No Guts, No Glory: The Microbiome and Type 2 Diabetes. Meghan Jardine, MS, MBA, RDN, LD, CDE Associate Director of Diabetes Nutrition Education

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1 No Guts, No Glory: The Microbiome and Type 2 Diabetes Meghan Jardine, MS, MBA, RDN, LD, CDE Associate Director of Diabetes Nutrition Education

2 Today s Agenda Describe the microbiota Dysbiosis and diabetes Diet-Microbiota Interactions Application to practice

3 The Microbiota Microbial population living in a specific environment Symbiotic relationship with the host The human microbiome has evolved Mullard A, Nature 2008 May 29;453: Gut Microbiota Worldwatch

4 The Microbiota (cont.) At least 1,000 different known species Weight = 2 to 3 kg 1/3 is common to most humans 2/3 is unique to each individual

5 Microbiota/Microbiome Are we really human? (10 percent human) What about the functionality of our genes? (0.1 to 1% human) We share 99.9% of our genes with other people But we only share 10% of our microbiome Mullard A, Nature 2008 May 29;453: Gut Microbiota Worldwatch

6 Microbiome Microbiome combined genetic make-up Metagenomics - study of the microbiome

7 Microbiome Projects 16S rrna sequencing 3.3 million genes catalogued Human Microbiome Project MetaHit Consortium: Lower gene counts were associated with obesity Human Food Project Mullard A, Nature 2008 May 29;453: Gut Microbiota Worldwatch

8 The Symbiotic Relationship Digest and absorb nutrients Synthesize of vitamins and amino acids Prevent pathogenic colonization Regulate immune function Modulate of GI hormone release Regulate mood and behavior The metabolites released depends on nutrition Kristensen et al. Genome Med. 2016;8:52.

9 What shapes our Microbiota? Natural delivery Breast milk Formula fed babies lack bifidobacteria Stabilized by age of three Changes throughout the lifecycle Mullard A, Nature 2008 May 29;453: Gut Microbiota Worldwatch Moreno-Indias I, et al. Front Microbiol. 2014;5:1-10. Blaser, Martin. Missing Microbes. New York: Henry Holt and Company, LLC Print.

10 Cesarean Delivery Low Risk C-Sections are on the rise Changes strains that inoculate baby s gut Use of prophylactic antibiotics is standard practice Blaser, Martin. Missing Microbes. New York: Henry Holt and Company, LLC Print.

11 Hygiene Our microbiota trains the immune system Healthy tissues might be attacked: Nerves (MS) Intestines (Crohn s disease, Celiac) Pancreas (T1D) Systemic (Rheumatoid arthritis, Lupus) Gut Check: Exploring Your Microbiome (Coursera): Allin, et al. Gut microbiota in patients with type 2 diabetes mellitus.

12 Antibiotic Use 5-day course of antibiotics modifies microbiota Antibiotics and obesity Babies Adults Environmental exposure to antibiotics Gut Check: Exploring Your Microbiome (Coursera): Allin, et al. Gut microbiota in patients with type 2 diabetes mellitus. Moreno-Indias I, et al. Front Microbiol. 2014;5:1-10 Riley, et al. Front Public Health. 2013;1:69

13 Infectious Diseases have Evolved Historical Diseases: Cholera Pneumonia Scarlet fever Diptheria Whooping cough Tuberculosis Smallpox Modern Day Diseases: Obesity Diarrhea Diabetes Atherosclerosis Nonalcoholic fatty liver disease Colitis/Crohn s Disease Autism Asthma Eczema Multiple sclerosis Alzheimer s disease Gut Microbiota Watch:

14 Kingdom Phylum Class Order Family Genus Species Strain Bacteria Firmicutes Clostridia Clostridiales Ruminococcaceae Faecalibacterium F. prausnitzii KLE1255 Cocci Bacilla Spirilla

15 Major Divisions/Phyla Firmicutes (60%) gram positive: largest comprising 200 genera Bacteroidetes (15%) gram negative: 20 genera Actinobacteria (15%) gram positive Proteobacteria (1%) gram negative Esteve E, et al. Curr Opin Clin Nutr Metab Care. 2011;14: Shen J, et al. Mol Aspects Med. 2013;34:39-58 Tilg H, J Clin Invest. 2011;121: Bibiloni R, et al. Ann Nestle Eng. 2009;67:39-47

16 Insulin Resistance/Obesity Profiles Firmicutes:Bacteroidetes Butyrate producing bacteria Bacteria that enhance inflammation Reduced gene diversity Esteve E, et al. Curr Opin Clin Nutr Metab Care. 2011;14: Hartstra, et al. Diabetes Care 2015;38: Tilg H, J Clin Invest. 2011;121: Bibiloni R, et al. Ann Nestle Eng. 2009;67:39-47

17 Endotoxemia and Insulin Resistance High-fat diet elevates plasma lipopolysaccharide (LPS) Reduces gut barrier function LPS gram negative cell walls LPS triggers inflammation Damages beta-cells Inactivates insulin receptors Esteve E, et al. Curr Opin Clin Nutr Metab Care. 2011;14: Shen J, et al. Mol Aspects Med. 2013;34:39-58 Tilg H, J Clin Invest. 2011;121: Bibiloni R, et al. Ann Nestle Eng. 2009;67:39-47

18 Proposed Mechanisms for Insulin Resistance and Obesity DYSBIOSIS HFD gut permeability Monosaccharides and SCFA LPS and insulin resistance Lipogenesis FA oxidation d/t AMPK activity Energy Harvest FA storage Mitochondrial activity Endotoxemia (Insulin Resistance) fatty acid storage in adipocytes

19 Plant-Polysaccharides Fermented by bacteria in colon Short chained fatty acids (SCFA): Butyrate Propionate Acetate Esteve E, et al. Curr Opin Clin Nutr Metab Care. 2011;14: Shen J, et al. Mol Aspects Med. 2013;34:39-58 Tilg H, J Clin Invest. 2011;121(6): Bibiloni R, et al. Ann Nestle Eng. 2009;67:39-47

20 Allin KH, et al. Eur J Endocrinol. 2015;172:R167-R177 Tilg H, et al. Gut. 2014;63: SCFA a Bidirectional Role Energy harvest Stimulates release of gut hormones Improve gut barrier integrity Enhances mitochondrial activity

21 Other Nutrient Induced Changes Protein: BCFA, nitrosamines, phenols, and volatile sulfur compounds Increases abundance of bile-tolerant species Fat: Increases gut permeability Decreases SCFA production Scott et al Pharmacol Res. 2013;69: David et al. Nature. 2014;23:

22 Intestinal Microbiota and CVD Carnitine and choline (red meat, eggs) is metabolized by microbiota Increases plasma trimethyl-amine-oxide (TMAO) Increases CVD Nat Med. 2013;19: N Eng J Med. 2013;368:

23 Impact of Diet on Microbiota De Filippo et al. Compared fecal microbiota of and rural African children (BF) European children (EU) BF diet: cereals (millet, sorghum), legumes (black-eyed peas) and vegetables EU diet: animal protein, sugar, starch, fat, and low in fiber DeFilippo C, et al. PNAS 2010;107:

24 Life in a rural village of Burkina Faso. Carlotta De Filippo et al. PNAS 2010;107: by National Academy of Sciences

25 16S rrna gene surveys reveal a clear separation of two children populations investigated by National Academy of Sciences Carlotta De Filippo et al. PNAS 2010;107:

26 Eating Patterns and Microbiota De Filippis et al. 51 omnivores, 51 vegetarians, 51 vegans all following a Mediterranean Diet Adherence was based on consumption of plantbased foods De Filippis, et al. GUT. 2015;0:1-10.

27 Results Vegan group most adherent to MD Highest fecal SCFA content (p<0.001) species associated with SCFA production and reduced inflammation Urinary TMAO levels lowest for both veg groups (p<0.0001) Omnivore subjects had higher levels of phenolic and indole derivatives

28 What is a Prebiotic? Dietary fiber: 1. Not digested or absorbed in small intestine 2. Fermented by the microbiota 3. Stimulate growth of health-promoting species of: Lactobacilli Bifidobacteria Krumbeck Cur Opin Gastroenterol. 2016;32: Slavin J. Nutrients. 2013;5:

29 Prebiotics 100 g prebiotics produces 30 g bacteria Need 5 to 8 g per day Improve gut barrier integrity Increase SCFA production Enhance the absorption of Ca+, Mg, and Fe+ Slavin J. Nutrients. 2013;5: Cani PD, et al. Current Pharmaceutical Design. 2009;15:

30 Prebiotics Modulate Gut Microbiota: bifidobacteria and lactobacilli BLOOD: LPS levels Inflammation GLP-1 and PYY Ghrelin Satiety Food intake Insulin sensitivity Steatosis/lipogenesis fatty acid oxidation Cani PD, et al. Current Pharmaceutical Design. 2009;15:

31 Prebiotics Breast milk Jerusalem artichoke Chicory root Raw dandelion greens Leeks Onions Garlic Asparagus Whole wheat Beans Bananas Oats Soybeans Psyllium husk (Metamucil ) Jardine MA, OTCE. 2015;35:10-14.

32 Probiotic Definition: Pro = for Bios = life Live micro-organisms Colonize Provide health benefits Bermudez-Brito M, et al. Ann Nutr Metab. 2012;61:

33 Probiotic Benefits Diet Quality Immune function Kills pathogens Probiotics Improves gut barrier function SCFA Reduces ph Kechagia, et al. ISRN Nutr Beena Divya, et al. Eng Life Sci. 2012;12:

34 Probiotics Typical Species Genus Lactobacillus Bifidobacterium Sacharomyces (yeast) Species/Strain L. acidophillus 0 DDS-1 L. casei L. lactis L. rhamnosus L. salviarius B. longum B. infantis B. bifidum S. Boulardii (Brewer s yeast) S. Cervisiae (Baker s yeast) Kumar A, Vandana. Int J Nutr Pharmacol Neurol Dis. 2013;3:

35 Food Sources of Probiotics Plant-Based Sources: Sauerkraut Kimchi Tempeh Soy sauce (namu shoyu) Miso Water kefir Kombucha Dairy-based Sources: Yogurt Kefir Bermudez-Brito M, et al. Ann Nutr Metab. 2012;61: Santosa S, et al. Nutr Rev. 2006;64:

36 Probiotic Supplements Not regulated by the FDA Often not tested Generally are considered safe Look for USP, GMP certifications Take with food 2 hours before or after antibiotics Changes are transient

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38 Probiotics are Effective Treatment Diarrhea IBD IBS Allergies Liver disease Floch, et al. Recommendations for probiotic use. J Clin Gastroenterol. 2015;49:S69-S73.

39 Probiotics for Diabetes Samah, et al. systematic review of 6 RCT: Significant reductions in FBG (p< ) A1C changes inconsistent Anti-inflammatory effects are inconsistent Future directions: Individualize therapies Synbiotics combination of prebiotics and probiotics

40 Fecal Microbiota Transplants (FMT) Clostridium difficile Kills 40,000 people per year Fecal transplants successfully treats 95% (30% with antibiotics) FMT Lean donors obese/metabolic syndrome: Significant in insulin sensitivity gene diversity butyrate producers Vrieze A, et al. Gastroenterology. 2012;142: Hartstra, et al. Diabetes Care 2015;38:

41 Conclusions Diet shapes the composition and activity of the microbiota Focus on high-fiber plant foods: Average American consumes 15 grams fiber/day Increase 14 grams fiber/day reduces energy intake by 10% Ensure servings of prebiotics sources Other considerations: smoking, stress, exercise, sleep, nature, and animals

42 Thank you! Q & A