暴露组学的概念与应用

暴露组学作为基因组学的补充是指从妊娠开始贯穿整个人生的环境暴露(包括生活方式因素)。暴露源包括外源(污染、辐射、饮食等)和内源(炎症、感染、微生物等)。继全基因组关联研究(GWAS)之后发展的全暴露组关联研究(EWAS)的目的是对在未知方式下暴露的评估。EWAS方法通过比较患者和健康受试者暴露组的分析结果,确定有效的生物标志物,进而利用这些生物标志物来阐明暴露-效应关系(生化流行病学)、暴露和人体动力学来源(暴露生物学),以及作用机制(系统生物学)。"自下而上"和"自上而下"的方法在识别个体暴露上都具有科学价值。"自上而下"法用于揭示人类疾病的未知暴露源,而"自下而上"法是用于分析外暴露以及建立干预与预防的方法。生物标志物不仅可以用于研究外暴露,也可以用于研究内暴露。内暴露组学采用组学的方法进行研究,如基因组学、蛋白质组学、表观基因组学、代谢组学、转录组学、加合物组学等。人类生命早期暴露组学(HELIX)项目是近期启动的描述欧洲人群的早期暴露以及揭示组学标志物和儿童时期健康关系的第一次尝试。该文介绍了其研究方法、工具、思路及其重要意义,同时总结了暴露组学从概念到应用可能面临的挑战。     

基于多组学的肿瘤病因学研究：从基因组学、暴露组学、代谢组学到系统流行病学

探索疾病病因是流行病学的主要任务之一。随着基因组、转录组、蛋白质组、代谢组、暴露组等组学技术的进步, 肿瘤病因学研究进入系统流行病学研究阶段。基因组学研究致力于发掘肿瘤遗传易感位点及其致病机制。暴露组学研究探索环境因素对机体生物学过程的影响及其致病效应。而代谢组处于生物调控网络的下游, 反映了基因-环境及其交互作用的总效应, 有助于阐明遗传和环境因素的致病机制, 发现新的生物标志物。本文介绍基因组学、暴露组学和代谢组学在肿瘤病因学研究中的应用与进展, 总结多组学和系统流行病学在肿瘤病因学研究中的意义和价值, 展望未来发展方向。     

代谢组学在心血管代谢疾病病因研究中的应用进展

代谢组学是采用高通量组学技术对所有代谢物进行鉴定和定量的生命科学研究, 近年来在心血管代谢疾病的病因研究中得到广泛应用。作为系统流行病学的一个重要组成部分, 代谢组学从代谢改变的视角提供了病因探索的新思路。代谢组学的研究问题包括分析代谢物与心血管代谢疾病的关联、发现新型生物标志物和构建疾病风险预测模型等。本文从物质类别出发详细介绍代谢组学在2型糖尿病、心血管疾病、高血压和亚临床动脉粥样硬化病因研究中的应用进展, 并提出展望。     

代谢组流行病学研究进展

近年来，基于代谢组学技术平台和数据分析方法的快速发展，作为系统流行病学的重要分支——代谢组流行病学正获得越来越多的关注。代谢组流行病学有助于更好地描述暴露特征，反映环境-基因相互作用的效应，阐明暴露与疾病的"黑箱"机制，并发现新的生物标志物。本文简要介绍代谢组流行病学研究的定义、方法、研究进展及展望。     

空气污染暴露测量技术的现状及发展趋势

目的空气污染物暴露测量技术的选择关系到空气污染健康影响研究结果的准确性。精细化的暴露测量方法对于提高研究结果的可靠性和准确性具有重要意义。随着当前空间信息、遥感、分析测试等技术的发展,趋于高时空分辨率、个体化监测以及基于暴露学和代谢组学的精细化暴露测量技术逐渐发展起来,并被应用到大气污染健康影响研究中。该文从人群环境暴露、个体暴露和生物标志物三方面介绍了空气污染健康影响研究中暴露测量技术的现状及发展趋势。     

人类生命早期暴露组(HELIX):项目理念与设计(待续)

[背景]人类在生命早期的发育期间可能特别容易受到环境暴露的影响。有关这一主题的人体研究一般集中在单一暴露与健康效应之间的关系。而"暴露组"的概念涵盖了从受孕开始的的全部暴露,完善了基因组。[目的]人类生命早期暴露组(HELIX)项目是一个新的合作研究项目,目的是为了采用新的暴露评估和生物标志分析方法来描述生命早期多种环境因素的暴露,并将这些与生物标志组学和儿童健康结局相关联,从而刻画"生命早期暴露组"。本文描述了该项目的总体设计。[方法]HELIX将利用欧洲现有的6个出生队列研究来估计产前、产后暴露的一系列化学和物理暴露。建立全部队列中总共32 000对母亲和儿童的暴露模型,并在一个包含1 200对母亲和儿童的子队列中测量生物标志。嵌套重复采样的定组研究(n=150)将收集生物标志的变化数据,利用智能手机来评估流动性和体力活动,并监测个体暴露。采用组学技术确定与暴露相关的分子学特征(代谢组、蛋白质组、转录组和表观基因组)。对于多次暴露,采用统计方法估计胎儿和儿童的成长、肥胖、神经发育和呼吸系统结局中的暴露-效应关系。项目还将进行一项健康效应评估测试,以评价组合暴露的风险和收益。[结论]HELIX是描述欧洲人群生命早期暴露组并解开它与组学标志物和儿童健康之间关联的首次尝试之一。作为对暴露组学这一概念的验证,该项目向生命过程中暴露组迈出了重要的第一步。     

《生物监测与生物标志物理论基础及应用》新书预告

由沈惠麒教授、顾祖维研究员、吴宜群研究员为主编,郑玉新研究员和贾光教授为副主编的《生物监测与生物标志物理论基础及应用》一书,近日由北京大学医学出版社再版发行,全书定价49．80元。本书系统介绍了生物监测与生物标志物的基本概念和应用,结合国内外本领域最新研究进展,重点介绍了生物监测与生物标志物在常见有毒、有害因素研究中的应用及规     

评价食品中致癌物作用的生物学标志物

膳食因素与人类癌症密切相关。对膳食中致癌物作用的危险性评估需要考虑人群暴露水平、生物效应和个体易感性 ,而发展特异的生物标志物对正确评估机体暴露水平和探讨生物效应和个体易感性具有重要意义。生物标志物包括暴露标志物、效应标志物和易感性标志物。暴露生物标志物又包括体内剂量生物标志物和有效剂量生物标志物。本文拟就膳食中重要致癌物的危险性评估中的潜在生物标志物研究进展进行综述。     

多环芳烃暴露生物标志物羟基多环芳烃检测方法的研究进展

多环芳烃(PAHs)是一类普遍存在于环境中的持久性有机污染物,长期暴露可引发肺癌、皮肤癌等恶性肿瘤。而PAHs的代谢物——单羟基多环芳烃(OH-PAHs)可以作为暴露生物标志物综合评价人体对PAHs的暴露水平,从而吸引众多研究人员对OH-PAHs检测方法的研究。笔者介绍了生物标志物以及选用OH-PAHs作为生物标志物的意义,系统综述了OH-PAHs的各种检测方法,包括高效液相色谱法、液相色谱-质谱(气相色谱-质谱)联用技术、同步荧光光谱分析法、毛细管区带电泳法、酶联免疫法和电化学法,并对其检测方法的发展趋势进行了评价和展望。     

《工业卫生与职业病》第四届编辑委员会委员名单

由沈惠麒教授（北京大学）、顾祖维研究员（上海疾病预防控制中心）、吴宜群研究员（中国疾病预防控制中心）为主编，郑玉新研究员（中国疾病预防控制中心）和贾光教授（北京大学）为副主编的《生物监测与生物标志物理论基础及应用》一书，近日由北京大学医学出版社再版发行，全书定价49．80元。本书系统介绍了生物监测与生物标志物的基本概念和应用，结合国内外本领域最新研究进展，重点介绍了生物监测与生物标志物在常见有毒、有害因素研究中的应用及规范化的研究方法。     

环境污染暴露评估的研究进展

环境污染暴露评估研究是环境健康研究的重要组成部分,充分分析环境污染物暴露的研究前沿对把握环境污染暴露研究的发展方向及准确评价健康风险具有重要作用。该文从环境污染的外暴露、内暴露、复合暴露及暴露组学几个方面入手,充分分析区域尺度暴露评估模型、大范围生物连续监测、内分泌干扰物内暴露水平、污染内暴露技术及复合暴露和暴露组学等前沿问题的国内外研究现状,最后对我国环境污染暴露评估的研究方向进行了展望。     

Adopting a “Compound” Exposome Approach in Environmental Aging Biomarker Research: A Call to Action for Advancing Racial Health Equity

Background: In June 2020, the National Academies of Sciences, Engineering, and Medicine hosted a virtual workshop focused on integrating the science of aging and environmental health research. The concurrent COVID-19 pandemic and national attention on racism exposed shortcomings in the environmental research field’s conceptualization and methodological use of race, which have subsequently hindered the ability of research to address racial health disparities. By the workshop’s conclusion, the authors deduced that the utility of environmental aging biomarkers—aging biomarkers shown to be specifically influenced by environmental exposures—would be greatly diminished if these biomarkers are developed absent of considerations of broader societal factors—like structural racism—that impinge on racial health equity.Objectives: The authors reached a post-workshop consensus recommendation: To advance racial health equity, a “compound” exposome approach should be widely adopted in environmental aging biomarker research. We present this recommendation here.Discussion: The authors believe that without explicit considerations of racial health equity, people in most need of the benefits afforded by a better understanding of the relationships between exposures and aging will be the least likely to receive them because biomarkers may not encompass cumulative impacts from their unique social and environmental stressors. Employing an exposome approach that allows for more comprehensive exposure–disease pathway characterization across broad domains, including the social exposome and neighborhood factors, is the first step. Exposome-centered study designs must then be supported with efforts aimed at increasing the recruitment and retention of racially diverse study populations and researchers and further “compounded” with strategies directed at improving the use and interpretation of race throughout the publication and dissemination process. This compound exposome approach maximizes the ability of our science to identify environmental aging biomarkers that explicate racial disparities in health and best positions the environmental research community to contribute to the elimination of racial health disparities. https://doi.org/10.1289/EHP8392     

Discovering environmental causes of disease

Although chronic diseases are primarily environmental (ie, not genetic) in origin, the particular environmental causes of these diseases are poorly understood. A WHO study of worldwide cancer mortality identified nine diverse environmental factors, including pollution, diet, lifestyle factors and infections. However, the joint effect of these nine factors accounted for only about one-third of cancer mortality, indicating that about two-thirds are of unknown aetiology. One problem relates to the community of epidemiologists, which sorts environmental factors into marginally overlapping domains, thereby creating gaps in coverage. Also, information about environmental exposures in epidemiologic studies is generally derived from questionnaires that are ill suited for assessing thousands of potentially causative exposures. Finally, the few studies that rigorously estimate exposure levels focus upon a handful of pollutants of regulatory importance and thus are unsuited for finding hitherto unrecognised exposures from both exogenous and endogenous sources. The concept of the 'exposome'-representing the totality of exposures from gestation onwards-has recently been introduced as a complement to the genome in studies of disease aetiology. The exposome concept promotes environmental analogues of genome-wide association studies, which employ untargeted omic methods to compare biospecimens from diseased and healthy subjects. The goal of such investigations is to discover key biomarkers of exposure that enable follow-up hypotheses to be explored regarding sources of exposure, dose-response relationships, mechanisms of action, disease causality and public health interventions. Examples of this approach are cited from recent metabolomic studies of several complex chronic diseases.     

Understanding the link between environmental exposures and health: does the exposome promise too much?

Environmental exposures affecting human health range from complex mixtures, such as environmental tobacco smoke, ambient particulate matter air pollution and chlorination by products in drinking water, to hazardous chemicals, such as lead, and polycyclic aromatic hydrocarbons, such as benz(a)pyrene. The exposome has been proposed to complement the genome and be the totality of all environmental exposures of an individual over his or her lifetime. However, if measurements of the exposome in biological samples are the sole tool for exposure assessment there are a number of limitations. First, it has limited utility for fully capturing the impact of complex mixtures such environmental tobacco smoke or particulate matter air pollution. Second, a number of relevant environmental exposures such as noise, heat or electromagnetic fields do not have direct correlates as metabolites or protein adducts, but there is important evidence linking them with health effects. Third, functional genomic changes are likely in many instances to be both a susceptibility factor and a marker of internal doses in response to environmental exposures. Fourth, internal dose measurements of environmental exposures might have lost the distinct signature of the relevant sources. This paper emphasises the obligation of environmental epidemiology to provide robust evidence to assist timely and sufficient protection of vulnerable subgroups of populations from environmental hazards. Therefore, in applying the exposome concept to environmental health problems, a strong link with the external environment needs to be maintained.     

Towards a toxic-free environment: perspectives for chemical risk assessment approaches.

Regulatory frameworks to control chemical exposure in general living and occupational environments have changed exposure scenarios towards a widely spread contamination at relatively low doses in developed countries. In such evolving context, some critical aspects should be considered to update risk assessment and management strategies. Risk assessment in low-dose chemical exposure scenarios should take advantage of: toxicological investigations on emerging substances of interest, like those recognised as endocrine disruptors or increasingly employed nanoscale materials; human biological monitoring studies aimed to identify innovative biomarkers for known chemical exposure; “omic” technologies useful to identify hazards of chemicals and their modes of action. For updated risk assessment models, suitable toxicological studies, analyses of dose-responses at low-concentrations, environmental and biological monitoring of exposure, together with exposome studies, and the proper definition of susceptible populations may all provide helpful contributions. These may guide defining preventive measures to control the exposure and develop safe and sustainable chemicals by design. Occupational medicine can offer know-how and instruments to understand and manage such evolution towards a toxic-free environment to protect the safety and health of the workforce and, in turn, that of the general population.     

MicroRNAs as Potential Signatures of Environmental Exposure or Effect: A Systematic Review

Background: The exposome encompasses all life-course environmental exposures from the prenatal period onward that influence health. MicroRNAs (miRNAs) are interesting entities within this concept as markers and causation of disease. MicroRNAs are short oligonucleotide sequences that can interact with several mRNA targets.Objectives: We reviewed the current state of the field on the potential of using miRNAs as biomarkers for environmental exposure. We investigated miRNA signatures in response to all types of environmental exposure to which a human can be exposed, including cigarette smoke, air pollution, nanoparticles, and diverse chemicals; and we examined the health conditions for which the identified miRNAs have been reported (i.e., cardiovascular disease, cancer, and diabetes).Methods: We searched the PubMed and ScienceDirect databases to identify relevant studies.Results: For all exposures incorporated in this review, 27 miRNAs were differentially expressed in at least two independent studies. miRNAs that had expression alterations associated with smoking observed in multiple studies are miR-21, miR-34b, miR-125b, miR-146a, miR-223, and miR-340; and those miRNAs that were observed in multiple air pollution studies are miR-9, miR-10b, miR-21, miR-128, miR-143, miR-155, miR-222, miR-223, and miR-338. We found little overlap among in vitro, in vivo, and human studies between miRNAs and exposure. Here, we report on disease associations for those miRNAs identified in multiple studies on exposure.Conclusions: miRNA changes may be sensitive indicators of the effects of acute and chronic environmental exposure. Therefore, miRNAs are valuable novel biomarkers for exposure. Further studies should elucidate the role of the mediation effect of miRNA between exposures and effect through all stages of life to provide a more accurate assessment of the consequences of miRNA changes.Citation: Vrijens K, Bollati V, Nawrot TS. 2015. MicroRNAs as potential signatures of environmental exposure or effect: a systematic review. Environ Health Perspect 123:399–411; http://dx.doi.org/10.1289/ehp.1408459     

Biomarkers of immunotoxicity for environmental and public health research

The immune response plays an important role in the pathophysiology of numerous diseases including asthma, autoimmunity and cancer. Application of biomarkers of immunotoxicity in epidemiology studies and human clinical trials can improve our understanding of the mechanisms that underlie the associations between environmental exposures and development of these immune-mediated diseases. Immunological biomarkers currently used in environmental health studies include detection of key components of innate and adaptive immunity (e.g., complement, immunoglobulin and cell subsets) as well as functional responses and activation of key immune cells. The use of high-throughput assays, including flow cytometry, Luminex, and Multi-spot cytokine detection methods can further provide quantitative analysis of immune effects. Due to the complexity and redundancy of the immune response, an integrated assessment of several components of the immune responses is needed. The rapidly expanding field of immunoinformatics will also aid in the synthesis of the vast amount of data being generated. This review discusses and provides examples of how the identification and development of immunological biomarkers for use in studies of environmental exposures and immune-mediated disorders can be achieved.     

Implications of the exposome for exposure science

During the 1920s, the forerunners of exposure science collaborated with health professionals to investigate the causes of occupational diseases. With the birth of U.S. regulatory agencies in the 1970s, interest in the environmental origins of human diseases waned, and exposure scientists focused instead upon levels of selected contaminants in air and water. In fact, toxic chemicals enter the body not only from exogenous sources (air, water, diet, drugs, and radiation) but also from endogenous processes, including inflammation, lipid peroxidation, oxidative stress, existing diseases, infections, and gut flora. Thus, even though current evidence suggests that non-genetic factors contribute about 90% of the risks of chronic diseases, we have not explored the vast majority of human exposures that might initiate disease processes. The concept of the exposome, representing the totality of exposures received by a person during life, encompasses all sources of toxicants and, therefore, offers scientists an agnostic approach for investigating the environmental causes of chronic diseases. In this context, it is appropriate to regard the "environment" as the body's internal chemical environment and to define "exposures" as levels of biologically active chemicals in this internal environment. To explore the exposome, it makes sense to employ a top-down approach based upon biomonitoring (e.g. blood sampling) rather than a bottom-up approach that samples air, water, food, and so on. Because sources and levels of exposure change over time, exposomes can be constructed by analyzing toxicants in blood specimens obtained during critical stages of life. Initial investigations could use archived blood from prospective cohort studies to measure important classes of toxic chemicals, notably, reactive electrophiles, metals, metabolic products, hormone-like substances, and persistent organic compounds. The exposome offers health scientists an avenue for integrating research that is currently fractured along lines related to particular diseases and risk factors, and can thereby promote discovery of the key exposures responsible for chronic diseases. By embracing the exposome as its operational paradigm, exposure science can play a major role in discovering and mitigating these exposures.     

The Exposome and Immune Health in Times of the COVID-19 Pandemic

Growing evidence supports the importance of lifestyle and environmental exposures—collectively referred to as the ‘exposome’—for ensuring immune health. In this narrative review, we summarize and discuss the effects of the different exposome components (physical activity, body weight management, diet, sun exposure, stress, sleep and circadian rhythms, pollution, smoking, and gut microbiome) on immune function and inflammation, particularly in the context of the current coronavirus disease 2019 (COVID-19) pandemic. We highlight the potential role of ‘exposome improvements’ in the prevention—or amelioration, once established—of this disease as well as their effect on the response to vaccination. In light of the existing evidence, the promotion of a healthy exposome should be a cornerstone in the prevention and management of the COVID-19 pandemic and other eventual pandemics.