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Héctor Maldonado-Pérez Taylor Sehein Katia Chadaideh The ecosystem inside us ◦ The Microbiome = microbes, their genomes, and the habitat they are found ◦ The gut microbiome: ◦ The most diverse (over 100 trillion bacteria) ◦ Implicated in a range of metabolic processes Influences on Gut Microbial Composition Main Driver: Diet or Genetics? Turnbaugh et al. (2009) Main Driver: Diet or Genetics? Goodrich et al. (2014) Outline • • • • • Part 1: Examining the effects of Diet vs Host Genotype Part 2: Evaluating Responsiveness to Diet Part 3: Assessing Memory associated with Past Diets Evaluation and Critiques Conclusions and Significance Part 1: Diet vs Host Genotype Part 1: Computational Methods • Data generated by 16s rRNA Illumina Sequencing Analyses: •Operational taxonomic unit (OTU) relative abundance •Bray-Curtis dissimilarity-based principal coordinate analysis Part 1: Diet drives gut microbial variance Part 2: Responsiveness to Shifts in Diet Part 2: Computational Methods •Use of OTU relative abundance Analysis: •Microbial Counts Trajectories Infinite Mixture Model Engine (MCTIMME) modeling Part 2: Diet drives reproducible microbial shifts Part 3: Memory Associated with Past Diets • Oscillation of number dependent or stable abundances for OTUs • Determination of “microbial memory” Part 3: Computational Methods • Relative abundance of species-level OTUs Analysis: • Normalization of specific OTU trends per 10k reads in individual mice Part 3: Memory trends in specific OTUs Phylum Bacteroidetes: Phylum Firmicutes: Part 3: Memory trends in specific OTUs Part 3: Memory trends in specific OTUs A Critical Appraisal • No reported conflicts of interest Sources of funding: • the NIH • Brigham and Women’s • General Mills Bell Institute Conclusions and Significance • Dietary factors provide greatest impact on gut microbiome • Reproducible • Past-diet impacts Future directions: • Functional significance of OTUs • Public health implications • Trends in obesity linked to microbiome • Cross-cultural variation Yang, et al (2009) References Carmody, Rachel N., et al. "Diet dominates host genotype in shaping the murine gut microbiota." Cell host & microbe 17.1 (2015): 72-84. Turnbaugh, Peter J., et al. "The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice." Science translational medicine 1.6 (2009): 6ra14-6ra14. Goodrich, Julia K., et al. "Human genetics shape the gut microbiome." Cell. 159.4 (2014): 789-799. Yang, Xing, et al. "More than 9,000,000 unique genes in human gut bacterial community: estimating gene numbers inside a human body." PLoS One 4.6 (2009): e6074.
