The Gut Microbiome and The Metabolome in Chronic Kidney Disease

慢性肾脏病的肠道微生物组和代谢组

基本信息

批准号：
9176606
负责人：
Amanda Hyre Anderson
金额：
$ 59.33万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-20 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9176606
关键词：
Amino Acids Ammonia Animals Archaea Bacteria Blood Circulation Cardiovascular Diseases Cessation of life Choline Chronic Kidney Failure Chronic Kidney Insufficiency Clinical Cohort Studies Comorbidity Consumption Coronary Cresol Development Diet Disease Disease Progression End stage renal failure Equilibrium Excretory function Feces Genomics Glomerular Filtration Rate Goals Health Human Individual Intervention Intervention Studies Intestines Lead Maintenance Metagenomics Microbe Outcome Participant Patients Pattern Plasma Play Population Production Proteins Renal clearance function Renal function Risk Role Serum Shotguns Urea Urease Vascular Diseases Virus adverse outcome base cohort experience follow-up fungus gut microbiome gut microbiota insight metabolome microbial microbial host microbiome mortality nitrogen balance prevent prospective rRNA Genes small molecule trimethyloxamine urinary

项目摘要

Chronic kidney disease (CKD) may alter the homeostatic relationship between human hosts and their intestinal tract microbial inhabitants (i.e., the gut microbiota) due to the enhanced delivery of urea to the gut microbiota, alterations in diet, and the decrease in urinary excretion of small molecules produced by the gut microbiota. As a result, both the composition of the gut microbiota and its metabolite byproducts may be altered in patients with CKD. We propose a set of inter-related specific aims to examine the association between CKD, gut microbiota and the fecal metabolome, the plasma metabolome, and the development of clinical outcomes using a longitudinal prospective cohort within the Chronic Renal Insufficiency Cohort (CRIC) Study. In addition, we propose a small interventional study to eradicate and then re-populate the gut microbiota among an additional population of CKD patients to identify gut-derived byproducts that accumulate in the systemic circulation. The results of our study will provide new insights into interventions, such as modulation of diet, that may alter the metabolome of the gut microbiota to help prevent and/or treat diseases associated with the development of CKD.

慢性肾脏病（CKD）可能会改变人类宿主与其体内稳态的关系由于尿素的输送增强，肠道微生物居民（即肠道微生物群）肠道微生物群、饮食改变以及小分子尿液排泄减少由肠道微生物群产生。因此，肠道微生物群的组成及其 CKD 患者的代谢副产物可能会发生改变。我们提出了一套相互关联的具体旨在检查 CKD、肠道微生物群和粪便代谢组、血浆之间的关联代谢组学，以及使用纵向前瞻性队列研究临床结果的发展慢性肾功能不全队列 (CRIC) 研究。此外，我们建议进行小型介入治疗研究根除然后重新填充额外 CKD 人群的肠道微生物群患者识别在体循环中积累的肠道衍生副产物。结果我们的研究将为干预措施提供新的见解，例如饮食调节，这可能会改变肠道微生物群的代谢组有助于预防和/或治疗与肠道菌群相关的疾病 CKD 的发展。