Nanoplastics and triclosan co-exposure aggravates DSS-induced colitis in mice by interfering with Akkermansia muciniphila and tryptophan metabolism

The global incidence of inflammatory bowel disease (IBD) has been escalating. Recent studies have identified co-exposure to polystyrene nanoplastics (PSNP) and triclosan (TCS), two prevalent environmental pollutants, as emerging risk factors for IBD. However, the molecular mechanisms contributing to its deteriorative effect remain elusive. To explore the mechanisms, we conducted an integrative analysis of metagenomic and metabolomic data in a mouse model of colitis induced by dextran sulfate sodium (DSS) following co-exposure to PSNP and TCS. Results demonstrated that co-exposure to PSNP and TCS significantly exacerbated DSS-induced colitis, as evidenced by elevated disease activity indices and pro-inflammatory cytokine levels. Mechanistically, this aggravation correlated with a marked reduction in Akkermansia muciniphila abundance, which was further associated with the disruption of tryptophan metabolism. Specifically, the disruption of this metabolic pathway led to decreased production of two key tryptophan-derived metabolites: indole acetic acid (IAA) and indole acetamide (IAM). In-vitro experiments confirmed that co-exposure to PSNP and TCS inhibited the growth of A. muciniphila rather than affecting the integrity of intestinal epithelial cells. Additionally, IAA and IAM reduced inflammatory cytokine secretion in THP-1 cells. These findings suggest that the reduction in A. muciniphila abundance might decrease the production of IAA and IAM by disrupting tryptophan metabolism. This disruption ultimately contributes to the inflammatory response induced by co-exposure to PSNP and TCS. Our study offers a novel insight into microbiota-host interactions and potential therapeutic targets for intestinal disease.