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。
Science,
2025-5.
DOI: 10.1126/science.adp5540
A symbiotic filamentous gut fungus ameliorates MASH via a secondary metabolite–CerS6–ceramide axis
Abstract:
<br> 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<br> Fusarium foetens</i><br> as an intestinal symbiotic filamentous fungus in mice.<br> F. foetens</i><br> reverses MASH progression in mouse models through an intestinal ceramide synthetase 6 (CerS6)–ceramide axis. Moreover, we identified FF-C1, a secondary metabolite from<br> F. foetens</i><br> , as a CerS6 inhibitor that has an endogenous protective effect on MASH progression.<br>
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