Low-Level Environmental Phthalate Exposure Associates with Urine Metabolome Alteration in a Chinese Male Cohort.
Low-Level Environmental Phthalate Exposure Associates with Urine Metabolome Alteration in a Chinese Male Cohort.
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DOI：
10.1021/acs.est.6b00034
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发表时间：
2016-05
影响因子：
11.4
通讯作者：
Jie Zhang;Liangpo Liu;Xiaofei Wang;Qingyu Huang;Meiping Tian;Heqing Shen
中科院分区：
文献类型：
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作者：
Jie Zhang;Liangpo Liu;Xiaofei Wang;Qingyu Huang;Meiping Tian;Heqing Shen
一般人群通过各种来源和途径接触邻苯二甲酸盐。组学数据和流行病学数据的整合是将邻苯二甲酸盐生物监测数据与生物反应直接联系起来的关键一步。尿液代谢组学是识别暴露生物标志物和描述环境压力源作用模式的强大工具。本研究的目的是调查低水平环境邻苯二甲酸盐暴露与男性人群尿液代谢组改变之间的关联，并揭示邻苯二甲酸盐毒性机制所涉及的代谢途径。在这项回顾性横断面研究中，我们研究了 364 名暴露于低浓度环境邻苯二甲酸盐的男性受试者的尿液代谢组学特征。邻苯二甲酸二(2-乙基己基)酯 (DEHP) 和邻苯二甲酸二丁酯 (DBP) 是最广泛使用的邻苯二甲酸酯。 ΣDEHP 和 MBP（DBP 的主要代谢物）与男性人群整体尿液代谢组的显着改变相关。我们观察到乙酰神经氨酸、肉碱 C8:1、肉碱 C18:0、胱氨酸、苯甘氨酸、苯丙酮酸和谷氨酰苯丙氨酸的水平显着增加；同时，高暴露组肉毒碱C16:2、二乙酰精胺、丙氨酸、牛磺酸、色氨酸、鸟氨酸、甲基戊二酸、羟基-PEG2和酮-PGE2水平下降。观察结果表明，低水平的环境邻苯二甲酸盐暴露与氧化应激和脂肪酸氧化增加以及前列腺素代谢减少相关。还观察到尿素循环、色氨酸和苯丙氨酸代谢破坏。 ΣDEHP 和 MBP 相关的尿液代谢组破坏效应相似，但不相同。多生物标志物模型显示 ΣDEHP 和 MBP 的 AUC 值分别为 0.845 和 0.834。建立的模型的预测准确率：ΣDEHP 为 81%，MBP 为 73%。我们的研究结果表明，低水平的环境邻苯二甲酸盐暴露与男性人群的尿液代谢组破坏相关，这为了解邻苯二甲酸盐暴露的早期分子事件提供了新的见解。
The general population is exposed to phthalates through various sources and routes. Integration of omics data and epidemiological data is a key step toward directly linking phthalate biomonitoring data with biological response. Urine metabolomics is a powerful tool to identify exposure biomarkers and delineate the modes of action of environmental stressors. The objectives of this study are to investigate the association between low-level environmental phthalate exposure and urine metabolome alteration in male population, and to unveil the metabolic pathways involved in the mechanisms of phthalate toxicity. In this retrospective cross-sectional study, we studied the urine metabolomic profiles of 364 male subjects exposed to low-level environmental phthalates. Di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) are the most widely used phthalates. ∑DEHP and MBP (the major metabolite of DBP) were associated with significant alteration of global urine metabolome in the male population. We observed significant increase in the levels of acetylneuraminic acid, carnitine C8:1, carnitine C18:0, cystine, phenylglycine, phenylpyruvic acid and glutamylphenylalanine; and meanwhile, decrease in the levels of carnitine C16:2, diacetylspermine, alanine, taurine, tryptophan, ornithine, methylglutaconic acid, hydroxyl-PEG2 and keto-PGE2 in high exposure group. The observations indicated that low-level environmental phthalate exposure associated with increased oxidative stress and fatty acid oxidation and decreased prostaglandin metabolism. Urea cycle, tryptophan and phenylalanine metabolism disruption was also observed. The urine metabolome disruption effects associated with ∑DEHP and MBP were similar, but not identical. The multibiomarker models presented AUC values of 0.845 and 0.834 for ∑DEHP and MBP, respectively. The predictive accuracy rates of established models were 81% for ΣDEHP and 73% for MBP. Our results suggest that low-level environmental phthalate exposure associates with urine metabolome disruption in male population, providing new insight into the early molecular events of phthalate exposure.