Protective Effects of-Based Mycoprotein against Metabolic Dysfunction-Associated Steatohepatitis via the Gut-Liver Axis.

Abstract

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive subtype of metabolic dysfunction-associated steatotic liver disease, and gut microbiota dysbiosis has been implicated in promoting bacterial translocation and lipopolysaccharide influx into the portal circulation, driving hepatic inflammation. In this study, we evaluated the protective effects of-based mycoprotein against MASH development in two diet-induced murine models. To induce MASH, mice were fed either a high-fat, high-fructose, choline-deficient diet or, for a more severe phenotype, a diet deficient in both choline and methionine. Mice were fed the respective diet for three weeks while receiving oralsupplementation. In both models, supplementation significantly attenuated hepatic steatosis, fibrosis, and inflammation, accompanied by reduced hepatic expression of pro-inflammatory cytokines. In the intestine, tight junction-related genes were upregulated, while pro-inflammatory cytokine gene expression was suppressed. Fecal metabolomics revealed increased cholesterol excretion, indicating reduced cholesterol absorption. Gut microbiota analysis demonstrated a reduction in Proteobacteria and Deferribacterota and an enrichment of Verrucomicrobiota, particularly, in-treated mice. These findings suggest that-based mycoprotein may attenuate MASH progression by improving intestinal barrier function, increasing cholesterol excretion, and reshaping the gut microbial community, collectively contributing to favorable modulation of the gut-liver axis.