Duration of PM2.5 exposure and alterations in the serum metabolome

Abstract

BACKGROUND AND AIM: Acute and chronic fine particulate matter (PM₂.₅) exposures have been linked to negative outcomes; however, the underlying biological pathways remain unclear. Metabolomics can describe these biological pathways yet previous studies have only focused on a singular PM₂.₅ exposure window. We sought to compare alterations in the serum metabolome by comparing various short- and long-term residential PM₂.₅ exposures. METHODS: Participants were women undergoing in vitro fertilization at a New England fertility clinic (n=200). Women provided their residential address at enrollment and a blood sample during controlled ovarian stimulation. Residential PM₂.₅ exposure was estimated using a validated hybrid model. We derived five PM₂.₅ exposure windows: 1, 2, and 3 days, 2 weeks, and 3 months prior to blood collection. We utilized liquid chromatography with high resolution mass spectrometry and two columns (C18 negative and HILIC positive) to identify metabolites. We used generalized linear models to test for significant associations between each metabolomic feature and exposure window after adjusting for potential confounders. Significant metabolites (p0.005) were used for pathway analysis and metabolite identification using level-1 evidence. RESULTS:We identified 17 pathways related to amino acid, lipid, energy, and nutrient metabolism that were solely associated with acute PM₂.₅ exposure. Fifteen pathways, mostly, pro-inflammatory, anti-inflammatory, amino acid, and energy metabolism, were solely associated with long-term PM₂.₅ exposure. Seven pathways were associated with the majority of exposure windows and were mostly related to anti-inflammatory and lipid metabolism. Using level-1 evidence, we identified 12 unique metabolites associated with PM₂.₅ exposures of varying duration, 3 of which were part of identified metabolic pathways. CONCLUSIONS:We identified significant serum metabolites and metabolic pathways uniquely associated with acute versus chronic PM₂.₅ exposure. These different biologic pathways may help explain differences seen in disease states when investigating different durations of PM₂.₅ exposure and may inform biomarker studies examining PM₂.₅ exposure. KEYWORDS: Biomarkers of exposure, Long-term exposure, Particulate matter, Short-term exposure