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

 描述(申请人提供)：慢性肾脏疾病(CKD)影响许多患者，特别是在老龄化人口中，发病率很高，导致昂贵的公共健康 有问题。人们越来越认识到及早发现和预防的重要性，但迄今几乎没有有效的预防措施。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区系介导的途径可能是CKD易感性和不良预后的直接贡献者。在目前的应用中，我们将在生化、动物模型和人类临床水平上询问饮食诱导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CKD不良进展风险中的作用。我们将研究肠道微生物在CKD易感性中的作用，以及特定的微生物酶系统在这一过程中的作用。我们还将进行大规模的人体临床研究，测试循环中检测到的肠道微生物产物是否可以预测慢性肾脏病的发生和进展的风险。最后，我们将探索新型抗微生物靶向治疗和饮食调整在预防饮食诱导的CKD方面的潜在疗效。拟议研究的成功完成将为促进CKD发展的新途径提供重要的机制见解，并为预防CKD开发新的诊断测试和治疗方法。

 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.