Humans are exposed to an ever-increasing number of environmental toxicants, some of which have gradually been elucidated to be important risk factors for metabolic diseases, such as diabetes and obesity. These metabolism-sensitive diseases typically occur when key metabolic and signaling pathways were disrupted, which can be influenced by the exposure to contaminants such as endocrine disrupting chemicals (EDCs), along with genetic and lifestyle factors. This promotes the concept and research on environmental metabolism disrupting chemicals (MDCs). In addition, identifying endogenous biochemical markers of effect linked to disease states is becoming an important tool to screen the biological targets following environmental contaminant exposure, as well as to provide an overview of toxicity risk assessment. As such, the current review aims to contribute to the further understanding of exposome and human health and disease by characterizing environmental exposure and effect metabolic biomarkers. We summarized MDC-associated metabolic biomarkers in laboratory animal and human cohort studies using high throughput targeted and nontargeted metabolomics techniques. Contaminants including heavy metals and organohalogen compounds, especially EDCs, have been repetitively associated with metabolic disorders, whereas emerging contaminants such as perfluoroalkyl substances and microplastics have also been found to disrupt metabolism. In addition, we found major limitations in the effective identification of metabolic biomarkers especially in human studies, toxicological research on the mixed effect of environmental exposure has also been insufficient compared to the research on single chemicals. Thus, it is timely to call for research efforts dedicated to the study of combined effect and metabolic alterations for the better assessment of exposomic toxicology and health risks. Moreover, advanced computational and prediction tools, further validation of metabolic biomarkers, as well as systematic and integrative investigations are also needed in order to reliably identify novel biomarkers and elucidate toxicity mechanisms, and to further utilize exposome and metabolome profiling in public health and safety management.

人类暴露于越来越多的环境毒物中，其中一些已逐渐被阐明为糖尿病和肥胖等代谢疾病的重要危险因素。这些代谢敏感疾病通常发生在关键的代谢和信号通路被破坏时，这可能会受到诸如内分泌干扰化学物质 (EDC) 等污染物的影响，以及遗传和生活方式因素的影响。这促进了环境代谢破坏化学品（MDCs）的概念和研究。此外，识别与疾病状态相关的内源性生化标志物正在成为筛选环境污染物暴露后的生物靶标以及提供毒性风险评估概述的重要工具。像这样，目前的审查旨在通过描述环境暴露和影响代谢生物标志物，有助于进一步了解暴露和人类健康和疾病。我们使用高通量靶向和非靶向代谢组学技术总结了实验室动物和人类队列研究中与 MDC 相关的代谢生物标志物。包括重金属和有机卤素化合物在内的污染物，尤其是 EDC，反复与代谢紊乱有关，而新出现的污染物，如全氟烷基物质和微塑料也被发现会破坏代谢。此外，我们发现代谢生物标志物的有效鉴定存在重大局限性，尤其是在人体研究中，与对单一化学品的研究相比，对环境暴露的混合效应的毒理学研究也不够充分。因此，为了更好地评估暴露毒理学和健康风险，呼吁致力于研究联合效应和代谢改变的研究工作是及时的。此外，还需要先进的计算和预测工具、代谢生物标志物的进一步验证以及系统和综合研究，以可靠地识别新的生物标志物并阐明毒性机制，并进一步利用暴露组和代谢组分析进行公共卫生和安全管理. 现在是时候呼吁致力于研究联合效应和代谢改变的研究工作，以便更好地评估暴露毒理学和健康风险。此外，还需要先进的计算和预测工具、代谢生物标志物的进一步验证以及系统和综合研究，以可靠地识别新的生物标志物并阐明毒性机制，并进一步利用暴露组和代谢组分析进行公共卫生和安全管理. 现在是时候呼吁致力于研究联合效应和代谢改变的研究工作，以便更好地评估暴露毒理学和健康风险。此外，还需要先进的计算和预测工具、代谢生物标志物的进一步验证以及系统和综合研究，以可靠地识别新的生物标志物并阐明毒性机制，并进一步利用暴露组和代谢组分析进行公共卫生和安全管理.