Chronic triclosan exposure induce impaired glucose tolerance by altering the gut microbiota

Triclosan (TCS) is an antimicrobial compound incorporated into more than 2000 consumer products. This compound is frequently detected in the human body and causes ubiquitous contamination in the environment, thereby raising concerns about its impact on human health and environmental pollution. Here, we demonstrated that 20 weeks' exposure of TCS drove the development of glucose intolerance by inducing compositional and functional alterations in intestinal microbiota in rats. Fecal-transplantation experiments corroborated the involvement of gut microbiota in TCS-induced glucose-tolerance impairment. 16S rRNA gene-sequencing analysis of cecal contents showed that TCS disrupted the gut microbiota composition in rats and increased the ratio of Firmicutes to Bacteroidetes. Cecal metabolomic analyses detected that TCS altered host metabolic pathways that are linked to host glucose and amino acid metabolism, particularly branched-chain amino acid (BCAA) biosynthesis. BCAA measurement confirmed the increase in serum BCAAs in rats exposed to TCS. Western blot and immunostaining results further confirmed that elevated BCAAs stimulated mTOR, a nutrient-sensing complex, and following IRS-1 serine phosphorylation, resulted in insulin resistance and glucose intolerance. These results suggested that TCS may induce glucose metabolism imbalance by regulating BCAA concentration by remodeling the gut microbiota.