2,3,7,8-tetrachlorodibenzofuran modulates intestinal microbiota and tryptophan metabolism in mice

Persistent organic pollutants (POPs) are known to disrupt gut microbiota composition and host metabolism, primarily through dietary exposure. In this study, we investigate the impact of 2,3,7,8-tetrachlorodibenzofuran (TCDF) on gut microbiota and host metabolic processes. RNA-seq analysis revealed that TCDF exposure significantly affected tryptophan metabolism, lipid metabolic pathways, and immune system function. Metagenomic and metabolomic analyses further showed that TCDF reduced the abundance of Mucispirillum schaedleri and levels of two key tryptophan metabolites, indole-3-carboxaldehyde (3-IAld) and Indole acrylic acid (IA). Supplementation with 3-IAld and IA alleviated TCDF-induced liver toxicity in mouse, as evidenced by reduced Cyp1a1 expression, and mitigated intestinal inflammation, reflected by lower pro-inflammatory cytokines (Ifn-γ and Il-1β) in the colon. Additionally, 3-IAld and IA supplementation enhanced intestinal barrier function, as demonstrated by increased Mucin 2 (MUC2) expression in the gut mucosa of mouse. These findings suggest that TCDF exposure disrupts the gut microbiome and host metabolic balance, and highlight the potential therapeutic role of tryptophan-derived metabolites in mitigating environmental pollutant-induced damage.