Identifying gut microbe-host phenotype relationships using combinatorial communities in gnotobiotic mice

Jeremiah J. Faith, Philip P. Ahern, Vanessa K. Ridaura, Jiye Cheng, Jeffrey I. Gordon

Research output: Contribution to journalArticlepeer-review

241 Scopus citations

Abstract

Identifying a scalable, unbiased method for discovering which members of the human gut microbiota influence specific physiologic, metabolic, and immunologic phenotypes remains a challenge. We describe a method in which a clonally arrayed collection of cultured, sequenced bacteria was generated from one of several human fecal microbiota samples found to transmit a particular phenotype to recipient germ-free mice. Ninety-four bacterial consortia of diverse size, randomly drawn from the culture collection, were introduced into germ-free animals. We identified an unanticipated range of bacterial strains that promoted accumulation of colonic regulatory T cells (Tregs) and expansion of Nrp1lo/- peripheral Tregs, as well as strains that modulated mouse adiposity and cecal metabolite concentrations, using feature selection algorithms and follow-up monocolonizations. This combinatorial approach enables a systems-level understanding of microbial contributions to human biology.

Original languageEnglish
Article number220ra11
JournalScience translational medicine
Volume6
Issue number220
DOIs
StatePublished - Jan 22 2014

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