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Characterization of the human exposome by a comprehensive and quantitative large scale multi-analyte metabolomics platform.
Analytical Chemistry ( IF 6.7 ) Pub Date : 2020-09-23 , DOI: 10.1021/acs.analchem.0c02008
Raúl González-Domínguez 1, 2 , Olga Jáuregui 2, 3 , María Isabel Queipo-Ortuño 4, 5 , Cristina Andrés-Lacueva 1, 2
Affiliation  

The exposome, defined as the cumulative measure of external exposures and associated biological responses throughout the lifespan, has emerged in recent years as a cornerstone in biomedical sciences. Metabolomics stands out here as one of the most powerful tools for investigating the interplay between the genetic background, exogenous, and endogenous factors within human health. However, to address the complexity of the exposome, novel methods are needed to characterize the human metabolome. In this work, we have optimized and validated a multianalyte metabolomics platform for large-scale quantitative exposome research in plasma and urine samples, based on the use of simple extraction methods and high-throughput metabolomic fingerprinting. The methodology enables, for the first time, the simultaneous characterization of the endogenous metabolome, food-related metabolites, pharmaceuticals, household chemicals, environmental pollutants, and microbiota derivatives, comprising more than 1000 metabolites in total. This comprehensive and quantitative investigation of the exposome is achieved in short run times, through simple extraction methods requiring small-sample volumes, and using integrated quality control procedures for ensuring data quality. This metabolomics approach was satisfactorily validated in terms of linearity, recovery, matrix effects, specificity, limits of quantification, intraday and interday precision, and carryover. Furthermore, the clinical potential of the methodology was demonstrated in a dietary intervention trial as a case study. In summary, this study describes the optimization, validation, and application of a multimetabolite platform for comprehensive and quantitative metabolomics-based exposome research with great utility in large-scale epidemiological studies.

中文翻译:

通过全面,定量的大规模多分析物代谢组学平台表征人类暴露小体。

近年来,暴露体已被定义为生物医学科学的基石,暴露体是在整个生命周期中对外部暴露和相关生物反应的累积量度。在这里,代谢组学是研究人类健康中遗传背景,外源性和内源性因素之间相互作用的最强大工具之一。然而,为了解决暴露体的复杂性,需要新颖的方法来表征人类代谢组。在这项工作中,我们已经基于简单的提取方法和高通量代谢组学指纹图谱的使用,优化并验证了用于血浆和尿液样品大规模定量暴露研究的多分析物代谢组学平台。该方法首次实现了内源性代谢组的同时表征,与食物有关的代谢产物,药物,日用化学品,环境污染物和微生物群衍生物,总共包含1000多种代谢产物。通过简单的提取方法(需要少量样品)以及使用集成的质量控制程序来确保数据质量,可以在较短的运行时间内对暴露体进行全面而定量的研究。该代谢组学方法在线性,回收率,基质效应,特异性,定量限,日内和日间精度以及结转方面均得到了令人满意的验证。此外,该方法的临床潜力在饮食干预试验中得到了证实。总之,本研究描述了优化,验证,
更新日期:2020-10-21
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