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

Zhou, Shuang; Li, Meng; Wang, Pengcheng; Guo, Chenghao; Zhang, Jinxin; Luo, Xi; Fan, Yu-Chen; Chen, En-Qiang et al. · Science · 2025

basic_science · Level V

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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 <i>Fusarium foetens</i> as an intestinal symbiotic filamentous fungus in mice. <i>F. foetens</i> reverses MASH progression in mouse models through an intestinal ceramide synthetase 6 (CerS6)-ceramide axis. Moreover, we identified FF-C1, a secondary metabolite from <i>F. foetens</i>, as a CerS6 inhibitor that has an endogenous protective effect on MASH progression.

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