Plasma concentrations of per- and polyfluoroalkyl substances are associated with perturbations in lipid and amino acid metabolism

Exposure to per- and polyfluoroalkyl substances (PFAS) through the environment can lead to harmful health outcomes and the development of disease. However, little is known about how PFAS impact underlying biology that contributes to these adverse health effects. The metabolome represents the end product of cellular processes and has been used previously to understand physiological changes that lead to disease. In this study, we investigated whether exposure to PFAS was associated with the global, untargeted metabolome. In a cohort of 459 pregnant mothers and 401 children, we quantified plasma concentrations of six individual PFAS- PFOA, PFOS, PFHXS, PFDEA, and PFNA- and performed plasma metabolomic profiling by UPLC-MS. In adjusted linear regression analysis, we found associations between plasma PFAS and perturbations in lipid and amino acid metabolites in both mothers and children. In mothers, metabolites of 19 lipid pathways and 8 amino acid pathways were significantly associated with PFAS exposure at an FDR