Gestational/lactational tetrachlorobisphenol A exposure induces gut microbiota dysbiosis and metabolic disruption: Implications for intergenerational health risks

Tetrachlorobisphenol A (TCBPA), a widely used chemical on material modification and flame retardant synthesis, bioaccumulates through the food chain and presents significant health concerns. However, the long-term effects of TCBPA exposure on gut microbial ecosystems and their metabolic functions remain poorly characterized. The present study developed a gestational/lactational exposure model in rats to systematically evaluate the impact on maternal and offspring gut microbiomes and fecal metabolomes by TCBPA exposure. 16S rRNA sequencing analysis demonstrated that TCBPA exposure significantly reduced both α-diversity indices and the relative abundance of critical short-chain fatty acid (SCFA)-producing genera, including Lachnospiraceae, Ruminococcus, Lactobacillus, and the unclassified norank_o_Clostridia_UCG-014. These results suggested that TCBPA perturbs gut microbiota by reducing key SCFA-producing bacteria. These microbial alterations were accompanied by corresponding decreases in fecal SCFA levels, indicating impaired microbial metabolic capacity. Metabolomics analysis revealed 18 metabolic pathways significantly affected by TCBPA, with the most marked changes in the arginine and proline metabolism pathway and the primary bile acid biosynthesis pathway. A strong correlation between gut microbiota and SCFA/metabolite levels suggests that alterations in gut microbiota may influence fecal metabolite metabolism. These findings collectively demonstrate that gestational/lactational TCBPA exposure induces persistent disruptions in gut microbial communities and their metabolic functions, which may underlie observed intergenerational health effects.