About 25% of adults worldwide have metabolic dysfunction-associated fatty liver disease (MAFLD), a condition that can progress to a more serious form and even liver cancer, yet there are few treatment options. Now, a new study in mice reveals that a compound produced by a gut fungus may help improve liver health.

The findings, published in Science, reveal a new gut-liver pathway and suggest that fungal metabolites may offer a new therapeutic approach for treating MAFLD and related conditions.

Scientists know that gut bacteria can influence the progression of MAFLD, but the role of gut fungi remains unclear. Most studies have focused on yeast such as Candida albicans, but little is known about which fungi can live in the gut and affect liver health, partly because they are hard to grow and study in the lab.

To solve this problem, researchers led by Shuang Zhou at Peking University in Beijing, China, created a new tool called FOCUS-G. This system uses a special device that allows scientists to grow gut fungi directly in their natural environment, making it possible to grow species that couldn’t be grown before.

Gut-adapted fungus

After collecting samples from people across five regions in China and analyzing them with the newly developed tool, the researchers identified more than 2,000 fungal strains representing 161 species. Some fungi, including Candida and Fusarium, were found everywhere, while others were found only in specific locations. 

While Candida albicans and similar fungi can naturally colonize the gut, others, such as Aspergillus and Penicillium, are likely just passing through from the air. Using the new tool, the team identified Fusarium foetens as a gut-adapted fungus that can grow in the low-oxygen, body-temperature conditions of the colon. 

Next, the researchers confirmed the presence of F. foetens in human stool and showed it could successfully colonize the guts of mice without spreading to other tissues or causing harm. A genetic analysis revealed that intestinal strains of F. foetens are different from environmental ones, with unique genes that help them survive in the gut. 

Therapeutic avenue

In mice fed a high-fat diet, those treated with F. foetens showed reduced liver damage, fat buildup, and inflammation compared to untreated mice. These benefits were linked to the fungus’ ability to suppress the production of ceramides—fat-related molecules known to contribute to liver disease. 

Further experiments revealed that F. foetens produces a compound called FF-C1, which inhibits the enzyme CerS6 in the gut. By blocking this enzyme, which is involved in ceramide production, FF-C1 lowered ceramide levels and improved liver health in mice.
The findings suggest that F. foetens may help protect against a more severe form of fatty liver disease that develops from MAFLD and involves liver inflammation and damage, the researchers say. This discovery, they add, “may offer a new therapeutic avenue to treat this highly prevalent disease.”