Gut Fungus Potentially Reverses Liver Disease in Mice

Recent groundbreaking research from Peking University has uncovered a promising role for certain gut fungi in combating liver disease. Specifically, a filamentous fungus called Fusarium foetens was found to reverse symptoms of metabolic dysfunction–related steatohepatitis (MASH) in mouse models. This discovery could pave the way for innovative microbiome-based therapies targeting fatty liver disease.

Metabolic dysfunction–associated fatty liver disease (MAFLD) is the most prevalent chronic liver condition globally, affecting roughly 25% of adults. Its spectrum includes severe forms like MASH, which can progress to cirrhosis and liver cancer. Currently, only one medication, a thyroid hormone receptor β-selective agonist, is approved, highlighting the urgent need for new treatments.

While the microbiota's influence on MASH progression is recognized, research has primarily focused on bacterial components. The role of fungi, a diverse part of the gut ecosystem, remains less understood, although they have been linked to conditions such as inflammatory bowel disease and alcoholic liver disease, mainly through pathogenic yeasts like Candida albicans.

In this study, published in Science under the title "A symbiotic filamentous gut fungus ameliorates MASH via a secondary metabolite–CerS6–ceramide axis," scientists explored whether a resident gut fungus could influence liver disease progression. They developed a cultivation system, FOCUS-G, to isolate fungal strains from human fecal samples across China, resulting in over 2,100 cultured fungi.

Using germ-free and specific pathogen–free mice models, researchers assessed colonization, safety, and metabolic effects following oral administration of Fusarium foetens. The fungus successfully colonized the colon without entering the bloodstream or distant tissues, confirmed through genetic and imaging techniques. Whole-genome sequencing showed these strains formed distinct genetic groups, indicating adaptation to the gut environment.

Remarkably, Fusarium foetens treatment reduced liver weight, lowered liver enzymes, and decreased lipid accumulation in mice on a high-fat, choline-deficient diet. Liver histology indicated improvements in fat accumulation, inflammation, and fibrosis, effects that were consistent across different mouse models.

The key mechanism involved a secondary metabolite produced by Fusarium foetens, called FF-C1, which directly binds to ceramide synthase 6 (CerS6). This binding inhibits CerS6 activity, leading to reduced levels of pathogenic ceramides in the liver and plasma. Genetic experiments showed that disrupting CerS6 in intestinal cells nullified the fungus’s beneficial effects, confirming its central role.

Furthermore, administering FF-C1 alone replicated the therapeutic benefits, highlighting its potential as a bioactive compound for treatment. The study suggests that fungi like Fusarium foetens could be harnessed to develop new strategies against fatty liver disease, emphasizing the importance of the gut mycobiome in metabolic regulation.

While promising, further research is needed to explore other beneficial fungal species and their metabolites for potential human therapies. This discovery underscores the complex and beneficial roles that gut fungi can play in maintaining metabolic health.

Source: https://medicalxpress.com/news/2025-05-human-gut-fungus-reverses-liver.html