Abstract

Growing evidence suggests that exposure to endocrine disrupting chemicals, such as per- and polyfluoroalkylsubstances(PFAS) interfere with host metabolism and affect development of metabolic diseases. In a cohort of 264 Danes we measured serum bile acids (BAs), PFAS and additional twenty-seven environmental toxicants as well as gut microbiome composition by shotgun metagenomic sequencing. We found that blood concentrations of widespread environmental toxicants such as PFAS associate with body fat accumulation and insulin resistance in a sexually dimorphic manner. These findings were substantiated by the outcome of the murine exposure study. In another study, we investigated potential role of exposure to PFAS in the developmental origin of metabolic disease. Human fetal livers between 11-19 weeks of gestation were analyzed by both targeted and untargeted metabolomic analyses of lipids, polar metabolites, BAs and PFAS. Several amino acids, fatty acids and sugar derivatives in fetal livers were inversely associated with PFAS exposure, while the glycolithocholic acid was markedly positively associated with all quantified PFAS. Identification of metabolic perturbations in the human fetus associated with PFAS exposure demonstrates that environmental exposure and its potential harmful impacts start in utero. These effects of PFAS in the fetus, particularly with respect to lipid and BA metabolism, might be responsible for reported adverse health effects during early life.