The Saliva Metabolome for Monitoring the Impact of Air Pollution Exposure on Human Health

Abstract

Background. Blood metabolomics is a sensitive tool for measuring complex environmental mixtures and biological responses. It is possible that saliva, a filtrate of blood, may serve as an alternative, non-invasive biospecimen to blood plasma, although its use for specific metabolomic applications requires validation. Methods. To compare metabolomic features in saliva and plasma, we examined longitudinal biospecimens from 53 college students living at various distances to a traffic hotspot over four months, as well as their exposure to traffic-related air pollutants (TRAP). All samples were analyzed using liquid chromatography with high-resolution mass spectrometry. We compared metabolic features detected in saliva and plasma and examined the impacts of TRAP on saliva and plasma metabolome using an advanced untargeted Metabolome Wide Association Study workflow. Results. Using hydrophilic interaction liquid chromatography with positive electrospray ionization, we extracted a total of 13,604 metabolic features from 156 pairs of saliva and plasma samples, with 5,699 in plasma and 7,905 in saliva. We detected 1,975 unique metabolic features in both plasma and saliva, with a Pearson’s correlation coefficient of the overlapping features of 0.53. Using linear mixed effect models, 727 and 466 overlapping features were found to be associated with at least one or more TRAP indicators in plasma and saliva, respectively, with 81 features consistently significant in both biometrics. Four and eight biological pathways were independently associated with TRAPs among saliva and plasma features, respectively, where carnitine shuttle and lysine metabolism are the commonly perturbed pathway in both biometrics. Conclusions. With moderate-to-strong correlation with plasma metabolome, and similar patterns of perturbed metabolic pathways, we found saliva to serve as a moderately sensitive, non-invasive biometric for short-term exposure to elevated air pollution. While providing a less comprehensive signal of response, these results are promising and supportive of future validation for its use in environmental exposure applications.