Cord blood metal(loid) concentrations and bile acid profiles: Insights from mixture analysis

Bile acids (BAs) are essential signaling molecules that regulate metabolic and inflammatory processes. However, epidemiological evidence on the influence of metal(loid) mixtures on BA profiles remains scarce, particularly among newborns. This study investigated the associations between cord blood metal(loid) concentrations and BA levels in 224 newborns. Single metal(loid) effects were assessed using multiple linear regression (MLR), whereas mixture effects were examined by Bayesian kernel machine regression (BKMR) and Bayesian weighted quantile sum regression (BWQS) models. In BKMR, cord blood metal(loid) mixtures were positively associated with taurocholic acid (TCA), with lead (Pb) emerging as the dominant contributor (groupPIP = 0.85; condPIP = 0.83). In BKMR single-exposure response analyses, increasing Pb concentrations was associated with a 13.61-14.28% increase in TCA when the other metal(loid)s were held at the 25th, 50th, and 75th percentiles. Consistently, BWQS showed that each ln-unit increase in the mixture index was associated with a 13.98% increase in TCA (95% CI: 0.24%, 29.40%). In addition, BKMR suggested inverse associations of Se with taurochenodeoxycholic acid (TCDCA), taurodeoxycholic acid (TDCA), and tauroursodeoxycholic acid (TUDCA), whereas MLR suggested inverse associations of Tl with glycodeoxycholic acid (GDCA) and glycoursodeoxycholic acid (GUDCA); however, these findings were not consistently supported across analytical approaches. Exploratory sex-stratified analyses suggested a positive mixture-TCA association among female infants. Our findings provide novel evidence that metal(loid) mixtures may be associated with altered cord blood BA profiles at birth and highlight the need for further investigation into their potential metabolic implications.