The Gut Microbiome: 101 Justin Carlson University of Minnesota Where are we now? 360 B.C. 2003 Human Gut Microbes Associated With Obesity Ley et al., Nature. 2006.
Consumer Driven Science For Better of For Worse? (Google Analytics, 2016) Microbiome Trends Relative Frequency: Probiotic Searches Relative Frequency: Microbiome Searches (Google Analytics, 2016)
Probiotic Market $50 B Market Worldwide Exponential Growth in U.S (1998) 34% T.V. Ads Target Gut Health (Google Analytics, 2016) What are the worst assumptions we can make about gut bacteria? There are good and bad bacteria Probiotics always improve health Probiotics help you lose weight All probiotics are safe
Term Definition Probiotics Prebiotics Dietary Fiber live cultures that you eat Example: live bacteria in solution substrate that beneficial bacteria feed on Example: beta-glucans, inulin non-digestible carbohydrates Example: cellulose, hemicellulose Relative Frequency: Microbiome gut microbial Searches genome Gut Microbiome This includes bacteria, metabolites, (Like an organ) substrates, proteins, etc. Gut Microflora bacteria within the distal intestine Example: Bifidobacteria Not all fibers are prebiotics! (Carlson et al., 2016) Fermented Foods vs. Probiotics (Hill et al., Nature Reviews. 2014 )
Bacteria Where Are They? (Appleby, 2008) Taxonomic Classification: 101 Classification Phylum Class Order Family Genus Actinobacteria Actinobacteria Bifidobacteriales Bifidobacteriaceae Relative Bifidobacterium Frequency: Microbiome Searches Species B. breve, B. bifidum, etc. (Nixon, 2007)
Humans: Diverse Hind-Gut Fermenters Relative Frequency: Microbiome Searches (Holmes et al., 2012. Cell Metabolism) Intervention Effect on Microbiota Effect on Metabolism Prebiotics Increase Bifidobacteria and Lactobacillus Increase SCFA production Probiotics Balance microbial diversity Increase SCFA production Fiber Carbohydrates Inversely associated with Bacteroides and Actinobacteria and associated with Firmicutes and Proteobaccteria Negatively associated with Bacteroides and positively associated with Prevotella Increase SCFA production Involved in glycolysis Fats Protein Caloric Restriction Positively associated with Bacteroides and Actinobacteria and negatively associated with Firmicutes and Proteobacteria Positively associated with Bacteroides and negatively associated with Prevotella Relative Frequency: Microbiome Searches Higher percentage of proteobacteria in malnutrition Altered Fatty Acids and Triglycerides Increased BCAA Changes in microbiota which are known to be proinflammatory Iron Depletion Increased Lactobacilli and Enterobacteriaceae and decreased Roseburia spp. and E. rectal group Lower cecal butyrate and propionate GI-Surgery Promote growth of Gammaproteobacteria Altered host-microbial cometabolites and amines Choline-Deficient Diet Gammaproteobacteria higher in cholinedeficient diet Homocysteine increased (Holmes et al., 2012. Cell Metab.)
The Evolution of Symbionts Relative Frequency: Microbiome Searches (Genius, 2009) Are We 10% Human? 100 g of substrate yield 30 g of bacterial biomass Average weight of bacterial biomass production in a lifetime (American Museum of Natural History, Meet Your Microbiome)
How is The Gut Microflora Established? (Yatsunenko et al., Nature. 2014) Establishment of the Microflora 10 Things We Know 1. ~80% if the adult microbiome is established by age 2-3 2. Breast milk is very rich in Lactobacilli and Bifidobacteria 3. C-section formula-fed babies = less diverse microflora 4. Interactions between the microbiota and host immune system start at birth 5. Share about 10% of the microbial genes with the person next to you 6. 5-15% of total diet energy comes from fermentation 7.. Lactobacilli and Bifidobacteria negatively associated with nearly all diseases 8. Changes in the microflora have been correlated with numerous diseases 9. C. dif can be effectively treated with FMT (usually) 10. Average adults carries 3 pounds of bacteria
Antibiotics What Do We Blame? Relative Frequency: Microbiome Searches (Blaser et al., Nature Reviews. 2009) (CDC, 2015)
Four Daily Choices To Promote Gut Health Ten Most Common Probiotics Worldwide Bifidobacterium Lactobacillus B. adolescentis L. acidophilus B. animalis L. casei B. animalis subsp. animalis L. crispatus B. animalis supsp. lactis L. fermentum B. bifidum L. gasseri B. breve L. johnsonii B. infantis L. plantarum B. lactis L. reuteri B. longum L. rhamnosus B. thermophilum L. salivarius (Carlson et al., 2016)
Species Eligible Claims/Purpose Conditions Bifidobacteria adolescentis Bifidobacteria animalis subsp. animalis Bifidobacteria animalis subsp. lactis Bifidobacteria bifidum Bifidobacteria breve Bifidobacteria I nfantis Bifidobacteria longum Lactobacillus acidophilus Lactobacillus casei Lactobacillus fermentum Lactobacillus gasseri Lactobacillus johnsonii Lactobacillus paracasei Lactobacillus plantarum Lactobacillus rhamnosus Lactobacillus salivarius Probiotic that forms/contributes to a natural healthy gut flora Probiotic to benefit health and/or to confer a health benefit Provides live microorganisms that form part of a natural healthy gut flora/that contribute to a natural healthy gut flora/benefit health/confer a health benefit 1.0 x 10^7 to 1.0 x 10^11 CFU of one or more eligible microorganisms/day Lactobacillus Rhamnosus GG Helps to manage acute infectious diarrhea Helps to manage/reduce anti-biotic associated diarrhea 6.0 x 10^9 to 1.2 x 10^10 CFU/day 1.0 x 10^10 to 2.0 x 10^10 CFU/day Lactobacillus johnsonii La1/Lj1/NCC533 Saccharomyces boulardii Saccharomyces cerevisiae An adjunct to physiciansupervised antibiotic therapy in patients with H. pylori infections Helps to reduce the risk of antibiotic-associated diarrhea 1.25 x 10^8 to 3.6 x 10^9 CFU/day 1.0 x 10^10 to 3.0 x 10^10 CFU/day (Carlson et al., 2016) How Do We Analyze The Microflora? (NPR 2014)
FMT: Coming To A Clinic Near You Fecal Microbiota Transplants (FMT)
The Microbiome: Implications For Diabetes Care Rat Models to Clinical Studies Decreased risk for diabetes onset in populations with very high Lactobacillus concentrations. (Germ-free rats) Mucin-producing bacteria may aid in gut strength. Butyrate production may offer decreased risk for TID. (n=8) MGWAS in China (n=345) found mild dysbiosis in T2D patients and decreased amounts of butyrate-producing bacteria (Brown et., 2011; Qin et al., 2012; Brugman et al., 2006)
One Possible Mechanism of Action Lactic Acid Bacteria (Lactobacillus & Bifidobacterium) Lactate Butyrate Producing Bacteria Non-Butyrate Producing Bacteria Butyrate Propionate, Acetate, Etc. Increased mucin synthesis Tighter junctions Decreased Mucin Synthesis Leaky Junctions Increased Gut Integrity Permeable Gut Healthy Individual Autoimmune Individual (Brown et al., ONE. 2011) Current Clinical Studies (Clinicaltrials.gov) Probiotics and Diabetes 17 clinical trials starting or in progress FMT and Diabetes 2 clinical trials enrolling (3/30/16) Prebiotics and Diabetes 4 clinical trials (U.S. and Canada) (Clinicaltrials.gov, 2016)