Long-Term Triclocarban Exposure Induced Enterotoxicity by Triggering Intestinal AhR-Mediated Inflammation and Disrupting Microbial Community in Mice

作者：Yuchen Song, Hehua Lei, Zheng Cao, Cui Zhang, Chuan Chen, Mengjing Wu, Huabao Zhang, Ruichen Du, Liu Lijun, Xiaoyu Chen, Limin Zhang · 发表于：Chemical Research in Toxicology · 年份：2024 · DOI：10.1021/acs.chemrestox.4c00042 · 被引用次数：8 · 研究领域：Immune cells in cancer、Immune Response and Inflammation、Gut microbiota and health

Exposure to triclocarban (TCC), a commonly used antibacterial agent, has been shown to induce significant intestine injuries and colonic inflammation in mice. However, the detailed mechanisms by which TCC exposure triggered enterotoxicity remain largely unclear. Herein, intestinal toxicity effects of long-term and chronic TCC exposure were investigated using a combination of histopathological assessments, metagenomics, targeted metabolomics, and biological assays. Mechanically, TCC exposure caused induction of intestinal aryl hydrocarbon receptor (AhR) and its transcriptional target cytochrome P4501A1 ( Cyp1a1 ) leading to dysfunction of the gut barrier and disruption of the gut microbial community. A large number of lipopolysaccharides (LPS) are released from the gut lumen into blood circulation owing to the markedly increased permeability and gut leakage. Consequently, toll-like receptor-4 (TLR4) and NF-κB signaling pathways were activated by high levels of LPS. Simultaneously, classic macrophage phenotypes were switched by TCC, shown with marked upregulation of macrophage M1 and downregulation of macrophage M2 that was accompanied by striking upregulation of proinflammatory factors such as Il-1β, Il-6, Il-17, and Tnf- α in the intestinal lamina propria. These findings provide new evidence for the TCC-induced enterotoxicity.