Integrated Exposomics and Metabolomics Reveal Lipid-Mediated Associations of Trace Element and PFAS Co-Exposure with Chronic Cerebral Ischemia
6 affiliations
- 1School of Public Health, Health Science Center, Ningbo University, Ningbo 315211, China
- 2Faculty of Electrical Engineering and Computer Science, Ningbo University, Ningbo 315211, China
- 3Zhejiang Engineering Research Center of Advanced Mass Spectrometry and Clinical Application, Institute of Mass Spectrometry, Ningbo University, Ningbo 315211, China
- 4The First Affiliated Hospital of Ningbo University, Ningbo 315020, China
- 5Reference Laboratory, Medical System Biotechnology Co., Ltd., Ningbo 315104, China
- 6Ningbo Municipal Center for Disease Control and Prevention, Ningbo 315012, China
Abstract
Background/Objectives: The relationship of combined trace-element and per- and polyfluoroalkyl substance (PFAS) exposure with chronic cerebral ischemia (CCI), and the metabolic changes accompanying such exposure, have not been well characterized. We therefore combined exposure assessment with metabolomic profiling to examine pollutant mixtures associated with CCI and to identify candidate metabolic intermediates. Methods: The analysis included 170 participants in a case–control design (85 CCI cases and 85 controls). Plasma was assayed for 19 trace elements and 22 PFASs, together with nontargeted metabolites. Individual and mixture associations were examined using multivariable logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression. Pathway and mediation ansalyses were then used to explore metabolic links. Results: After Benjamini–Hochberg correction, PFNA remained significant in the continuous and upper-quartile analyses, while exposure trends remained significant for PFBS, PFNA, and PFUdA. The mixture analyses also indicated an overall association with CCI, with PFNA making a prominent contribution and showing interaction with As. Metabolomic analysis yielded 41 nominally selected candidate metabolites, many of which were lipid-related. Five lipid candidates showed indirect effects that remained significant after correction across the five mediation tests: Propionylcarnitine, Linoelaidyl carnitine, LysoPC (18:1) isomer 1, LysoPE (22:5), and PE (38:3). Conclusions: The results link CCI with concurrent environmental exposures and indicate that changes in acylcarnitine and glycerophospholipid metabolism may lie on important biological pathways connecting exposure with disease.
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BibTeX
@article{yu2026integrated,
title = {{Integrated Exposomics and Metabolomics Reveal Lipid-Mediated Associations of Trace Element and PFAS Co-Exposure with Chronic Cerebral Ischemia}},
author = {Jiajun Yu and Chunlan Tang and Jiancheng Yu and Chenting Wang and Jinyan Xu and Min Shen and Qiaoli Qiu and Shuang Wang and Jinyue Zhou and Hang Hong},
journal = {Metabolites},
year = {2026},
month = nov,
doi = {10.3390/metabo16110862},
url = {https://www.mdpi.com/2218-1989/16/11/862},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrated Exposomics and Metabolomics Reveal Lipid-Mediated Associations of Trace Element and PFAS Co-Exposure with Chronic Cerebral Ischemia
AU - Jiajun Yu
AU - Chunlan Tang
AU - Jiancheng Yu
AU - Chenting Wang
AU - Jinyan Xu
AU - Min Shen
AU - Qiaoli Qiu
AU - Shuang Wang
AU - Jinyue Zhou
AU - Hang Hong
PY - 2026
DA - 2026/11/08
JO - Metabolites
DO - 10.3390/metabo16110862
UR - https://www.mdpi.com/2218-1989/16/11/862
AB - Background/Objectives: The relationship of combined trace-element and per- and polyfluoroalkyl substance (PFAS) exposure with chronic cerebral ischemia (CCI), and the metabolic changes accompanying such exposure, have not been well characterized. We therefore combined exposure assessment with metabolomic profiling to examine pollutant mixtures associated with CCI and to identify candidate metabolic intermediates. Methods: The analysis included 170 participants in a case–control design (85 CCI cases and 85 controls). Plasma was assayed for 19 trace elements and 22 PFASs, together with nontargeted metabolites. Individual and mixture associations were examined using multivariable logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression. Pathway and mediation ansalyses were then used to explore metabolic links. Results: After Benjamini–Hochberg correction, PFNA remained significant in the continuous and upper-quartile analyses, while exposure trends remained significant for PFBS, PFNA, and PFUdA. The mixture analyses also indicated an overall association with CCI, with PFNA making a prominent contribution and showing interaction with As. Metabolomic analysis yielded 41 nominally selected candidate metabolites, many of which were lipid-related. Five lipid candidates showed indirect effects that remained significant after correction across the five mediation tests: Propionylcarnitine, Linoelaidyl carnitine, LysoPC (18:1) isomer 1, LysoPE (22:5), and PE (38:3). Conclusions: The results link CCI with concurrent environmental exposures and indicate that changes in acylcarnitine and glycerophospholipid metabolism may lie on important biological pathways connecting exposure with disease.
SN - 2218-1989
ER -