Long term chlorantraniliprole exposure induced intestinal and cognitive impairment via inducing lipid and amino acid metabolism dysfunction

Chlorantraniliprole, a widely used anthranilic diamide insecticide, has been linked to adverse effects on mammalian health, yet the precise toxicological mechanisms affecting intestine and brain remain unclear. In this study, mice were exposed to chlorantraniliprole at doses of 80, 160, and 320 mg/kg over a 28-day period. Significant damage to the intestinal barrier was observed, evidenced by decreased expression of tight junction protein ZO-1 and increased levels of inflammatory markers. Cognitive impairments, including decreased locomotor activity, impaired reward response, and increased anhedonia, were observed in behavioral tests. Oxidative stress was overactivated in both colonic and hippocampal tissues. Chlorantraniliprole exposure caused gut dysbiosis, characterized by an increase in Lactobacillus and Allobaculum and a reduction in Parabacteroides. In addition, short-chain fatty acid (SCFA) production decreased following chlorantraniliprole exposure. Metabolomic profiling revealed an increase in lipid-related metabolites and peptides, but a decrease in organic acids and nucleic acids, indicating metabolic dysregulation. Furthermore, iron accumulation and mitochondrial damage were observed in colonic tissue. These findings suggest that chronic chlorantraniliprole exposure disrupts intestinal and neural homeostasis through interconnected pathways involving inflammation, oxidative stress, gut microbiota alterations, and metabolic dysfunction.