Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice

Frederic A. Carvalho, Omry Koren, Julia K. Goodrich, Malin E.V. Johansson, Ilke Nalbantoglu, Jesse D. Aitken, Yueju Su, Benoit Chassaing, William A. Walters, Antonio González, Jose C. Clemente, Tyler C. Cullender, Nicolas Barnich, Arlette Darfeuille-Michaud, Matam Vijay-Kumar, Rob Knight, Ruth E. Ley, Andrew T. Gewirtz

Research output: Contribution to journalArticlepeer-review

278 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)139-152
Number of pages14
JournalCell Host and Microbe
Volume12
Issue number2
DOIs
StatePublished - Aug 16 2012

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

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