Alleviation of high-lipid diet-induced hepatic steatosis and intestinal injury by berberine in yellow catfish (Pelteobagrus fulvidraco) is associated with modulation of the intestinal microbiota and the FXR pathway.

High-lipid (HL) diets are commonly used in fish farming for their cost-saving and growth-promoting benefits, but often cause hepatic steatosis and intestinal dysfunction. Berberine (BBR), a natural plant alkaloid, exhibits lipid-lowering and health-improving properties, yet its mechanism remains unclear because of its low bioavailability. This study investigated the role of berberine in alleviating HL diet-induced hepatic steatosis and intestinal injury and its mediation by the intestinal microbiota in yellow catfish (Pelteobagrus fulvidraco). The fish were fed a control (8% lipid), HL (12% lipid), or HL diet supplemented with an antibiotic cocktail (HLA) for nine weeks. At week seven, half of the fish in the HL and HLA groups were switched to diets supplemented with 400 mg/kg berberine (named HLB and HLAB, respectively) for two weeks. The HL group exhibited a significantly reduced survival rate and weight gain (P < 0.05), accompanied by severe hepatic steatosis and elevated total cholesterol (TC) content (P < 0.05), as well as intestinal injury. Berberine supplementation (HLB) significantly restored growth performance, reduced hepatic TC and triglyceride (TG) levels, as well as upregulated the expression of intestinal anti-inflammatory cytokines (tgfβ and il10) and suppressed the expression of proinflammatory genes (nfκb, tnfα, and il1β) (P < 0.05). Furthermore, berberine increased intestinal BSH levels and upregulated the hepatic farnesoid X receptor (FXR) signalling pathway, suggesting a potential role of the intestine-liver axis in its metabolic effects. Notably, antibiotic treatment (HLAB) attenuated these beneficial effects, as evidenced by suppressed BSH levels and reduced abundances of potential BSH-producing bacteria (e.g., Escherichia-Shigella and Bacteroides), diminished hepatic FXR signalling, and reversed most of the improvements in morphology and gene expression. Antibiotic treatment alone exerted modest lipid-lowering effects, potentially via direct metabolic interference. Our findings demonstrate that the ameliorative effects of berberine on HL diet-induced hepatic steatosis and intestinal injury are closely associated with microbiota-dependent changes in BSH levels and the activation of the FXR signalling pathway.