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

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-05-01 DOI:10.1126/science.adp5540

Shuang Zhou,Meng Li,Pengcheng Wang,Chenghao Guo,Jinxin Zhang,Xi Luo,Yu-Chen Fan,En-Qiang Chen,Xingshun Qi,Jinjun Chen,Lechi Ye,Hai-Yang Yuan,Wen-Bing Yin,Kai Wang,Ming-Hua Zheng,Yanli Pang,Jie Qiao,Changtao Jiang

引用次数: 0

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.

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一种共生丝状肠道真菌通过次级代谢物- cers6 -神经酰胺轴改善MASH。

众所周知，肠道微生物群与多种人类代谢疾病有关，包括代谢功能障碍相关的脂肪性肝炎（MASH）。真菌越来越被认为是这个群落的重要成员；然而，真菌共生体在代谢性疾病中的作用尚不清楚。我们系统地分离和鉴定了肠道真菌，确定了腐肠镰刀菌是小鼠肠道共生丝状真菌。在小鼠模型中，F. foetens通过肠神经酰胺合成酶6 (CerS6)-神经酰胺轴逆转MASH进展。此外，我们发现FF-C1，一种来自F. foetens的次级代谢物，作为一种CerS6抑制剂，对MASH的进展具有内源性保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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