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

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.