邻苯二甲酸酯暴露的人群代谢组学研究
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摘要
邻苯二甲酸酯是一类典型的内分泌干扰物,在各国人群的尿液样本中均能检测到其代谢物-单酯的存在,表明各国人群均普遍暴露于邻苯二甲酸酯。邻苯二甲酸酯暴露与人群代谢组之间的关联性研究还鲜有报道。本研究中,我们收集了364份正常男性的尿液,测定了邻苯二甲酸酯的内暴露水平,采集了尿液的代谢指纹图谱,利用化学计量学方法对样本进行聚类分析,并筛选暴露效应标志物,用于未来的健康风险评估。代谢组学分析(图1)表明,DEHP和DBP暴露确实会对代谢系统产生显著的影响,低暴露和高暴露人群的样本均可聚类在各自的区域。我们筛选鉴定了暴露效应标志物,包括若干酰基肉碱、氨基酸及衍生物、前列腺素等等。DEHP和DBP暴露具有相似的暴露效应暴露物以及变化趋势。在此基础上,我们进一步通过标志物组合建立了健康效应评估模型。组合可以对不同暴露程度的样本进行准确的区分,在未来的人群风险评估中具有一定的应用潜力。
The ubiquitousness of phthalates results in widespread exposure to these chemicals among the general population.The integration of omics data with mechanistic and epidemiological data is a key step towards the goal of linking biomarkers of exposure and susceptibility to disease mechanisms and outcomes.In this study,for the first time we conducted urine metabolomics study involving a cohort of 364 Chinese men.Urine metabolic profiles could bedifferentiated according to internal exposure level of phthalates.Sixteen potential biomarkers changed in a dose-dependent manner.The types of metabolic biomarkers of DEHP and DBP exposure are similar,but not identical.The identified biomarkers also showed similar trend change in both DBP and DEHP models,indicating these two phthalates may exert similar disruption effect on metabolism network.The multi-biomarker models(top ten biomarker combination) presented AUC values 0.834 and 0.845 for DBP and DEHP,respectively.Pathway analysis showed ambient phthalate exposure may increase fatty acid oxidation,inhibit prostaglandin pathways and disrupt amino acid metabolism in humans.
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