A symbiotic filamentous gut fungus ameliorates MASH via a secondary metabolite–CerS6–ceramide axis
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.
Authors
- Jie Qiao (ORCID: https://orcid.org/0000-0003-2126-1376)
- Changtao Jiang (ORCID: https://orcid.org/0000-0002-5206-2372)
- Yu‐Chen Fan (ORCID: https://orcid.org/0000-0002-9126-679X)
- En‐Qiang Chen (ORCID: https://orcid.org/0000-0002-8523-1689)
- Xingshun Qi (ORCID: https://orcid.org/0000-0002-9448-6739)
- Hai‐Yang Yuan
- Ming‐Hua Zheng (ORCID: https://orcid.org/0000-0003-4984-2631)
- Yanli Pang (ORCID: https://orcid.org/0000-0003-1967-2416)
- Meng Li (ORCID: https://orcid.org/0009-0008-3050-8792)
- Lechi Ye (ORCID: https://orcid.org/0000-0003-4818-6900)
- Chenghao Guo (ORCID: https://orcid.org/0009-0009-1174-7955)
- Pengcheng Wang (ORCID: https://orcid.org/0000-0002-3902-6254)
- Wen‐Bing Yin (ORCID: https://orcid.org/0000-0002-9184-3198)
- Xi Luo (ORCID: https://orcid.org/0009-0008-7838-1997)
- Kai Wang (ORCID: https://orcid.org/0000-0001-9705-6366)
- Jinxin Zhang (ORCID: https://orcid.org/0000-0002-6311-4174)
- Jinjun Chen (ORCID: https://orcid.org/0000-0003-4275-9149)
- Shuang Zhou (ORCID: https://orcid.org/0000-0003-2338-7394)
Institutions
- Chinese Academy of Sciences (CN)
- Peking University (CN)
- Sichuan University (CN)
- Fudan University (CN)
- Wenzhou Medical University (CN)
- First Affiliated Hospital of Wenzhou Medical University (CN)
- West China Hospital of Sichuan University (CN)
- Nanfang Hospital (CN)
- Zhongshan Hospital (CN)
- General Hospital of Shenyang Military Region (CN)
- Institute of Microbiology (CN)
- Peking University Third Hospital (CN)
- Advanced Cell Diagnostics (United States) (US)
- Qilu Hospital of Shandong University (CN)
- Southern Medical University (CN)
Publication Details
- Journal
- Science
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1126/science.adp5540
- Citations
- 23
- Primary Topic
- Genomics, phytochemicals, and oxidative stress
- Type
- article
- Field-Weighted Citation Impact
- 18.54