Untargeted Metabolomics Reveals Metabolic Perturbations in Community-Dwelling Elderly Exposed to PM2.5-Bound Ester Compounds

Abstract

Background/Objectives: Ambient fine particulate matter (PM2.5) poses significant health risks to older adult populations, yet the specific contributions of its chemical constituents, particularly non-phthalate and non-organophosphate ester compounds, remain poorly understood. This study aimed to elucidate the mechanistic links between PM2.5-bound ester exposures and metabolic pathway alterations in elderly individuals. Methods: A total of 258 elderly residents aged 60 years or older from Fuzhou, China, were recruited. Personal PM2.5 exposure was monitored over 72 h using UPAS V2 samplers, with chemical components analyzed via gas chromatography–mass spectrometry (GC–MS). Plasma metabolomic profiling was conducted using liquid chromatography–mass spectrometry (LC–MS), and metabolic pathway enrichment was performed using MetaboAnalyst 5.0. Linear regression models adjusted for covariates (age, sex, BMI, lifestyle factors) assessed associations between ester exposures and metabolite abundance. Results: The mean PM2.5 concentration was 38.06 μg/m3, with ester compounds dominating the chemical composition. Twenty high-concentration non-target esters were prioritized for analysis. PM2.5 ester exposure was associated with alterations in key metabolic pathways, including steroid biosynthesis, glycolysis/gluconeogenesis, glycerophospholipid metabolism, and purine/pyrimidine metabolism. When interpreted alongside prior epidemiological evidence, these alterations represent putative links to increased risks of insulin resistance, cardiovascular dysfunction, and metabolic syndrome—relationships that require confirmation in prospective cohort studies and controlled toxicological experiments. Conclusions: Putatively annotated PM2.5-bound ester compounds, particularly non-regulated subclasses, are associated with systemic metabolic alterations in older adults, coincident with perturbations in steroid and lipid metabolism. While these findings are exploratory and hypothesis-generating, they highlight the need to incorporate specific ester profiles into PM2.5 risk assessments and develop targeted interventions for vulnerable aging populations.