The Ganoderma atrum Polysaccharide PSG-1 Attenuates Acrylamide-Induced Hepatotoxicity by Modulating the FXR-FGF15-Mediated Gut-Liver Axis

Abstract

Acrylamide (AA), a widespread food-processing contaminant, induces intestinal injury and hepatotoxicity by disrupting barrier function, redox balance, bile acid metabolism, and gut microbial ecology. This study examined the protective benefits of Ganoderma atrum polysaccharide (PSG-1), focusing on the gut-liver axis. PSG-1 reduced serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bile acid (TBA) levels and improved liver histology. It also restored antioxidant defense by enhancing superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities while lowering malondialdehyde (MDA). At the intestinal level, PSG-1 alleviated barrier disruption and reversed gut dysbiosis, restoring Lactobacillus abundance. This microbial modulation coincided with reactivation of the farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF15) pathway, which normalized hepatic cholesterol 7α-hydroxylase (CYP7A1) expression and improved bile acid homeostasis. PSG-1 also corrected retinol metabolism disorders by reducing lecithin-retinol acyltransferase (LRAT) and restoring retinol-binding protein 4 (RBP4). These results demonstrate that PSG-1 protects against AA-induced intestinal and hepatic injury through coordinated regulation of oxidative stress, gut microbiota composition, and FXR-mediated bile acid signaling along the gut-liver axis.