Metabolomics & Air Pollution Exposure

Ambient air pollutants are well known risk factors for childhood asthma, COVID-19 incidence, and childhood obesity. In one of our studies concerning childhood asthma, we aimed to integrate transcriptome and untargeted metabolome to identify dysregulated genetic and metabolic pathways that are associated with exposures to a mixture of ambient and traffic-related air pollutants among adults with asthma history. Participants’ exposures to regional air pollutants (NO2, O3, PM10, PM2.5) and near-roadway air pollutants averaged at one month and one year before study visit were estimated based on residential addresses. Network analysis found that exposures to air pollutants mixture were connected to 357 gene markers and 92 metabolites. One-year and one-month averaged PM2.5 and NO2 were associated with several amino acids related to serine, glycine, and beta-alanine metabolism. These results indicate that exposures to various air pollutants are associated with altered genetic and metabolic pathways that affect anti-oxidative capacity and immune response and can potentially contribute to asthma-related pathophysiology.

 Jiawen Liao, Roya Gheissari, Duncan C. Thomas, Frank D. Gilliland, Fred Lurmann, Khandaker Talat Islam, Zhanghua Chen,Transcriptomic and metabolomic associations with exposures to air pollutants among young adults with childhood asthma history, Environmental Pollution, Volume 299, 2022, 118903, ISSN 0269-7491,

Air pollution exposure has been associated with increased risk of COVID-19 incidence and mortality by ecological analyses. Few studies have investigated the specific effect of traffic-related air pollution on COVID-19 severity. In another study of ours, we investigated the associations of near-roadway air pollution (NRAP) exposure with COVID-19 severity and mortality using individual-level exposure and outcome data. After analyzing retrospective records of diagnosed COVID-19 patients from Kaiser Permanente Southern California, traffic- related air pollution has been associated with a higher risk of COVID-19 incidence, severity and mortality. Like PM2.5 and NO2, traffic-related air pollution has been shown to increase systemic inflammation, which may play a role in the mechanism of severe COVID-19. (Lanki et al., 2015Rich et al., 2012

Chen Z, Huang BZ, Sidell MA, et al. Near-roadway air pollution associated with COVID-19 severity and mortality – Multiethnic cohort study in Southern California. Environment International. 2021 Dec;157:106862. DOI: 10.1016/j.envint.2021.106862. PMID: 34507232; PMCID: PMC8416551.

Several large longitudinal studies showed that both regional AP and NRAP were associated with increased type 2 diabetes incidence and mortality. Results from studies in both children and adults, including my previous work, indicated that both short- and long-term exposures to regional AP such as particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) and nitrogen dioxide (NO2) adversely effected key type 2 diabetes-related pathways such as glucose metabolism, insulin resistance, and dyslipidemia.

A series of metabolomics studies have linked changes in metabolic profiles with increased adiposity, including visceral and liver fat. Recent studies in human and mice revealed that short-term exposures to regional AP (e.g., NO2, ozone (O3), and PM2.5) and traffic emissions were associated with significant changes in metabolism of fatty acid and amino acid.

Inhalation of AP can cause inflammatory activation in the lung and the inflammation can spill over systematically. Low-grade systematic inflammation is also an important feature of obesity and type 2 diabetes. Therefore, chronic systemic inflammation may play an important role in the impact of AP exposures on obesity and metabolic dysfunction.

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