The metabolome represents the collection of the end products of cellular processes, and is the most proximal reporter of the body's response to environmental exposure, disease processes, and drug therapy. Metabolomics has been put forward as a powerful tool for studying various clinical outcomes, including diseases related to air pollution exposure, such as cancer and cardiovascular diseases. So far, application of metabolomics to studying air pollution related mechanisms has been very limited. We hypothesize that changes in air pollution levels are associated with metabolic changes in multiple pathways, including inflammation and oxidative stress. Metabolomics, owing to its comprehensive and unbiased nature of analysis, has the advantage of discovering new biomarkers and revealing novel mechanisms. The Beijng Olympics Air Pollution Study is a panel study we conducted during Beijing Olympics when temporary air pollution control measures were implemented. The study enrolled 201 adults prior to Beijing's air quality improvement initiative and followed them to investigate the short-term effects of air pollution exposure in humans. Biological specimens were collected and banked from each participant at baseline, during, and after the Olympics. Utilizing stored serum samples from a subset (66 participants) of this existing study, we propose (1) to conduct a targeted assay on the metabolic profile of lipid peroxidation and inflammatory lipid mediators (13 metabolites) to examine metabolic responses to the changes in air pollution levels over the three study periods, and (2) to conduct a untargeted analysis using a high throughput approach (886 metabolites) to discover the metabolites that respond strongly to drastic changes in air pollution levels, as well as to identify novel pathways and metabolic signatures that represent overall metabolic changes. We have conducted a pilot study to explore the feasibility of the proposed project. We observed obvious changes in multiple pathways, including fatty acid lipid peroxides and eicosanoids, which are consistent with the results from our parent study in which glutathione peroxidase (GPx) activities were induced by air pollution exposure. We anticipate that the proposed study will provide an example of using metabolomics to study human exposure to air pollution, reveal the critical role of lipid peroxidation and inflammatory lipid mediators, and generate novel hypotheses regarding relevant pathways for future study. The profile exploration may advance our current understanding of overall human biological responses to air pollution exposure. We anticipate that these findings will be linked with clinical outcomes in future studies.
Our proposal is highly relevant to the mission of the NIH/National Institute of Environmental Health Sciences. Air pollution is a ubiquitous, worldwide exposure associated with various diseases. Our study will evaluate metabolic changes in response to air pollution exposure and provide insight on potential mechanisms through which air pollution may increase the risk of various diseases; moreover, the epidemiologic nature of our proposed research ensures that the data generated will be directly applicable to humans.
| Farhat, Zeinab; Browne, Richard W; Bonner, Matthew R et al. (2018) How do glutathione antioxidant enzymes and total antioxidant status respond to air pollution exposure? Environ Int 112:287-293 |
| Desai, Gauri; Chu, Li; Guo, Yanjun et al. (2017) Biomarkers used in studying air pollution exposure during pregnancy and perinatal outcomes: a review. Biomarkers 22:489-501 |
