A commonly found gut fungus might provide a new avenue for treating one of the most prevalent chronic liver conditions, according to researchers.
This condition, known as severe metabolic dysfunction-associated fatty liver disease (MAFLD), impacts over one in four adults globally. Previously referred to as nonalcoholic fatty liver disease, it can result in metabolic problems, inflammation, and fibrosis, which is essentially scarring of the liver. When it progresses, it becomes metabolic dysfunction-associated steatohepatitis (MASH).
Despite its widespread occurrence, the FDA has only approved one medication for MASH, and it doesn’t work effectively for everyone. In a recent study, scientists investigated the potential benefits of a fungus called Fusarium foetens.
Changtao Jiang, a prominent professor at Peking University, described the effects of F. foetens as quite remarkable. Jiang co-authored a report detailing this research, which was published on May 1 in the journal Science.
To date, the fungus has only been tested in laboratory settings with human clinical samples and mice. Future studies are set to investigate how it functions in actual human bodies.
Potential Benefits from Fungi
Prior research has indicated that the gut microbiome influences MASH progression, largely because the liver is exposed to byproducts from gut microbes. However, the specific microorganisms and their roles have remained somewhat elusive.
Interestingly, while gut bacteria have been extensively studied, there’s a lack of understanding regarding gut fungi. This gap exists partly due to the complex nutritional needs of gut fungi, which complicates laboratory cultivation, as airborne fungal spores can contaminate samples.
Jiang characterized gut fungi as the “dark matter” of the gut ecosystem. The new research not only examined how F. foetens affects MASH but also identified specific molecules and metabolites involved in this process.
For their study, researchers gathered fecal samples from 100 individuals across five different regions in China and developed a specialized system to cultivate the fungi from these samples in a lab setting. The setup tries to duplicate a real gut environment as closely as possible, using small chips submerged in fecal extract filled with a gelatin-like substance that facilitates nutrient diffusion.
This “clever cultivation” method allowed for the isolation of various fungal species, as noted by Kim Lewis, a biology professor specializing in microbiome therapeutics who was not part of the research.
In addition to analyzing local samples, the team reviewed data from studies in eight other countries, identifying common fungal strains found in guts globally. This broader scope provided insight into diverse diets and environmental interactions that shape the microbiome.
To distinguish true gut fungi from airborne contaminants, the researchers compared fungal communities derived from both air and intestinal samples. They also examined how well the fungal strains could withstand the gut’s temperature and low oxygen levels.
The findings indicated that F. foetens was the most prevalent strain likely to thrive in the gut.
To test the fungus’s impact on fatty liver disease, researchers administered it to mice on a high-fat diet aimed at inducing MASH-like symptoms for two weeks. Although the weight of the treated mice remained comparable to untreated ones, their liver weights were lower, with reduced inflammation and fibrosis signs.
Further analysis revealed that F. foetens treatment lowered the activity of ceramide synthase (CerS), an enzyme involved in producing certain fats. As this enzyme’s activity decreased, so did the associated fat levels. These results were corroborated through additional experiments involving genetically modified mice and those given ceramide supplements.
This research may have significant implications for developing novel clinical therapies targeting gut fungi, Jiang remarked. Lewis echoed this observation, suggesting it opens doors for isolating previously unknown gut microbes that could combat human diseases.
Moving forward, the research team aims to study F. foetens in humans and further investigate the molecular pathways behind its therapeutic effects, as well as the roles of other intestinal fungi in metabolic diseases.
