Non-targeted metabolomics in evaluating alterations associated with per-fluoroalkyl and polyfluoroalkyl substances (PFAS) exposure in human studies: a scoping review

Abstract

BACKGROUND AND AIM: Non-targeted metabolomics has been incorporated into recent epidemiological studies to investigate metabolic mechanisms underlying adverse health effects of per-fluoroalkyl and polyfluoroalkyl substances (PFAS) exposure. The purpose of this review is to summarize the application of non-targeted metabolomics in epidemiological studies that assessed metabolite and metabolic pathway alterations associated with PFAS exposure. METHODS: We performed a scoping review of human studies that conducted non-targeted metabolomics and PFAS analyses including original articles published in PubMed before March 1, 2021. We summarized the study characteristics and the metabolites and metabolic pathways reported to be associated with PFAS exposure. RESULTS:Nine human studies published between 2018 to 2021 were identified. The study sample ranged from 40 to 965 participants, including children and adolescents (n=3), adults (n=3), or pregnant women (n=3). Health outcomes involved included non-alcoholic liver, type 2 diabetes and other cardiometabolic outcomes. Liquid chromatography–mass spectrometry was the primary analytical platform for PFAS measurement and non-targeted metabolomics. PFAS levels were measured in plasma (n=5) or serum (n=4), while the metabolomic profiles were generated in plasma (n=5), serum (n=3), or urine (n=1). The most studied PFAS compounds were PFOS (n=9), PFOA (n=8), PFHxS (n=8), PFNA (n=5), and PFAS mixtures (n=4). Among seven studies that conducted pathway enrichment analysis, the most commonly reported metabolic pathways affected by multiple PFAS compounds were lipid metabolism, including glycerophospholipid, glycosphingolipid, and linoleate metabolism, followed by amino acid-related pathways, such as urea cycle/amino group metabolism, alanine and aspartate metabolism, and beta-alanine metabolism. Other reported metabolomics alterations possibly associated with PFAS include carbohydrate-related metabolism, xenobiotic (drug) related metabolism, and vitamin metabolism. CONCLUSIONS:Multiple PFAS exposures were associated with alterations to lipid- or amino acid-related metabolism in human studies that used non-targeted metabolomics. Whether these PFAS-associated biological changes lead to adverse health risks requires further research. KEYWORDS: PFAS, Metabolomics, Chemical exposures, Obesity and metabolic disorders