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Non-targeted metabolomics and associations with per- and polyfluoroalkyl substances (PFAS) exposure in humans: A scoping review
Open accessAbstract
OBJECTIVE: To summarize the application of non-targeted metabolomics in epidemiological studies that assessed metabolite and metabolic pathway alterations associated with per- and polyfluoroalkyl substances (PFAS) exposure. RECENT FINDINGS: Eleven human studies published before April 1st, 2021 were identified through database searches (PubMed, Dimensions, Web of Science Core Collection, Embase, Scopus), and citation chaining (Citationchaser). The sample sizes of these studies ranged from 40 to 965, involving children and adolescents (n = 3), non-pregnant adults (n = 5), or pregnant women (n = 3). High-resolution liquid chromatography-mass spectrometry was the primary analytical platform to measure both PFAS and metabolome. PFAS were measured in either plasma (n = 6) or serum (n = 5), while metabolomic profiles were assessed using plasma (n = 6), serum (n = 4), or urine (n = 1). Four types of PFAS (perfluorooctane sulfonate(n = 11), perfluorooctanoic acid (n = 10), perfluorohexane sulfonate (n = 9), perfluorononanoic acid (n = 5)) and PFAS mixtures (n = 7) were the most studied. We found that alterations to tryptophan metabolism and the urea cycle were most reported PFAS-associated metabolomic signatures. Numerous lipid metabolites were also suggested to be associated with PFAS exposure, especially key metabolites in glycerophospholipid metabolism which is critical for biological membrane functions, and fatty acids and carnitines which are relevant to the energy supply pathway of fatty acid oxidation. Other important metabolome changes reported included the tricarboxylic acid (TCA) cycle regarding energy generation, and purine and pyrimidine metabolism in cellular energy systems. CONCLUSIONS: There is growing interest in using non-targeted metabolomics to study the human physiological changes associated with PFAS exposure. Multiple PFAS were reported to be associated with alterations in amino acid and lipid metabolism, but these results are driven by one predominant type of pathway analysis thus require further confirmation. Standardizing research methods and reporting are recommended to facilitate result comparison. Future studies should consider potential differences in study methodology, use of prospective design, and influence from confounding bias and measurement errors.
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“Comprehensive metabolomic investigations reveal that PFASs exposure alters key metabolic pathways, including amino acid, nucleotide, carbohydrate, and vitamin metabolism [112], disrupting mitochondrial function and cellular energy homeostasis, particularly among children and adolescents with chronic exposure [113].”
From Exposure to Per- and Polyfluoroalkyl Substances (PFASs) in Healthcare: Environmental and Clinical Insights (2025) · cites this paper as [113]
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Metadata
- Authors
- Guo, P., Furnary, T., Vasiliou, V., Yan, Q., Nyhan, K., Jones, D. P., Johnson, C. H., & Liew, Z.
- Affiliations
- Yale University (US)
- University of California, Los Angeles (US)
- Emory University (US)
- Corresponding author
- Liew, Zeyan
- ORCID
- Venue
- Environment International
- Publisher
- Elsevier BV
- Published
- 2022-04
- Volume
- 162
- Pages
- 107159
- ISSN
- 0160-4120 (ISSN-L)
- PMC
- PMC8969205
- OpenAlex
- W4214507826
- Cited by
- 145
- References
- 145
- Citations by year
- 2026: 33 · 2025: 44 · 2024: 33 · 2023: 28 · 2022: 7
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Environment International (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- China Scholarship Council
- National Institutes of Health
- National Cancer Institute (K12CA215110)
- National Institute of Environmental Health Sciences (R00ES026729)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Health, Environment, Cognitive Aging
- Keywords
- per- and polyfluoroalkyl substances, PFAS exposure, untargeted metabolomics, tryptophan metabolism, urea cycle, lipid metabolism, glycerophospholipid metabolism, fatty acids, L-carnitine, TCA cycle, purine and pyrimidine metabolism, perfluorooctanoic acid, PFOS, PFHxS, perfluorononanoic acid, PFAS mixtures, children and adolescents, pregnant women
- MeSH terms
- Adolescent, Adult, Child, Environmental Pollutants, Female, Fluorocarbons, Humans, Pregnancy, Prospective Studies, Alkanesulfonic Acids, Lipid Metabolism, Metabolomics
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