title: Mining the human gut microbiota for effector strains that shape the immune system.
abstract: The gut microbiota codevelops with the immune system beginning at birth. Mining the microbiota for bacterial strains responsible for shaping the structure and dynamic operations of the innate and adaptive arms of the immune system represents a formidable combinatorial problem but one that needs to be overcome to advance mechanistic understanding of microbial community and immune system coregulation and to develop new diagnostic and therapeutic approaches that promote health. Here, we discuss a scalable, less biased approach for identifying effector strains in complex microbial communities that impact immune function. The approach begins by identifying uncultured human fecal microbiota samples that transmit immune phenotypes to germ-free mice. Clonally arrayed sequenced collections of bacterial strains are constructed from representative donor microbiota. If the collection transmits phenotypes, effector strains are identified by testing randomly generated subsets with overlapping membership in individually housed germ-free animals. Detailed mechanistic studies of effector strain-host interactions can then be performed.
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.
authors.forename: Philip P
authors.initials: PP
authors.lastname: Ahern
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA; Immunology Institute and Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Jeremiah J
authors.initials: JJ
authors.lastname: Faith
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA. Electronic address: jgordon@wustl.edu.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Gordon
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D005243:Feces / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005856:Germ-Free Life / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000276:immunology*; D007113:Immunity, Innate; D051379:Mice; D059013:Microbial Consortia / Q000276:immunology*; D064307:Microbiota / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology