Understanding how endocrine disruptors and chemical mixtures of concern target the immune system to trigger or perpetuate disease (ENDOMIX)

ENDOMIX项目解决了迫切需要了解内分泌干扰化学品（EDCs）对人类健康的真正影响，以便向监管机构提供信息并向公民提供建议。ENDOMIX将通过揭示EDCs与不良健康结果之间的关联和因果关系来应对这一挑战，重点关注生命过程中多种EDCs的暴露，包括易感性窗口，并利用来自多个欧洲队列的现有可靠数据。模拟现实生活中的EDC混合物如何针对免疫系统启动、触发或持续疾病，结合高通量生物测定，将揭示与健康相关的混合物，其影响将使用突破性的方法进行研究，同时提供有关EDC暴露的机制途径和跨代影响的宝贵信息。这一战略将导致确定易于测量的生物标志物和暴露模式，可用于大样本量，并指示健康终点。最后，我们将提供体外、计算机和体内数据的证据合成，以加强因果推理，并使用证据权重方法生成人工智能辅助知识图。这种独特的循环方法以免疫系统为EDC靶点，只有通过该联盟的跨学科专业知识和广泛获取现有数据和生物样本以及细致的研究设计才能实现。该联盟产生的知识将传播给科学界，为政策制定提供全面的新证据基础，并将传播给所有年龄段的公民，以提高对EDC暴露风险的认识，并促进健康行为。因此，ENDOMIX的结果不仅提供了必要的新知识和理解，而且对社会的健康和福祉具有深远的影响，包括在欧洲卫生保健系统中节省大量资金。

The ENDOMIX project addresses the urgent need to understand the true impact of endocrine disrupting chemicals (EDCs) on human health in order to inform regulators and advise citizens. ENDOMIX will tackle this challenge by revealing associations and causality between EDCs and adverse health outcomes by focusing on exposure to multiple EDCs during life course including windows of susceptibility and making use of already existing robust data from multiple European cohorts. Modelling how real-life EDC mixtures target the immune system to initiate, trigger or perpetuate diseases combined with high throughput bioassays will reveal health-relevant mixtures of concern whose impact will be studied using ground-breaking methodology while delivering valuable information on mechanistic pathways and transgenerational impact of exposure to EDCs. This strategy will lead to the identification of biomarkers and patterns of exposure that are easy to measure, available for big sample sizes, and indicative of health endpoints. Finally, we will provide evidence synthesis of in vitro, in silico and in vivo data for strengthening causal inference and use a weight of evidence approach to generate artificial intelligence-assisted knowledge graphs. This unique loop approach with a novel focus on the immune system as EDC target is only made possible by the consortium’s interdisciplinary expertise and extensive access to existing data and biosamples as well as a meticulous study design. The knowledge generated by this consortium will be disseminated to the scientific community provide a thorough new evidence base for policy making and will reach citizens of all ages to raise awareness about the risks of EDC exposure and promote health-preserving behaviour. Hence, the outcomes of ENDOMIX do not only provide essential new knowledge and understanding but also and have far-reaching implications for the health and well-being of society, including significant savings in European health care systems.