Chronic Triclosan Exposure Promotes Metabolic Dysregulation and Colitis in Mice: A Dose–Dependent Relationship

Triclosan (TCS), a widely used antimicrobial agent in personal care products, typically undergoes phase II metabolism for detoxification. Notably, its phase II metabolites can be reconverted into the parent TCS by microbial activity, revealing their potential toxicological risks. Hence, this study investigated the tissue distribution and metabolic effects in mice following 160 day exposure to TCS at 0.5 or 5 mg/kg/day. The results showed that TCS mainly accumulated in the colon, where it disrupted energy metabolism, enhanced purine metabolism, and elevated reactive oxygen species levels. Lipidomic analyses revealed dose-dependent perturbations: the low dose promoted sphingomyelin synthesis, while the high dose stimulated glycerophospholipid synthesis. Mechanistic evidence from molecular docking and Western blot suggested that these effects might be linked to TCS-induced alterations in mitofusin 2 activity. Overall, these findings provide new insights into the dose-specific mechanisms of TCS-induced intestinal toxicity.