Ring1a protects against colitis through regulating mucosal immune system and colonic microbial ecology

Autor: Yashu Wang, Qianru Li, Jiayu Zhang, Pingping Liu, Huaixin Zheng, Lijuan Chen, Zhen Wang, Chen Tan, Min Zhang, Hongxia Zhang, Wenqing Miao, Yuke Wang, Xiaoyan Xuan, Guoqiang Yi, Peng Wang
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Gut Microbes, Vol 15, Iss 2 (2023)
Druh dokumentu: article
ISSN: 19490976
1949-0984
1949-0976
DOI: 10.1080/19490976.2023.2251646
Popis: ABSTRACTInflammatory bowel disease (IBD) represents a prominent chronic immune-mediated inflammatory disorder, yet its etiology remains poorly comprehended, encompassing intricate interactions between genetics, immunity, and the gut microbiome. This study uncovers a novel colitis-associated risk gene, namely Ring1a, which regulates the mucosal immune response and intestinal microbiota. Ring1a deficiency exacerbates colitis by impairing the immune system. Concomitantly, Ring1a deficiency led to a Prevotella genus-dominated pathogenic microenvironment, which can be horizontally transmitted to co-housed wild type (WT) mice, consequently intensifying dextran sodium sulfate (DSS)-induced colitis. Furthermore, we identified a potential mechanism linking the altered microbiota in Ring1aKO mice to decreased levels of IgA, and we demonstrated that metronidazole administration could ameliorate colitis progression in Ring1aKO mice, likely by reducing the abundance of the Prevotella genus. We also elucidated the immune landscape of DSS colitis and revealed the disruption of intestinal immune homeostasis associated with Ring1a deficiency. Collectively, these findings highlight Ring1a as a prospective candidate risk gene for colitis and suggest metronidazole as a potential therapeutic option for clinically managing Prevotella genus-dominated colitis.
Databáze: Directory of Open Access Journals