Cadmium sulfide nanoparticles exacerbate colitis via Faecalibaculum rodentium-mediated modulation of the indole-3-lactic acid-Th17 axis.

Abstract

With the increasing application of cadmium sulfide nanoparticles (CdS-NPs), their potential adverse effects on intestinal health have attracted growing attention. However, the impact of CdS-NPs exposure on inflammatory bowel disease (IBD) and the underlying mechanisms remain unclear. Here, we demonstrate that daily oral gavage exposure to 1 mg/kg CdS-NPs for 4 weeks or 11 weeks alone did not induce apparent colonic inflammation in healthy mice but exacerbated both acute and chronic DSS-induced colitis, as evidenced by severe weight loss, increased disease activity, colon shortening, tissue damage, and immune infiltration. Integrated gut microbiota profiling and metabolomic analysis revealed that CdS-NPs markedly reduced the abundance and tryptophan-metabolizing capacity of Faecalibaculum rodentium (F. rodentium), leading to impaired indole-3-lactic acid (ILA) production. F. rodentium administration significantly alleviated CdS-NPs-aggravated DSS-induced colitis and restored serum ILA levels, accompanied by suppression of Th17 responses. Consistently, exogenous ILA treatment attenuated intestinal inflammation and suppressed Th17/IL-17 responses in vivo and inhibited Th17 differentiation in CD4+ T cells in vitro. Collectively, our findings identify microbial tryptophan metabolism and IL-17 signaling as critical mediators of intestinal inflammatory sensitization associated with CdS-NPs exposure and highlight the F. rodentium-ILA axis as a potential intervention target for CdS-NPs-induced intestinal inflammation.

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