Gut Microbes (2020-11-01)

Ulcerative Colitis-associated E. coli pathobionts potentiate colitis in susceptible hosts

  • Hyungjun Yang,
  • Hengameh Chloé Mirsepasi-Lauridsen,
  • Carsten Struve,
  • Joannie M. Allaire,
  • Adeline Sivignon,
  • Wayne Vogl,
  • Else S. Bosman,
  • Caixia Ma,
  • Abbas Fotovati,
  • Gregor S. Reid,
  • Xiaoxia Li,
  • Andreas Munk Petersen,
  • Sébastien G. Gouin,
  • Nicolas Barnich,
  • Kevan Jacobson,
  • Hong Bing Yu,
  • Karen Angeliki Krogfelt,
  • Bruce A. Vallance

DOI
https://doi.org/10.1080/19490976.2020.1847976
Journal volume & issue
Vol. 12, no. 1

Abstract

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Ulcerative colitis (UC) is a chronic inflammatory condition linked to intestinal microbial dysbiosis, including the expansion of E. coli strains related to extra-intestinal pathogenic E. coli. These “pathobionts” exhibit pathogenic properties, but their potential to promote UC is unclear due to the lack of relevant animal models. Here, we established a mouse model using a representative UC pathobiont strain (p19A), and mice lacking single immunoglobulin and toll-interleukin 1 receptor domain (SIGIRR), a deficiency increasing susceptibility to gut infections. Strain p19A was found to adhere to the cecal mucosa of Sigirr -/- mice, causing modest inflammation. Moreover, it dramatically worsened dextran sodium sulfate-induced colitis. This potentiation was attenuated using a p19A strain lacking α-hemolysin genes, or when we targeted pathobiont adherence using a p19A strain lacking the adhesin FimH, or following treatment with FimH antagonists. Thus, UC pathobionts adhere to the intestinal mucosa, and worsen the course of colitis in susceptible hosts.

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