Long-term developmental alterations in intestinal microbiota, metabolism, and T-cell homeostasis in offspring rats following maternal tetrabromobisphenol A exposure

Altered Treg/Th17 balance indicated disturbed T-cell homeostasis in offspring. • Maternal TBBPA exposure was associated with colonic inflammation in F1 offspring. • Maternal TBBPA exposure was associated with altered gut microbiota and SCFA profiles. • Exploratory metabolomics identified bile acid biosynthesis as a top-ranked pathway. Tetrabromobisphenol A (TBBPA), a widely used brominated flame retardant, has been associated with adverse health effects. An exploratory NHANES analysis of urinary bisphenol A (BPA) was performed to provide general population-level context for bisphenol-related metabolic and inflammatory associations because urinary TBBPA measurements were unavailable. We investigated whether maternal TBBPA exposure (170 mg·kg⁻¹·day⁻¹) was associated with developmental alterations in offspring intestinal homeostasis. Maternal TBBPA exposure was associated with colonic inflammatory features, increased pro-inflammatory cytokine expression, and reduced Treg/Th17 ratios in F1 offspring. Gut microbiota composition was altered, including phylum- and genus-level differences, accompanied by altered fecal short-chain fatty acid composition and concentrations. Exploratory untargeted metabolomics identified nominally altered MS/MS-supported putatively annotated metabolite features. Primary bile acid biosynthesis had the lowest raw pathway-level p value and was therefore considered the top-ranked exploratory pathway, although no pathway remained significant after pathway-level FDR correction. Collectively, maternal TBBPA exposure was associated with developmental alterations in gut microbiota composition, microbial metabolites, fecal metabolic profiles, and intestinal T-cell homeostasis in F1 offspring, providing insight into the potential developmental intestinal immunotoxicity of TBBPA. Download: Download high-res image (223KB) Download: Download full-size image Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant that is now ubiquitously detected in environmental media, wildlife, and humans. Due to its persistence, widespread use, and potential for maternal transfer, TBBPA may pose sustained risks during sensitive developmental periods. Increasing evidence links TBBPA exposure to developmental, metabolic, and immune-related adverse effects, raising concern over its long-term health implications. Its environmental ubiquity and potential developmental toxicity underscore the need for continued monitoring, exposure control, and strengthened environmental risk assessment.