2 P-trend ODMA producers n (%) 142 (59.9) 71 (30.0) 24 (10.1) ODMA nonproducers 29 (48.3) 17 (28.3) 14 (23.3) OR* REF 1.0 (0.5, 2.1) 2.8 (1.2, 6.2) Equol producers n (%) 77 (62.1) 32 (25.8) 15 (12.1) Equol nonproducers 94 (54.3) 56 (32.4) 23 (13.3) OR* REF 1.3 (0.7, 2.2) 1.1 (0.5, 2.2) *n=297; adjusted for age (in years), race, and gender and menopausal status. Frankenfeld et al., Eur J Clin Nutr,

26 Daidzein-Metabolizing Phenotypes and Cardiovascular Risk among 595 Chinese Postmenopausal Women Equol producers, compared to nonproducers, had: Higher fat-free mass Lower systolic and diastolic blood pressure Lower serum triglyceride), hs-crp and FFA O-DMA producers, compared to nonproducers, had: Lower BMI and %body fat Lower total cholesterol Habitual soy isoflavone intake had little relation to CVD risk factors in either metabolizing phenotype. Liu Z-m, PLoS ONE 9(2): e87861,

27 ODMA Producers Have Higher Gut Microbial Diversity Shannon Diversity Index P=0.005 NS Shannon Diversity Index significantly lower in ODMAnonproducing women. No statistically significant difference by equol phenotype. 0 ODMA producers n=115 ODMA nonproducers Equol producers Equol nonproducers Isoflavone-Metabolizing Phenotypes Lampe et al., unpublished 27

28 In a healthy gut microbial community, it is difficult to get new microbes to colonize. 28

29 Microbiome in Health and Disease Eubiosis: Balance Community of commensal, symbiotic, and pathogenic microoganisms in balance. Round and Mazmanian, Nat Rev Immunol,

30 Dysbiosis Aberrant microbiota profiles and/or metabolite alteration characterized by loss of metabolic homeostasis and systemic inflammation. Pathogens Round and Mazmanian, Nat Rev Immunol,

31 Microbiome Dysbiosis and Disease Irritable Bowel Syndrome (IBS) Inflammatory Bowel Disease (IBD) Colon cancer Obesity Diabetes Metabolic syndrome Non-alcoholic fatty liver disease Heart disease Autoimmune disease Asthma Gut-brain axis Sekirov I et al, Physiol Rev,

32 Gut-Brain Axis Regulating satiety and whole body energy balance Regulating brain development Neurologic diseases Autism Depression Dementia Mood Sleep patterns Hepatic encephalopathy 32

33 Soy and Gut Microbiome: What do we know? Differences in the gut microbial activity affect exposure to isoflavone metabolites. Soy supplementation (protein, fiber, isoflavones) alter the gut microbiome in animals and to lesser extent in humans. Huang et al, J Agricultural Food Chem, 64:8695,

34 Where do we go from here in soy and gut microbiome research? Affected by state of microbiome science: Still trying to define a healthy gut microbiome. Large proportion of inter-individual variation in the gut microbiome remains unexplained. Substantial work to be done to establish evidence to support causal relationships and therapeutic potential. Measuring the gut microbiome in soy interventions may help to explain variation in health outcomes if microbial action relates to mechanisms of action. 34

35 QUESTIONS? Everything is dandy and our intestinal biomes are joyous. 35