A symbiotic filamentous gut fungus ameliorates MASH via a secondary metabolite-CerS6-ceramide axis

• 成果类型: Article
• 署名作者: Zhou, Shuang; Li, Meng; Wang, Pengcheng; Guo, Chenghao; Zhang, Jinxin; Luo, Xi; Fan, Yu-Chen; Chen, En-Qiang; Qi, Xingshun; Chen, Jinjun; Ye, Lechi; Yuan, Hai-Yang; Yin, Wen-Bing; Wang, Kai; Zheng, Ming-Hua; Pang, Yanli; Qiao, Jie; Jiang, Changtao
• 署名单位: Peking University; Peking University; Peking University; Shandong University; Sichuan University; Southern Medical University - China; Fudan University; Wenzhou Medical University; Wenzhou Medical University; Chinese Academy of Sciences; Institute of Microbiology, CAS; Peking University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8286
• DOI: 10.1126/science.adp5540
• 发表日期: 2025-05-01
• 关键词: nonalcoholic steatohepatitis; mouse model; nash; metabolites; culture; derivatives; inhibition; mycobiota

摘要

The gut microbiota is known to be associated with a variety of human metabolic diseases, including metabolic dysfunction-associated steatohepatitis (MASH). Fungi are increasingly recognized as important members of this community; however, the role of fungal symbionts in metabolic diseases is unknown. We have systematically isolated and characterized gut fungi, identifying Fusarium foetens as an intestinal symbiotic filamentous fungus in mice. F. foetens reverses MASH progression in mouse models through an intestinal ceramide synthetase 6 (CerS6)-ceramide axis. Moreover, we identified FF-C1, a secondary metabolite from F. foetens, as a CerS6 inhibitor that has an endogenous protective effect on MASH progression.