Metabolomics Profiling of Biological Responses to Changes in Air Pollution Levels

对空气污染水平变化的生物反应的代谢组学分析

• 批准号: 9298659
• 负责人: Lina Mu
• 金额: $ 19.28万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9298659
• 关键词: Address; Adult; Air; Air Pollutants; Air Pollution; Alpha Cell; Biological; Biological Assay; Biological Markers; Cardiovascular Diseases; Cell physiology; Clinical; Collection; Congenital Abnormality; Data; Detection; Disease; Early Diagnosis; Eicosanoids; Enrollment; Ensure; Environmental Exposure; Environmental Pollutants; Epidemiology; Evaluation; Exposure to; Fatty Acids; Female; Future; Gene Expression; Gene Proteins; Generations; Health; Human; Hypersensitivity; Inflammation; Inflammatory; Inflammatory Response; Intervention; Investigation; Link; Lipid Peroxidation; Lipid Peroxides; Malignant Neoplasms; Measures; Mediator of activation protein; Metabolic; Mission; Molecular Weight; National Institute of Environmental Health Sciences; Nature; Organ; Organism; Outcome; Oxidative Stress; Parents; Participant; Pathogenesis; Pathogenicity; Pathway Analysis; Pathway interactions; Pharmacotherapy; Pilot Projects; Process; Production; Reporter; Research; Research Design; Risk; Role; Sampling; Serum; Specimen; Sputum; Stress; Time; Tissues; United States National Institutes of Health; Urine; Validation; air pollution control; design; environmental stressor; epidemiology study; exposed human population; glutathione peroxidase; insight; interest; lipid mediator; male; metabolic profile; metabolome; metabolomics; neurodevelopment; non-smoking; novel; outcome forecast; response; tool

Abstract 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.

摘要 代谢组代表了细胞过程终产物的集合，并且是最重要的 近端报告人的身体的反应，环境暴露，疾病的进程，和药物治疗。 代谢组学已被提出作为研究各种临床结果的有力工具，包括 与空气污染暴露有关的疾病，如癌症和心血管疾病。到目前为止， 代谢组学在研究大气污染相关机制方面的应用非常有限。我们假设 空气污染水平的变化与多种途径的代谢变化有关，包括 炎症和氧化应激。代谢组学，由于其全面和公正的性质， 分析，具有发现新的生物标志物和揭示新机制的优势。 北京奥运会空气污染研究是我们在北京奥运会期间进行的一项小组研究， 实施临时空气污染管制措施。这项研究在北京之前招募了201名成年人 空气质量改善计划，并跟踪调查空气污染的短期影响 暴露在人体内。在基线时从每个参与者收集生物样本并储存， 在奥运会期间和之后。利用来自本研究的一个子集（66名参与者）的储存血清样本， 现有的研究，我们建议（1）进行脂质过氧化代谢谱的靶向测定， 炎症脂质介质（13种代谢物），以检查对空气中变化的代谢反应 在三个研究期间的污染水平，以及（2）进行非目标性的分析，使用高 通量方法（886种代谢物），以发现对剧烈变化有强烈反应的代谢物 空气污染水平，以及确定代表总体的新途径和代谢特征 代谢变化 我们已进行试验研究，探讨拟议计划的可行性。我们观察到， 多种途径的变化，包括脂肪酸脂质过氧化物和类花生酸，这与 来自我们的母体研究的结果，其中谷胱甘肽过氧化物酶（GPx）活性由空气诱导 污染暴露。我们预计，拟议的研究将提供一个使用代谢组学的例子， 研究人类暴露于空气污染，揭示脂质过氧化和炎症脂质的关键作用 调解人，并产生新的假说，有关的途径，为今后的研究。简档 探索可能会促进我们目前对人类对空气污染的整体生物反应的理解 exposure.我们预计这些发现将与未来研究的临床结果相关联。

项目成果

Biomarkers used in studying air pollution exposure during pregnancy and perinatal outcomes: a review.

• DOI: 10.1080/1354750x.2017.1339294
• 发表时间: 2017-09
• 期刊: Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals
• 作者: Desai G;Chu L;Guo Y;Myneni AA;Mu L
• 通讯作者: Mu L