Aristotle University of Thessaloniki, Department of Chemical Engineering, Environmental Engineering Laboratory, University Campus, Thessaloniki, 54124, Greece; HERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Balkan Center, Bldg. B, 10thkm Thessaloniki-Thermi Road, 57001, Greece; School for Advanced Study (IUSS), Science, Technology and Society Department, Environmental Health Engineering, Piazza Della Vittoria 15, Pavia, 27100, Italy.
Aristotle University of Thessaloniki, Department of Chemical Engineering, Environmental Engineering Laboratory, University Campus, Thessaloniki, 54124, Greece; HERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Balkan Center, Bldg. B, 10thkm Thessaloniki-Thermi Road, 57001, Greece.
Environ Res. 2021 Jun;197:110949. doi: 10.1016/j.envres.2021.110949. Epub 2021 Mar 11.
In this study, the exposome paradigm has been applied on a mother-child cohort adopting an optimised untargeted metabolomics approach for human urine followed by advanced bioinformatics analysis. Exposome-wide association algorithms were used to draw links between in utero co-exposure to metals and phthalates, metabolic pathways deregulation, and clinically observed phenotypes of neurodevelopmental disorders such as problems in linguistic, motor development and cognitive capacity. Children (n = 148) were tested at the first and second year of their life using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Their mothers had been exposed to metals and phthalates during the pregnancy, according to human biomonitoring results from previously performed studies. Untargeted metabolomics analysis of biobanked urine samples from the mothers was performed using a combination of the high throughput analytical methods liquid chromatography-high resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR). Most perturbed metabolic pathways from co-exposure heavy metals and phthalates were pathways related to the tricarboxylic acid cycle (TCA cycle) and oxidative phosphorylation, indicating the possibility of disruption of mitochondrial respiration. Overproduction of reactive oxygen species (ROS); the presence of glutathione peroxidase 3 (GPx3) during pregnancy and presence of glutathione peroxidase 1 (GPx1) in the umbilical cord were linked to verbal development problems. Another finding of the study is that in real life, adverse outcomes occur as a combination of environmental and social factors, all of them acting synergistically towards the deployment of an observed phenotype. Finally, the two-steps association process (exposure to pathways and pathways to adverse outcomes) was able to (a) provide associations that are not evident by directly associating exposure to outcomes and (b) provides additional insides on the mechanisms of environmental disease.
在这项研究中，采用了一种优化的非靶向代谢组学方法对人类尿液进行检测，并结合先进的生物信息学分析，应用暴露组学范式对母子队列进行研究。采用暴露组关联算法，将子宫内共同暴露于金属和邻苯二甲酸酯、代谢途径失调，以及临床上观察到的神经发育障碍表型（如语言、运动发育和认知能力问题）之间建立联系。对 148 名儿童在他们生命的第一年和第二年使用贝利婴幼儿发育量表第三版（Bayley-III）进行测试。根据之前进行的研究中人类生物监测的结果，他们的母亲在怀孕期间暴露于金属和邻苯二甲酸酯中。对母亲的生物银行尿液样本进行非靶向代谢组学分析，采用液相色谱-高分辨质谱（LC-HRMS）和核磁共振（NMR）高通量分析方法相结合。共同暴露于重金属和邻苯二甲酸酯后最受干扰的代谢途径是与三羧酸循环（TCA 循环）和氧化磷酸化相关的途径，这表明线粒体呼吸可能受到干扰。活性氧（ROS）的过度产生；怀孕期间存在谷胱甘肽过氧化物酶 3（GPx3），脐带中存在谷胱甘肽过氧化物酶 1（GPx1）与语言发育问题有关。该研究的另一个发现是，在现实生活中，不良后果是环境和社会因素共同作用的结果，所有这些因素都协同作用于观察到的表型的出现。最后，两步关联过程（暴露于途径和途径至不良后果）能够（a）提供直接将暴露与结果相关联所不明显的关联，（b）提供环境疾病机制的额外见解。
