Abstract

Fluazinam is a widely used agricultural fungicide, but the effects of subchronic exposure remain unclear. This study investigated the liver and intestinal toxicity of fluazinam in mice exposed for 12 weeks at 0.01 and 1 mg/kg bw/day. Results showed that fluazinam caused weight loss, metabolic disorders, and liver toxicity. 16S rRNA sequencing revealed gut microbiota dysbiosis, which is associated with impaired intestinal barrier function and inflammation. Notably, the abundance of bile-acid-metabolizing bacteria (such as Lactobacillus, Lachnospiraceae, and Muribaculum) decreased. Mechanistically, this abnormality triggered a cascade reaction via the gut–liver axis, leading to decreased total bile acid levels, downregulated hepatic synthesis genes (Cyp7a1, Cyp8b1), and upregulated intestinal Fgf15. These changes impaired the farnesoid X receptor pathway and bile acid metabolism, exacerbating liver and intestinal damage. This study revealed that fluazinam mediated metabolic toxicity through the gut–liver axis, providing a novel perspective for its health risk assessment.