Metabolomics Profiling of Biological Responses to Changes in Air Pollution Levels

摘要 代谢组代表细胞过程的最终产物的集合，并且是最 近端报道了人体对环境暴露、疾病过程和药物治疗的反应。 代谢组学已被认为是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，申请 代谢组学对空气污染相关机制的研究一直非常有限。我们假设 空气污染水平的变化与多个途径的新陈代谢变化有关，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的机制的优势。 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，当时 实施大气污染临时治理措施。这项研究在北京之前招募了201名成年人 空气质素改善计划，并跟随他们调查空气污染的短期影响 在人类身上暴露。在基线时收集每个参与者的生物样本并将其储存， 在奥运会期间和之后。利用来自这一子集(66名参与者)的存储血清样本 在已有研究的基础上，我们建议：(1)对脂质过氧化的代谢情况进行有针对性的分析； 炎性脂质介质(13种代谢物)检查对空气变化的代谢反应 三个研究期间的污染水平，以及(2)使用高水平的 吞吐量方法(886种代谢物)，以发现对剧烈变化反应强烈的代谢物 空气污染水平，以及确定新的途径和代谢特征，代表总体 代谢变化。 我们已经进行了一项试验研究，以探讨拟议项目的可行性。我们观察到很明显 多种途径的变化，包括脂肪酸、过氧化脂质和二十烷类化合物，这与 在我们的父母研究中，谷胱甘肽过氧化物酶(GPX)活性是由空气诱导的 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 研究人类暴露在空气污染中，揭示脂质过氧化和炎性脂质的关键作用 中介，并为未来的研究产生关于相关路径的新假设。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 曝光。我们预计这些发现将在未来的研究中与临床结果联系起来。

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.