Dietary Choline, Gut Microbiota, and Susceptibility for Chronic Kidney Disease

 描述（由申请人提供）：慢性肾脏疾病（CKD）影响许多患者，特别是在老年人群中，发病率高，导致公共卫生费用高昂 问题.人们越来越认识到早期发现和预防的重要性，但迄今为止，有效的预防措施很少。我们有令人兴奋的初步数据表明，一种新的饮食诱导的肠道微生物群介导的途径可能是CKD易感性和不良预后的直接因素。在本申请中，我们将在生物化学、动物模型和人类临床水平上询问饮食诱导的肠道微生物途径的各个方面。我们将研究特定的慢性饮食暴露在不利的CKD进展风险中的作用。我们将研究肠道微生物在CKD易感性中的作用，以及这一过程中的特定微生物酶系统。我们还将进行大规模的人体临床研究，测试在循环中检测到的肠道微生物产生的产物是否可预测CKD发生和进展的事件风险。最后，我们将探讨新型抗微生物靶向治疗和饮食调整预防饮食诱导的CKD的潜在疗效。成功完成拟议的研究应提供重要的机制见解，有助于CKD发展的新途径，以及开发新的诊断测试和治疗方法，以预防CKD。

 DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) affects many patients, particularly in the aging population with significant morbidity resulting in a costly public health problem. There is increasing realization for the importance of early detection and prevention, but to date there are few effective preventive measures. We have exciting preliminary data that suggest a novel, diet-induced gut microbiota-mediated pathway may serve as direct contributor to CKD susceptibility and adverse prognosis. In the present application we will interrogate each facet of the dietary-induced gut microbial pathway at the biochemical, animal model, and human clinical level. We will examine the role of specific chronic dietary exposures in risk for adverse CKD progression. We will examine the role of gut microbes in CKD susceptibility, and specific microbial enzyme systems in this process. We also will perform large scale human clinical studies testing whether gut microbial generated products detected in the circulation predict incident risk for development and progression of CKD. Finally, we will explore the potential efficacy of novel anti-microbial targeted therapy and dietary modifications for the prevention of dietary-induced CKD. Successful completion of the proposed studies should provide both important mechanistic insights into a new pathway that contributes to CKD development, as well as develop novel diagnostic tests and therapeutic approaches for the prevention of CKD.