Metabolome and Microbiome Profiling in Response to Dietary Interventions in Patients with ADPKD

项目摘要/摘要 申请者Cortney Steele博士完成了临床生理学和新陈代谢的研究生培训。Dr。 斯蒂尔的长期目标是开发一项独立的研究计划，研究营养对 临床人群的健康结果，包括肾脏疾病患者。检查微生物组和 代谢组谱对饮食变化的反应并将这些指标与疾病进展联系起来将 提供有洞察力的信息，以促进常染色体有效治疗策略的发展 显性多囊肾病(ADPKD)人群。为了帮助斯蒂尔博士实现这一目标，她发起了 博士后研究：1)肠道微生物区系和血浆代谢组对饮食的反应 对ADPKD患者的干预；以及2)肠道微生物区系和代谢组谱与疾病的关系 进展和健康措施。斯蒂尔博士和她的指导团队开发了一种全面的 培训计划将建立在她以前的临床研究经验的基础上，同时扩大她对 PKD、营养干预和肥胖。斯蒂尔博士S的主要培训目标包括：1)提高她 有关肾病学、营养/代谢、流行病学和生物统计学的知识；2)先进的新知识 技术研究技能和合作；3)进行干预试验的高级经验， 远程和现场；4)完善她的专业发展和研究网络；5)扩大科学 沟通技巧、出版记录和从容精神。为了实现这些目标，斯蒂尔博士提出了 研究项目将：1)表征肠道微生物区系和血浆代谢组的纵向变化 ADPKD和ADPKD患者正在进行的两项随机对照试验中饮食干预的反应 超重或肥胖(DCR，每日34%的卡路里限制，超出体重维持要求 和TRF，限时进食将进食限制在8小时/天的进食窗口)，B)评估 血浆代谢组和肠道微生物区系与饮食反应性的关系 干预措施，包括体重减轻百分比和腹部肥胖症；2)评估肠道与 微生物区系和代谢组谱与肾脏疾病进展的指标和措施 心脏代谢健康。这项研究将导致几个第一作者的出版物，并提供初步数据 支持持续的辅导式职业发展资助(即K01)。该项目产生的数据还将 为继续研究提供更有针对性的方法，旨在了解微生物组组成和 ADPKD人群的代谢组学研究。斯蒂尔博士还将有很多机会成为合著者 在她的赞助商在科罗拉多大学安舒茨医学院的研究项目中。总而言之， 这些活动将提供一个前所未有的机会来发展斯蒂尔博士的研究知识和 技能，同时为富有成效的独立研究生涯提供基础。

PROJECT SUMMARY/ABSTRACT The applicant, Dr. Cortney Steele, completed her graduate training in clinical physiology and metabolism. Dr. Steele's long-term goal is to develop an independent research program studying the impact of nutrition on health outcomes in clinical populations, including kidney disease patients. Examining microbiome and metabolome profiling in response to dietary changes and relating these indices to disease progression will provide insightful information that may facilitate development of effective treatment strategies in the autosomal dominant polycystic kidney disease (ADPKD) population. To help Dr. Steele meet this goal, she has initiated postdoctoral research to investigate: 1) how the gut microbiota and plasma metabolome respond to dietary interventions in those with ADPKD; and 2) how gut microbiota and metabolomic profiles relate to disease progression and health measures. Dr. Steele and her mentoring team have developed a comprehensive training plan that will build upon her previous in clinical research experience, while expanding her knowledge of PKD, nutritional interventions, and obesity. Dr. Steele’ s primary training objectives include: 1) improve her knowledge related to nephrology, nutrition/metabolism, epidemiology, and biostatistics; 2) advance new technical research skills and collaborations; 3) advance experience in conducting intervention trials, both remote and on-site; 4) improve her professional development and research network; and 5) expand science communication skills, publication record, and grantsmanship. To achieve these goals, Dr. Steele’s proposed research project will: 1.A) characterize longitudinal changes in the gut microbiota and plasma metabolome in response to dietary interventions in two ongoing randomized control trials in patients with ADPKD and overweight or obesity (DCR, daily caloric restriction of 34% per day from weight maintenance requirements and TRF, time-restricted feeding restricting eating to a feeding window of 8 hrs/day), B) Evaluate the association of plasma metabolome and gut microbiota profiles with measures of responsiveness to dietary interventions, including % weight loss and △ in abdominal adiposity; 2) Evaluate the association of gut microbiota and metabolomic profiles with indicators of kidney disease progression and measures of cardiometabolic health. This research will lead to several first-author publications and provide preliminary data to support continued mentored career development funding (i.e., K01). Data arising from this project will also lead to more targeted approaches for continued research aimed at understanding microbiome composition and metabolomics in the ADPKD population. Dr. Steele will also have numerous opportunities for co-authorship within her sponsor’s research program at the University of Colorado Anschutz Medical Campus. Collectively, these activities will provide an unprecedented opportunity to develop Dr. Steele’s research knowledge and skills, while providing a foundation for a productive independent research career.