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

• 批准号: 9353782
• 负责人: Amanda Hyre Anderson
• 金额: $ 56.54万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 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/9353782
• 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; 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; Prospective cohort; Proteins; Renal clearance function; Renal function; Risk; Role; Serum; Shotguns; Urea; Urease; Vascular Diseases; Virus; adverse outcome; base; clinical development; cohort; experience; follow-up; fungus; gut microbiome; gut microbiota; insight; metabolome; microbial; microbial host; microbiome; mortality; nitrogen balance; prevent; rRNA Genes; small molecule; trimethyloxamine; urinary

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.

慢性肾脏疾病（CKD）可能会改变人类宿主与其之间的稳态关系 肠道微生物居民（即肠道微生物群），尿素递送到 肠道微生物群，饮食的改变以及小分子的尿排泄减少 由肠道菌群产生。结果，肠道菌群的组成及其 CKD患者可能会改变代谢产物副产品。我们提出了一组相互关联的特定 旨在检查CKD，肠道微生物群和粪便代谢组之间的关联 代谢组，以及使用纵向前瞻性队列的临床结果的发展 慢性肾功能不全队列（CRIC）研究。此外，我们提出了少量介入 研究的研究，然后重新填充肠道菌群，在其他CKD群体中 患者鉴定肠道循环中积累的肠道副产品。结果 我们的研究将为干预措施（例如调节饮食）提供新的见解，这些干预措施可能会改变 肠道菌群的代谢组，以帮助预防和/或治疗与 CKD的开发。