Untargeted Metabolomics Reveals Metabolic Perturbations in Community-Dwelling Elderly Exposed to PM_2.5-Bound Ester...

Background/Objectives: Ambient fine particulate matter (PM_2.5) 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 PM_2.5-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 PM_2.5 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 PM_2.5 concentration was 38.06 μg/m³, with ester compounds dominating the chemical composition. Twenty high-concentration non-target esters were prioritized for analysis. PM_2.5 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 PM_2.5-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 PM_2.5 risk assessments and develop targeted interventions for vulnerable aging populations.