Identifying gut microbe-host phenotype relationships using combinatorial communities in gnotobiotic mice.
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 (T(regs)) and expansion of Nrp1(lo/-) peripheral T(regs), 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.
Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.
Jeremiah J
JJ
Faith
Philip P
PP
Ahern
Vanessa K
VK
Ridaura
Jiye
J
Cheng
Jeffrey I
JI
Gordon
D050154:Adiposity; D000465:Algorithms; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002432:Cecum / Q000382:microbiology; D005227:Fatty Acids / Q000737:chemistry; D005243:Feces / Q000382:microbiology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D041981:Gastrointestinal Tract / Q000382:microbiology; D005856:Germ-Free Life; D006801:Humans; D007107:Immune System; D039001:Integrin alpha Chains / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D008297:Male; D054892:Metagenome; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000502:physiology*; D039942:Neuropilin-1 / Q000235:genetics; D010641:Phenotype; D049490:Systems Biology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D015703:Antigens, CD; D005227:Fatty Acids; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D039001:Integrin alpha Chains; C091367:alpha E integrins; D039942:Neuropilin-1