The impact of ambient air pollution on the human blood metabolome

Background: Biological perturbations caused by air pollution might be reflected in the compounds present in blood originating from air pollutants and endogenous metabolites influenced by air pollution (defined here as part of the blood metabolome). We aimed to assess the perturbation of the blood metabolome in response to short term exposure to air pollution. Methods: We exposed 31 healthy volunteers to ambient air pollution for 5 h. We measured exposure to particulate matter, particle number concentrations, absorbance, elemental/organic carbon, trace metals, secondary inorganic components, endotoxin content, gaseous pollutants, and particulate matter oxidative potential. We collected blood from the participants 2 h before and 2 and 18 h after exposure. We employed untargeted metabolite profiling to monitor 3873 metabolic features in 493 blood samples from these volunteers. We assessed lung function using spirometry and six acute phase proteins in peripheral blood. We assessed the association of the metabolic features with the measured air pollutants and with health markers that we previously observed to be associated with air pollution in this study. Results: We observed 89 robust associations between air pollutants and metabolic features two hours after exposure and 118 robust associations 18 h after exposure. Some of the metabolic features that were associated with air pollutants were also associated with acute health effects, especially changes in forced expiratory volume in 1 s. We successfully identified tyrosine, guanosine, and hypoxanthine among the associated features. Bioinformatics approach Mummichog predicted enriched pathway activity in eight pathways, among which tyrosine metabolism. Conclusions: This study demonstrates for the first time the application of untargeted metabolite profiling to assess the impact of air pollution on the blood metabolome.