Chronic bifenthrin exposure disturbs intestinal homeostasis in common carp via mitochondrial dysfunction, epithelial barrier injury, gut dysbiosis, and metabolic reprogramming.

Bifenthrin is a widely used pyrethroid insecticide that is frequently detected in aquatic environments, yet the mechanisms underlying its chronic intestinal toxicity in fish remain poorly understood. In this study, common carp (Cyprinus carpio) were chronically exposed to bifenthrin at concentrations of 0, 0.1, 1, and 2 μg/L for 30 d, and intestinal toxicity was comprehensively evaluated through biochemical, molecular, histopathological, microbiome, and metabolomic analyses. Bifenthrin exposure significantly altered the activities of digestive enzymes, induced histopathological damage, disrupted oxidative homeostasis, impaired mitochondrial function, and enhanced apoptosis. It also compromised intestinal barrier integrity, with altered tight junction protein expression and increased serum diamine oxidase and D-lactate levels. Furthermore, elevated intestinal and serum lipopolysaccharide levels together with increased pro-inflammatory cytokine levels indicated persistent intestinal inflammation. Moreover, bifenthrin markedly altered the intestinal microbial community, with increased abundance of potential opportunistic bacteria and decreased abundance of several dominant commensal taxa. Metabolomic analysis revealed extensive metabolic reprogramming characterized by disrupted energy metabolism, lipid mediator imbalance, and altered redox-related metabolism, providing insights into the metabolic basis underlying bifenthrin-induced intestinal dysfunction. Integrated microbiome-metabolome correlation analysis further linked gut dysbiosis to metabolic signatures associated with intestinal damage. Collectively, these results demonstrate that chronic bifenthrin exposure causes coordinated disruption of intestinal homeostasis in common carp. This study provides new mechanistic insights into bifenthrin-induced intestinal toxicity and improves our understanding of the chronic toxicological effects of bifenthrin in freshwater fish.