Metabolomic signatures of the short-term exposure to air pollution and temperature

Background: Short-term exposures to air pollution and temperature have been reported to be associated with inflammation and oxidative stress. However, mechanistic understanding of the affected metabolic pathways is still lacking and literature on the short-term exposure of air-pollution on the metabolome is limited. Objectives: We aimed to determine changes in the plasma metabolome and associated metabolic pathways related to short-term exposure to outdoor air pollution and temperature. Methods: We performed mass-spectrometry based untargeted metabolomic profiling of plasma samples from a large and well-characterized cohort of men (Normative Aging Study) to identify metabolic pathways associated with short-term exposure to PM2.5, NO2, O-3, and temperature (one, seven-, and thirty-day average of address specific predicted estimates). We used multivariable linear mixed-effect regression and independent component analysis (ICA) while simultaneously adjusting for all exposures and correcting for multiple testing. Results: Overall, 456 white men provided 648 blood samples, in which 1158 metabolites were quantified, between 2000 and 2016. Average age and body mass index were 75.0 years and 27.7 kg/m(2), respectively. Only 3% were current smokers. In the adjusted models, NO2, and temperature showed statistically significant associations with several metabolites (19 metabolites for NO2 and 5 metabolites for temperature). We identified six metabolic pathways (sphingolipid, butanoate, pyrimidine, glycolysis/gluconeogenesis, propanoate, and pyruvate metabolisms) perturbed with short-term exposure to air pollution and temperature. These pathways were involved in inflammation and oxidative stress, immunity, and nucleic acid damage and repair. Conclusions: This is the first study to report an untargeted metabolomic signature of temperature exposure, the largest to report an untargeted metabolomic signature of air pollution, and the first to use ICA. We identified several significant plasma metabolites and metabolic pathways associated with short-term exposure to air pollution and temperature; using an untargeted approach. Those pathways were involved in inflammation and oxidative stress, immunity, and nucleic acid damage and repair. These results need to be confirmed by future research.