TSP50 deficiency in neural stem cells aggravates colitis in mice by altering intestinal microbiome

作者：Xiaoli Li, Rong Jin, Zhaoxia Wang, Chunxue Niu, Zhenbo Song, Xiaoling Liu, Jian Huang, Huan Zhang, Xia Qian, Feng Gao, Shuyue Wang, Chunlei Yu, Luguo Sun, Yanxin Huang, Lihua Zheng, Guannan Wang, Ying Sun, Xiaoguang Yang, Yongli Bao, Jiawei Li · 发表于：npj Biofilms and Microbiomes · 年份：2025 · DOI：10.1038/s41522-025-00737-3 · 被引用次数：2 · 研究领域：Gut microbiota and health、Gastrointestinal motility and disorders、Congenital gastrointestinal and neural anomalies

Inflammatory bowel disease (IBD) is a complex disease characterized by persistent chronic inflammation of the gastrointestinal tract and periodic episodes. Despite the increasing number of related studies, the detailed pathogenesis of IBD has not been elucidated. In recent years, host-microbiota interactions in the pathogenesis of IBD have received extensive attention. Testes-specific protease 50 (TSP50) is a potential risk gene for IBD, but whether it can affect the susceptibility of colitis by regulating the gut microbiome is still unclear. Here, we showed that TSP50 deficiency in neural stem cells (NSCs) aggravated colitis in mice by altering intestinal microbiome. Mechanistically, TSP50 maintained the level of neurotransmitter acetylcholine (ACh) by degrading acetylcholinesterase (AChE), thereby maintaining intestinal mucosa and intestinal microecological homeostasis and reducing the susceptibility to colitis. These findings provide a new perspective on the interaction between host and commensal microbiota, which may be beneficial for developing potential therapeutic strategies for IBD.