Imminent Disease Prediction and Prevention at the Environment Host Interface (IMMEDIATE)

近期的目标是调查和探索饮食-微生物-免疫代谢-轴作为从健康到疾病过渡的传感器，并评估维持个人福祉的策略。慢性炎症是大多数疾病的主要根源。了解器官功能障碍或损害之前的这一过程，并在症状前阶段确定生物标记物和从健康向疾病过渡的风险以及复原力因素，将使有针对性和个性化的干预措施能够预防不可逆转的器官损害。肠道微生物区系的代谢产物是饮食、微生物区系和宿主之间的关键信使，维持着促炎和抗炎的平衡。我们的研究利用了Immediate财团提供的尖端组学技术，结合现有的临床数据和正在进行的观察性研究的生物标本，招募了处于疾病前期阶段但具有基本上不同的环境和饮食调节因素的“健康”受试者和个体，包括一组肾移植受者，在这些受者中，肾功能已“重置至基线”。通过使用人工智能算法，识别临床和组学衍生的生物标记物将产生慢性炎症的个性化风险/弹性评分，从而更好地预测个人向疾病过渡的风险。将对抗炎微生物Akkermansia visiniPhila进行一项概念验证干预研究，以测试微生物-代谢物-免疫轴的偏转是否可以在生物标记物水平上逆转，但也可以在临床结果和整体福祉方面逆转。由Immediate联盟与患者组织合作开发的移动应用程序跟踪许多与生活方式相关的措施，并就这些方面提供指导和反馈，将使个人能够采用这些基于知识的健康干预措施，并将其整合到自己的生活中，从而自我管理自己的健康。

IMMEDIATE aims to investigate and explore the diet-microbiome-immunometabolism-axis as a sensor for health-to-disease transition and evaluate strategies to maintain an individual’s well-being. Chronic inflammation is the major root of most diseases. Understanding of this process preceding organ dysfunction or damage and identification of biomarkers in the pre-symptomatic stage and risk but also resilience factors of health-to-disease transition will enable targeted and personalized interventions to prevent irreversible organ damage. Metabolites of gut microbiota are key messengers between diet, microbiota and host, maintaining the balance of pro- and anti-inflammation. Our study takes advantage of cutting-edge omics technologies available within the IMMEDIATE consortium in conjunction with available clinical data and biospecimens from ongoing observational studies, enrolling “healthy” subjects and individualsin the pre-disease stage but with largely distinct environmental and dietary modulators, including a cohort of kidney transplant recipients in whom renal function has been “reset to baseline”. The identification of clinical and omics-derived biomarkers will – by employing AI algorithms - yield a personalized risk / resilience score of chronic inflammation and thus a better prediction of an individual’s risk of transition towards disease. A proof-of-concept intervention study with the anti-inflammatory microbe Akkermansia muciniphila will be conducted to test whether deflections of the microbiome-metabolite-immune axis can be reverted on the biomarker level but also with respect to clinical outcomes and overall well-being. Mobile apps developed by the IMMEDIATE consortium in collaboration with patient organizations tracking numerous lifestyle-related measures and providing guidance and feedback on these aspects will empower individuals to adopt and integrate these knowledge-based health interventions into their own lives, hereby selfmanaging their own health.