title: Genetic determinants of in vivo fitness and diet responsiveness in multiple human gut Bacteroides.
abstract: Libraries of tens of thousands of transposon mutants generated from each of four human gut Bacteroides strains, two representing the same species, were introduced simultaneously into gnotobiotic mice together with 11 other wild-type strains to generate a 15-member artificial human gut microbiota. Mice received one of two distinct diets monotonously, or both in different ordered sequences. Quantifying the abundance of mutants in different diet contexts allowed gene-level characterization of fitness determinants, niche, stability, and resilience and yielded a prebiotic (arabinoxylan) that allowed targeted manipulation of the community. The approach described is generalizable and should be useful for defining mechanisms critical for sustaining and/or approaches for deliberately reconfiguring the highly adaptive and durable relationship between the human gut microbiota and host in ways that promote wellness.
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA. Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63108, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Wu
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: McNulty
authors.affiliation: Infectious and Inflammatory Disease Center, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, 92037 CA, USA. A. A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow 127994, Russia.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Rodionov
authors.affiliation: A. A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow 127994, Russia.
authors.forename: Matvei S
authors.initials: MS
authors.lastname: Khoroshkin
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA. Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63108, USA.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Griffin
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA. Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63108, USA.
authors.forename: Jiye
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Monsanto Company, St. Louis, MO 63167, USA.
authors.forename: Phil
authors.initials: P
authors.lastname: Latreille
authors.affiliation: Monsanto Company, St. Louis, MO 63167, USA.
authors.forename: Randall A
authors.initials: RA
authors.lastname: Kerstetter
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique et Aix-Marseille Université 13288 Marseille cedex 9, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Terrapon
authors.affiliation: Architecture et Fonction des Macromolécules Biologiques, Centre National de la Recherche Scientifique et Aix-Marseille Université 13288 Marseille cedex 9, France. Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Bernard
authors.initials: B
authors.lastname: Henrissat
authors.affiliation: Infectious and Inflammatory Disease Center, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, 92037 CA, USA.
authors.forename: Andrei L
authors.initials: AL
authors.lastname: Osterman
authors.affiliation: Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA. jgordon@wustl.edu.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Gordon
mesh_terms: D000818:Animals; D001439:Bacteroides / Q000235:genetics* / Q000378:metabolism*; D004251:DNA Transposable Elements / Q000235:genetics*; D004032:Diet; D041981:Gastrointestinal Tract / Q000382:microbiology*; D015723:Gene Library; D056084:Genetic Fitness / Q000235:genetics*; D056426:Genetic Loci; D005819:Genetic Markers; D005856:Germ-Free Life; D006801:Humans; D051379:Mice; D016254:Mutagenesis, Insertional / Q000379:methods*; D056692:Prebiotics; D017422:Sequence Analysis, DNA / Q000379:methods*; D014990:Xylans / Q000378:metabolism
chemical_list: D004251:DNA Transposable Elements; D005819:Genetic Markers; D056692:Prebiotics; D014990:Xylans; C085118:arabinoxylan