Gut microbiota and genetic polymorphisms correlated with liver fibrosis in metabolic dysfunction-associated steatotic liver disease

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver disorder associated with obesity, type 2 diabetes, and hyperlipidemia. Steatosis leads to fibrosis, cirrhosis, and hepatocellular carcinoma. Gut microbiota and host genetics contribute significantly, while the role of the gut mycobiome is less defined. This study examined gut microbiota, genetic polymorphisms, and fibrosis severity, as well as the association between gut mycobiome and subclinical coronary atherosclerosis (SCA) in MASLD. A total of 156 patients were analyzed for microbial signatures, clinical parameters, and genetic variants (PNPLA3, TM6SF2, HSD17B13). Another 103 patients were evaluated for gut fungi and coronary calcium scores. Advanced fibrosis (F2–F4) was associated with older age, diabetes, elevated AST, PNPLA3 GG genotype, enrichment of Escherichia Shigella and Fusobacterium, and depletion of Lachnospira. Cirrhotic patients with SCA showed increased Candida albicans abundance, suggesting fungal dysbiosis may contribute to cardiovascular risk. These findings showed the interplay between microbiota, genetics, and fungi in MASLD, suggesting potential biomarkers and therapeutic targets.