title: Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice.
abstract: Colitis results from breakdown of homeostasis between intestinal microbiota and the mucosal immune system, with both environmental and genetic influencing factors. Flagellin receptor TLR5-deficient mice (T5KO) display elevated intestinal proinflammatory gene expression and colitis with incomplete penetrance, providing a genetically sensitized system to study the contribution of microbiota to driving colitis. Both colitic and noncolitic T5KO exhibited transiently unstable microbiotas, with lasting differences in colitic T5KO, while their noncolitic siblings stabilized their microbiotas to resemble wild-type mice. Transient high levels of proteobacteria, especially enterobacteria species including E. coli, observed in close proximity to the gut epithelium were a striking feature of colitic microbiota. A Crohn's disease-associated E. coli strain induced chronic colitis in T5KO, which persisted well after the exogenously introduced bacterial species had been eliminated. Thus, an innate immune deficiency can result in unstable gut microbiota associated with low-grade inflammation, and harboring proteobacteria can drive and/or instigate chronic colitis.
authors.affiliation: Center for Inflammation, Immunity, and Infection, Georgia State University, Atlanta, 30303, USA.
authors.forename: Frederic A
authors.initials: FA
authors.lastname: Carvalho
authors.forename: Omry
authors.initials: O
authors.lastname: Koren
authors.forename: Julia K
authors.initials: JK
authors.lastname: Goodrich
authors.forename: Malin E V
authors.initials: ME
authors.lastname: Johansson
authors.forename: Ilke
authors.initials: I
authors.lastname: Nalbantoglu
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Aitken
authors.forename: Yueju
authors.initials: Y
authors.lastname: Su
authors.forename: Benoit
authors.initials: B
authors.lastname: Chassaing
authors.forename: William A
authors.initials: WA
authors.lastname: Walters
authors.forename: Antonio
authors.initials: A
authors.lastname: González
authors.forename: Jose C
authors.initials: JC
authors.lastname: Clemente
authors.forename: Tyler C
authors.initials: TC
authors.lastname: Cullender
authors.forename: Nicolas
authors.initials: N
authors.lastname: Barnich
authors.forename: Arlette
authors.initials: A
authors.lastname: Darfeuille-Michaud
authors.forename: Matam
authors.initials: M
authors.lastname: Vijay-Kumar
authors.forename: Rob
authors.initials: R
authors.lastname: Knight
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Ley
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Gewirtz
mesh_terms: D000818:Animals; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D004755:Enterobacteriaceae / Q000502:physiology; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology / Q000382:microbiology*; D006801:Humans; D008297:Male; D054892:Metagenome; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020560:Proteobacteria / Q000502:physiology*; D051198:Toll-Like Receptor 5 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
chemical_list: D051198:Toll-Like Receptor 5