Benzovindiflupyr Is Associated with Metabolic Homeostasis Disturbance and Gut–Liver Axis Alterations in Zebrafish: Insights from a Multi-Omics Approach

Benzovindiflupyr (BZF) is a newly developed succinate dehydrogenase inhibitor (SDHI) fungicide that is widely used in crop protection, but its potential effects on non-target aquatic organisms remain a concern. In this study, we exposed adult zebrafish (Danio rerio) to 5.0 and 50 μg/L BZF for 28 days. We investigated its impact on the gut–liver axis using a combination of microbiome, biochemical, histological, and metabolomic analyses. BZF exposure damaged intestinal structure, downregulated barrier-related genes, and altered the composition of the gut microbiota. At the same time, serum lipopolysaccharide (LPS) levels increased, which indicates impaired intestinal barrier integrity and microbial dysbiosis. In the liver, BZF caused histopathological alterations, increased serum ALT, AST, and ALP activities, enhanced oxidative stress, and upregulated inflammation-related genes. Liver metabolomic profiling further showed marked disturbances in redox balance and metabolic homeostasis. Correlation analysis also revealed significant associations between altered microbial taxa and differential liver metabolites. Taken together, these results suggest that BZF exposure disrupted intestinal homeostasis and was associated with hepatic metabolic disturbance in zebrafish, potentially through gut–liver axis perturbation. This study expands current understanding of the toxic effects of SDHI fungicides and provides useful evidence for the ecological risk assessment of BZF in aquatic environments.