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

Abstract

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.