ArticleThe Science of the total environment2025
High-dimensional mediation analysis to elucidate the role of metabolites in the association between PFAS exposure and reduced SARS-CoV-2 IgG in pregnancy.
Article in The Science of the total environment, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Analysis and fate of per- and polyfluoroalkyl substances (PFAS) in the global aquatic environment: perspectives and combined risks with microplastics.Analytical and bioanalytical chemistry · 2026Review
- Prenatal PFAS exposure and offspring health: evidence review and implications for intergenerational risk assessment.Frontiers in public health · 2026Review
- Per- and Polyfluoroalkyl Substances (PFAS): History, Current Concerns, and Future Outlook.Molecules (Basel, Switzerland) · 2025Review
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14 authors.
Funding
Abstract
We previously found that per- and polyfluoroalkyl substances (PFAS) mixture exposure is inversely associated with SARS-CoV-2 IgG (IgG) antibody levels in pregnant individuals. Here, we aim to identify metabolites mediating this relationship to elucidate the underlying biological pathways. This cross-sectional study included 59 pregnant participants from a US-based pregnancy cohort. Untargeted metabolomic profiling was performed using Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS), and Weighted Quantile Sum (WQS) regression was applied to assess the PFAS and metabolites mixture effects on IgG. Metabolite indices positively or negatively associated with IgG levels were constructed separately and their mediation effects were examined independently and jointly. The PFAS-index was negatively associated with IgG levels (beta = -0.315, p < 0.001), with PFHpS and PFHxS as major contributors. Two metabolites-indices were constructed, one positively (beta = 1.249, p < 0.001) and one negatively (beta = -1.200, p < 0.001) associated with IgG. Key contributors for these indices included trigonelline, adipate, p-octopamine, and n-acetylproline. Analysis of a single mediator showed that 74.6 % (95 % CI: 45.9 %, 98.0 %) and 68.6 % (95 % CI: 41.8 %, 94.1 %) of the PFAS index-IgG total effect were mediated by the negative and positive metabolites-indices, respectively. Joint analysis of the metabolites-indices indicated a cumulative mediation effect of 83.8 % (95 % CI: 58.1 %, 98.7 %). Enriched pathways associated with these metabolites-indices were phenylalanine, tyrosine, and tryptophan biosynthesis and arginine metabolism. We observed significant mediation effects of plasma metabolites on the PFAS-IgG relationship, suggesting that PFAS is associated with alteration in the balance of plasma metabolites that contributes to reduced plasma IgG production.
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