Environmental factors, such as environmental pollutants, behaviors, and lifestyles, are the leading causes of chronic noncommunicable diseases. Estimates indicate that approximately 50% of all deaths worldwide can be attributed to environmental factors. The exposome is defined as the totality of human environmental (i.e., all nongenetic) exposures from conception, including general external exposure (e.g., climate, education, and urban environment), specific external exposure (e.g., pollution, physical activity, and diet), and internal exposure (e.g., metabolic factors, oxidative stress, inflammation, and protein modification). As a new paradigm, this concept aims to comprehensively understand the link between human health and environmental factors. Therefore, a comprehensive measurement of the exposome, including accurate and reliable measurements of exposure to the external environment and a wide range of biological responses to the internal environment, is of great significance. The measurement of the general external exposome depends on advances in environmental sensors, personal-sensing technologies, and geographical information systems. The determination of exogenous chemicals to which individuals are exposed and endogenous chemicals that are produced or modified by external stressors relies on improvements in methodology and the development of instrumental approaches, including colorimetric, chromatographic, spectral, and mass-spectrometric methods. This article reviews the research strategies for chemical exposomes and summarizes existing exposome-measurement methods, focusing on mass spectrometry (MS)-based methods. The top-down and bottom-up approaches are commonly used in exposome studies. The bottom-up approach focuses on the identification of chemicals in the external environment (e.g., soil, water, diet, and air), whereas the top-down approach focuses on the evaluation of endogenous chemicals and biological processes in biological samples (e.g., blood, urine, and serum). Low- and high-resolution MS (LRMS and HRMS, respectively) have become the most popular methods for the direct measurement of exogenous and endogenous chemicals owing to their superior sensitivity, specificity, and dynamic range. LRMS has been widely applied in the targeted analysis of expected chemicals, whereas HRMS is a promising technique for the suspect and unknown screening of unexpected chemicals. The development of MS-based multiomics, including proteomics, metabolomics, epigenomics, and spatial omics, provides new opportunities to understand the effects of environmental exposure on human health. Metabolomics involves the sum of all low-molecular-weight metabolites in a living system. Nontargeted metabolomics can measure both endogenous and exogenous chemicals, which would directly link exposure to biological effects, internal dose, and disease pathobiology, whereas proteomics could play an important role in predicting potential adverse health outcomes and uncovering molecular mechanisms. MS imaging (MSI) is an emerging technique that provides unlabeled in-depth measurements of endogenous and exogenous molecules directly from tissue and cell sections without changing their spatial information. MSI-based spatial omics, which has been widely applied in biomarker discovery for clinical diagnosis, as well as drug and pollutant monitoring, is expected to become an effective method for exposome measurement. Integrating these response measurements from metabolomics, proteomics, spatial omics, and epigenomics will enable the generation of new hypotheses to discover the etiology of diseases caused by chemical exposure. Finally, we highlight the major challenges in achieving chemical exposome measurements.
暴露组定义为从受孕开始人类环境(即所有非遗传)暴露的总和,旨在全面了解人类健康与环境化学品暴露之间的关联。因此,对暴露组的全面测量至关重要,包括准确可靠地测量外部环境中的暴露及内部环境中的生物反应。化学暴露组既包括个体受外源性化学物质暴露的总和(外暴露),也包括因外部压力而产生或改变的内源性化学物质暴露的总和(内暴露)。随着新一代高通量、高分辨质谱技术的发展,以质谱分析驱动的多组学研究技术将为暴露组内、外源污染物的鉴定分析带来新的范式。本文主要综述了化学暴露组学的研究策略及现有的化学暴露测量方法,重点介绍了代谢组学、蛋白质组学以及基于质谱成像的空间组学技术在化学暴露组研究中的应用现状及未来发展前景。当前,质谱技术因其灵敏度高、特异性强和动态范围宽的优势已成为检测外暴露的主要方法,基于低分辨质谱的针对性分析以及基于高分辨质谱的可疑筛查和未知筛查技术已广泛应用于测量人类对各种化学品的暴露。此外,代谢组学、蛋白质组学和基于质谱成像的空间组学技术作为内暴露的有效检测方法,在预测潜在的不良健康结果和揭示内在分子机制中发挥了重要的作用。同时我们讨论了本课题组在化学暴露组学领域所取得的研究进展,并提出了实现化学暴露组测量所面临的主要挑战。
Keywords: expotomics; mass spectrometry (MS); mass spectrometry imaging (MSI); metabolomics; proteomics; review.