Li Xiaoli, Jin Rong, Wang Zhaoxia, Niu Chunxue, Song Zhenbo, Liu Xiaoling, Huang Jian, Zhang Huan, Qian Xia, Gao Feng, Wang Shuyue, Yu Chunlei, Sun Luguo, Huang Yanxin, Zheng Lihua, Wang Guannan, Sun Ying, Yang Xiaoguang, Bao Yongli, Li Jiawei
National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, China.
International Joint Research Center of Stem Cell Bank, Ministry of Science and Technology, Northeast Normal University, Changchun, China.
NPJ Biofilms Microbiomes. 2025 Jun 3;11(1):93. doi: 10.1038/s41522-025-00737-3.
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.
炎症性肠病（IBD）是一种复杂的疾病，其特征为胃肠道持续的慢性炎症和周期性发作。尽管相关研究数量不断增加，但IBD的详细发病机制尚未阐明。近年来，IBD发病机制中的宿主-微生物群相互作用受到了广泛关注。睾丸特异性蛋白酶50（TSP50）是IBD的一个潜在风险基因，但它是否能通过调节肠道微生物群影响结肠炎易感性仍不清楚。在此，我们表明神经干细胞（NSCs）中TSP50的缺乏通过改变肠道微生物群加重了小鼠的结肠炎。机制上，TSP50通过降解乙酰胆碱酯酶（AChE）维持神经递质乙酰胆碱（ACh）的水平，从而维持肠道黏膜和肠道微生态稳态并降低结肠炎易感性。这些发现为宿主与共生微生物群之间的相互作用提供了新的视角，这可能有助于开发IBD的潜在治疗策略。
