惊鸿 (2025-05-22 19:55):
#paper DOI: 10.1126/science.adp5540 英文标题: A symbiotic filamentous gut fungus ameliorates MASH via a secondary metabolite–CerS6–ceramide axis 时间: 2025年5月1日 北京大学团队在《Science》发表的这项研究,揭示了肠道共生真菌尖镰孢菌(Fusarium foetens)通过分泌代谢物FF-C1靶向抑制宿主CerS6酶,减少毒性脂质C16:0神经酰胺,从而逆转代谢性脂肪肝炎(MASH)的机制。研究通过无菌小鼠模型验证了因果性,并开发了FOCUS-G技术高效分离厌氧真菌,为肠道真菌功能研究提供了新工具。 亮点:① 突破传统“细菌中心”视角,首次建立“真菌-代谢物-宿主”调控轴;② 代谢产物FF-C1结构明确,具备口服药物开发潜力;③ 技术转化路径清晰,真菌组检测或成代谢病早筛新方向。 不足:FF-C1在人体内的代谢稳定性及长期安全性仍需验证,且研究未涉及其他潜在真菌代谢物的协同作用。 总结:该研究为MASH治疗提供了全新靶点,并推动微生物组研究向真菌领域扩展,未来需深化机制探索并加速临床转化。
A symbiotic filamentous gut fungus ameliorates MASH via a secondary metabolite–CerS6–ceramide axis
翻译
Abstract:
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.
翻译
回到顶部