GUT MYCOBIOME IN THE SPECTRUM OF METABOLIC-DYSFUNCTION ASSOCIATED STEATOTIC LIVER DISEASE (MASLD): FROM MASH TO HEPATOCELLULAR CARCINOMA

Introduction and Objectives

Gut microbiome (GM) dysbiosis is associated with the development and progression of metabolic-dysfunction associated steatotic liver disease (MASLD) and steatohepatitis (MASH). There is still very limited data on the gut mycobiome (GMyco). This study aims to evaluate the composition of the GMyco at different stages of MASLD.

Patients and Methods

28 patients were included: controls (CON), n=6; MASH, n=6; cirrhosis (CIR), n=7; and hepatocellular carcinoma (HCC), n=5. Stool samples were collected and stored in a -80°C freezer for DNA extraction and sequencing (18S region). The single sequence variants (ASVs) obtained were compared to the SILVA database.

Results

77.93% women, average BMI of 31.4 kg/m2, use of antibiotics in the last 6 months (30.4%), and concurrent lipid-lowering drugs in 26.1%. MASH patients had a greater alpha-diversity (p<0,05) than CON. CON had a higher abundance of Ascomycota phylum, and MASH higher Basidiomycota. CON had higher Aspergillaceae family, while there was a higher abundance of Malasseziaceae and Sporidiobolaceae in CIR and Saccharomycetacea in HCC. Only one ASV (genus Naganishia, previously reported as Cryptococcus) was homogeneously distributed in MASLD and absent in CON.

Conclusions

This study shows in an unprecedented way GMyco profile in the different strata of MASLD. Basidiomycetes, higher in MASH, were previously described in obese patients. For the first time, the genus Naganishia was described in this population. Our findings suggest that fungi could be a potential biological marker in the MASLD spectrum in the future.

Conflict of interest: None