Ulcerative Colitis-associated E. coli pathobionts potentiate colitis in susceptible hosts. Issue 1 (9th November 2020)

• Record Type: Journal Article
• Authors: Yang, Hyungjun; Mirsepasi-Lauridsen, Hengameh Chloé; Struve, Carsten; Allaire, Joannie M.; Sivignon, Adeline; Vogl, Wayne; Bosman, Else S.; Ma, Caixia; Fotovati, Abbas; Reid, Gregor S.; Li, Xiaoxia; Petersen, Andreas Munk; Gouin, Sébastien G.; Barnich, Nicolas; Jacobson, Kevan; Yu, Hong Bing; Krogfelt, Karen Angeliki; Vallance, Bruce A.
• Is Part Of: Gut microbes. Volume 12:Issue 1(2020)
• Publication Date: 2020-11-09
• Subjects: Inflammatory bowel disease -- Ulcerative Colitis -- Crohn's disease -- intestinal microbiota -- in vivo mouse model; Gastrointestinal system -- Microbiology -- Periodicals; Microbiology -- Periodicals; Intestine, Small -- Periodicals; 616.3
• DOI: 10.1080/19490976.2020.1847976
• Languages: English
• ISSNs: 1949-0984

Abstract

ABSTRACT: 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.