Research ArticleMicrobiome

Identifying Gut Microbe–Host Phenotype Relationships Using Combinatorial Communities in Gnotobiotic Mice

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Science Translational Medicine  22 Jan 2014:
Vol. 6, Issue 220, pp. 220ra11
DOI: 10.1126/scitranslmed.3008051

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Mining the Microbiota for Next Generation Probiotics

Our human guts are populated by a mind-boggling number of microbial cells. Identifying members of this vast microbial community that produce specific effects on physiology, metabolism, or immunity is extremely challenging, given the large number of combinations of organisms that could tested. Now, Faith et al. have developed a way to address this challenge. They transplanted intact uncultured microbiota from different human donors into germ-free mice to identify features (phenotypes) of the donor that are transmissible to recipient animals. They then ascertained the ability of the culturable component of a microbiota to transmit these phenotypes. The culture collection was randomly divided into subsets of different sizes, and each subset was introduced into a sterile mouse. By assaying subsets with overlapping bacterial strains, the effect of each strain could be assayed in the context of different community memberships and sizes. Follow-up colonizations with single strains of interest were used to validate those whose presence or absence best explained a phenotype. Screening 94 strain combinations from a single adult’s microbiota revealed strains that modulated the number of regulatory T cells in the colon’s immune system, adiposity, and several facets of metabolism. This approach should facilitate mechanistic studies of how bacterial strains influence health and the discovery of therapeutic probiotics.