Prefeeding of berberine alleviates waterborne copper-induced hepatic oxidative stress, lipid deposition, and intestinal microbiota dysbiosis in yellow catfish ( Pelteobagrus fulvidraco)

Copper (Cu) contamination is a common issue in aquaculture and normally leads to hepatic and intestinal damage in fish. Due to the effective lipid-lowering, antioxidative, and intestinal microbiota-maintaining properties of berberine (BBR), it has the potential to be a feed additive to diminish Cu toxicity in fish. This study aimed to determine whether berberine could alleviate hepatic and intestinal damage in yellow catfish (Pelteobagrus fulvidraco) caused by waterborne Cu2+ exposure. The fish with the same weight (2.65 +/- 0.25 g) were assigned to four groups: a control group (Con) that received a control diet for nine weeks; a Cu group, a BBR100 group, and a BBR400 group that received the control diet, 100 mg/kg berberine, and 400 mg/kg berberine for eight weeks, respectively, and after that, they were exposed to 0.8 mg/L Cu2+ for an additional week. The BBR100 and BBR 400 groups had significantly higher weight gain than the Cu group, but significantly lower hepatic and serum total cholesterol and triglyceride levels, and berberine treatment significantly improved intestinal and hepatic histological damage (P < 0.05). Berberine treatment significantly increased intestinal complement 3 and complement 4 levels but distinctly regulated hepatic and intestinal antioxidant enzyme activities while significantly reducing malondialdehyde levels compared to those in the Cu group. In addition, pretreatment with berberine significantly increased the expression levels of intestinal farnesoid X receptor (fxr) and fibroblast growth factor 19, as well as hepatic fxr, and downregulated the expression of its downstream lipogenesis genes (srebp1c, fas, and ppar gamma). Based on 16S rDNA analysis, the abundances of some probiotic bacteria (e.g., Lactobacillus) were elevated, but the abundances of some pathogenic bacteria (e.g., Morganella) decreased in the BBR400 group. At KEGG level 3, the pathway related to "Pathogenic Escherichia coli infection" was significantly enriched in the Cu group but significantly lower enriched in the BBR100 group. These findings indicated that berberine alleviated waterborne copper-induced hepatic and intestinal damage mainly by activating the FXR pathway, reducing oxidative stress and lipid deposition, and maintaining intestinal microbiota homeostasis in yellow catfish.