By

Richard Peet, J.D., Ph.D.

RESEARCHERS HAVE DISCOVERED THAT A COMMON FUNGUS IS PART OF THE GUT MICROBIOTA AND PRODUCES A METABOLITE THAT PROTECTS AGAINST, AND EVEN REVERSES, ADVANCED FORMS OF FATTY LIVER DISEASE IN MICE.1

The scientific name of the fungus is Fusarium foetens. Fatty liver disease is a condition in which excess fat builds up in the liver potentially damaging the organ over time. There are two types of fatty liver disease, nonalcoholic and alcohol associated fatty liver disease.
The most severe form of non-alcoholic fatty liver disease is known as metabolic dysfunction-associated steatohepatitis or MASH. Ceramides are a type of fat molecule that plays a significant role in the development and progression of fatty liver disease including MASH. Whether the fungus F. foetens, or its metabolic products, protect against fatty liver disease in humans is an intriguing possibility.

The microbiota refers to the community of microorganisms that live in a defined environment such as the gut, skin, or moth. These microorganisms include bacteria, archaea, fungi, viruses, and protozoa. The microbiome refers to the entire habitat in which the microorganisms of the microbiota live. The microbiome has been described to include “not only the microorganisms but also their “theatre of activity” – this encompasses microbial structure, metabolites, mobile genetic elements, and the environmental conditions of the habitat.”2 The microbiome includes the genome, or collective DNA of these microbes. Other than bacteria, not much is known about the metabolic activity of these diverse microbes. Pathogenic fungi such as Candida albicans are well known. C. albicans can cause life-threatening infections in cancer and transplant patients. It is therefore exciting to gain insights into what beneficial metabolites fungi might contribute to our health and wellbeing. Can beneficial fungi and their metabolites be harnessed to prevent or treat human disease?” What compounds in our food support the growth of beneficial fungi? Many questions remain unanswered.

To study gut-resident fungi, the researchers developed novel methods to cultivate them under conditions that mimic the human colon. This technological advance enabled the team to discover previously unculturable symbiotic fungal species such as F. foetens. The scientists isolated fungal species from human stool samples collected in different regions of China and identified them by DNA sequencing their genomes. F. foetens was noteworthy for its ability to survive and colonize the mouse gut in low oxygen conditions.

When mice with MASH were treated with F. foetens, the mice exhibited reduced liver weight, lower liver enzyme levels, and less liver fat accumulation, inflammation and fibrosis compared to untreated controls. The researchers discovered that F. foetens secretes a small
molecule, FF-C1, that directly inhibits the enzyme ceramide synthase 6 (CerS6) in the intestine. This inhibition leads to lower levels of C16:0 ceramide, a lipid linked to the progression of liver disease. Administration of isolated metabolite FF-C1 alone could replicate the protective effects, even in the absence of the living fungus. While promising, further research is needed to determine whether similar effects occur in humans and to develop safe, effective treatments derived from this fungal metabolite for human liver disease.

These findings underscore the potential of the fungal microbiome as a rich therapeutic resource, offering new strategies for treating widespread conditions such as fatty liver disease which currently has very limited treatment options. The human genome is estimated to contain about 20,000 to 23,000 protein-coding genes. In contrast, the human microbiome collectively harbors a vastly greater genetic repertoire. Based on analysis of genes found in microbes in the human gut and mouth microbiomes, researchers identified a total of 45, 666,334 unique genes.3 In this study, a unique gene was defined as differing in nucleotide sequence by at least 5% from any other microbial gene. The enormous genetic diversity of the human microbiome equips our bodies with a vast array of metabolic functions. Many of these microbial genes encode enzymes or molecules that humans do not produce, allowing us to digest complex carbohydrates,
synthesize certain vitamins, and metabolize drugs in ways our own genome cannot. The microbiota has a major impact on health. Changes in microbiome gene content have been linked to obesity, diabetes, inflammatory bowel diseases, neurologic conditions, drug metabolism, and immune responses.

While our genome is essential, it is vastly outnumbered and complemented by the genetic potential of our microbiome. The symbiotic relationship between humans and their microbiota has deep implications for understanding health, disease, and the future of personalized medicine. The fungal microbiome likely will be a rich therapeutic resource, offering new strategies for treating disease and improving health and wellness.

  1. Zhou et al., A symbiotic filamentous gut fungus ameliorates MASH via a secondary metabolite – CerS6 –ceramide axis. Science (2025) https://doi.org/10.1126/science.adp5540
  2. Berg et al., Microbiome definition re-visited old concepts and new challenges. Microbiome 8(1): 103 (2020) 103. https://doi.org/10.1186/s40168-020-00875-0
  3. Tierney et al., The landscape of genetic content in the gut and oral human microbiome. Cell Host & Microbe 26: 283-295 (2019). https://doi.org/10.1016/j.chom.2019.07.008