Early-pregnancy exposure to persistent organic pollutants and bile acid alterations in relation to gestational glucose–lipid homeostasis

Persistent Organic Pollutants (POPs) are globally distributed, bioaccumulative chemicals increasingly implicated as environmental contributors to metabolic toxicity, yet the mechanistic pathways underlying their effects during early pregnancy remain poorly characterized. In this maternal cohort study, high-resolution mass spectrometry showed that women with early metabolic abnormalities carried higher serum burdens of several POP congeners, with polybrominated diphenyl ethers (PBDEs; e.g., BDE-153, BDE-154) and polychlorinated biphenyl-52 (PCB-52) showing the most consistent elevations. Targeted metabolomics further identified marked alterations of bile acid profiles: putatively protective bile acids such as glycoursodeoxycholic acid (GUDCA) (2.32 vs. 2.79 ng/mL, P < 0.05) and glycochenodeoxycholic acid (GCDCA) (2.32 vs. 4.77 ng/mL, P < 0.05) were markedly depleted in women with early metabolic abnormalities compared with those without, whereas taurine-conjugated species, including tauroursodeoxycholic acid (TUDCA), were elevated. Correlation analyses revealed inverse associations between brominated congeners and conjugated bile acids (e.g., BDE-154 and TUDCA, r = −0.29, P < 0.001), while PCB-52 was positively associated with serum cholesterol levels. In mediation analyses, GUDCA and TUDCA jointly mediated up to 24 % of the association between PBDEs and dysregulated glucose metabolism, sulfated bile acids mediated 21–25 % of PBDE–triglyceride associations and norcholic acid (NorCA) accounted for 19 % of the PCB-52–cholesterol relationship. These findings provide human evidence that maternal POP exposure is associated with perturbations in bile acid metabolism that may contribute to impaired glucose–lipid homeostasis during early pregnancy, and highlight bile acids as mechanistic mediators and potential early biomarkers of pollutant-induced metabolic toxicity. • Maternal exposure to POPs was associated with gestational diabetes mellitus. • BDE-153, BDE-154, and PCB-52 showed the strongest metabolic associations. • GDM cases had reduced GUDCA/UDCA and elevated taurine-conjugated bile acids. • GUDCA and TUDCA mediated up to 24 % of PBDE–GDM associations. • Bile acids act as mechanistic mediators of pollutant-related metabolic disruption.