Department of Pediatrics, BC Children's Hospital, University of British Columbia , Vancouver, BC, Canada.
Department of Bacteria, Parasites and Fungi, Statens Serum Institute , Copenhagen, Denmark.
Gut Microbes. 2020 Nov 9;12(1):1847976. doi: 10.1080/19490976.2020.1847976. Epub 2020 Dec 1.
Ulcerative colitis (UC) is a chronic inflammatory condition linked to intestinal microbial dysbiosis, including the expansion of strains related to extra-intestinal pathogenic . 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 -/- 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.
溃疡性结肠炎（UC）是一种与肠道微生物失调相关的慢性炎症性疾病，包括与肠道外致病性相关菌株的扩张。这些“条件致病菌”具有致病性，但由于缺乏相关的动物模型，其促进 UC 的潜力尚不清楚。在这里，我们使用代表性的 UC 条件致病菌（p19A）株建立了一种小鼠模型，以及缺乏单一免疫球蛋白和 Toll-白细胞介素 1 受体域（SIGIRR）的小鼠，这种缺陷会增加对肠道感染的易感性。发现 p19A 株黏附于 -/- 小鼠的盲肠黏膜，引起适度的炎症。此外，它还显著加重了葡聚糖硫酸钠诱导的结肠炎。使用缺乏α-溶血素基因的 p19A 株、使用缺乏黏附素 FimH 的 p19A 株靶向条件致病菌黏附、或在使用 FimH 拮抗剂治疗后，这种增强作用会减弱。因此，UC 条件致病菌黏附在肠道黏膜上，并在易感宿主中加重结肠炎的病程。
