TY - JOUR
T1 - Ulcerative Colitis-associated E. coli pathobionts potentiate colitis in susceptible hosts
AU - Hyungjun Yanga, Hyungjun
AU - Lauridsen, Hengameh Chloé
AU - Struve, Carsten
AU - Allaire, Joannie M
AU - Sivignon, Adeline
AU - Vogl, Wayne
AU - Bosman, Else S.
AU - Ma, Caixia
AU - Fotovati, Abbas
AU - Reid, Gregor S.
AU - Li, Xiaoxia
AU - Petersen, Andreas Munk
AU - Gouin, Sébastien G.
AU - Barnich , Nicolas
AU - Jacobson, Kevan
AU - Yu, Hong Bing
AU - Krogfelt, Karen Angeliki
AU - Vallance, Bruce Andrew
PY - 2020/12/10
Y1 - 2020/12/10
N2 - 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.
AB - 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.
KW - Crohn’s disease
KW - Inflammatory bowel disease
KW - Ulcerative Colitis
KW - in vivo mouse model
KW - intestinal microbiota
U2 - 10.1080/19490976.2020.1847976
DO - 10.1080/19490976.2020.1847976
M3 - Journal article
SN - 1949-0976
VL - 12
JO - Gut Microbes
JF - Gut Microbes
IS - 1
M1 - 1847976
ER -