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

ADPKD 患者饮食干预后的代谢组和微生物组分析

• 批准号: 10665586
• 负责人: Cortney Steele
• 金额: $ 3.93万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10665586
• 关键词: 16S ribosomal RNA sequencing; Affect; Age; Age Years; Autosomal Dominant Polycystic Kidney; Biometry; Body Weight decreased; Body Weights and Measures; Caloric Restriction; Choline; Clinical; Clinical Research; Collaborations; Colorado; Communication; Control Groups; Cystic kidney; Data; Development; Dialysis procedure; Diet; Dietary Intervention; Disease Progression; Eating; Enrollment; Epidemiology; FDA approved; Fasting; Feces; Foundations; Funding; General Population; Genetic; Genetic Diseases; Glomerular Filtration Rate; Glucose; Goals; Growth; Health; Healthy Eating; Height; Impairment; Individual; Inherited; Insulin; Insulin Resistance; Intervention; Intervention Trial; Kidney; Kidney Diseases; Kidney Transplantation; Knowledge; Lipoproteins; Liquid substance; Measures; Medical; Mentors; Metabolism; Modeling; Nephrology; Obesity; Outcome; Outcome Measure; Overweight; PKD2 gene; Parents; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Physiology; Plasma; Population; Postdoctoral Fellow; Productivity; Publications; Randomized, Controlled Trials; Regimen; Renal function; Research; Research Project Grants; Sampling; Science; Site; Taxonomy; Time-restricted feeding; Training; Universities; Weight Gain; abdominal fat; cardiometabolism; career; career development; clinically significant; cohort; comparison control; dietary; effective therapy; experience; feeding; gut microbiota; improved; improved outcome; indexing; individual response; lifestyle intervention; metabolome; metabolomics; microbiome; microbiome composition; microbiota profiles; novel; nutrition; obesity development; predict responsiveness; predictive marker; programs; prospective; research and development; response; side effect; skills; tolvaptan; treatment strategy; trimethylamine; trimethyloxamine; urinary; weight maintenance

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.

项目概要/摘要 申请人 Cortney Steele 博士完成了临床生理学和新陈代谢方面的研究生培训。博士。 斯蒂尔的长期目标是开发一个独立的研究项目，研究营养对健康的影响。 临床人群的健康结果，包括肾病患者。检查微生物组和 针对饮食变化的代谢组分析并将这些指数与疾病进展联系起来 提供有洞察力的信息，可促进常染色体有效治疗策略的制定 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 博士后研究调查：1）肠道微生物群和血浆代谢组如何对饮食做出反应 对 ADPKD 患者进行干预； 2) 肠道微生物群和代谢组学特征与疾病的关系 进展和健康措施。斯蒂尔博士和她的指导团队开发了一个全面的 培训计划将建立在她之前的临床研究经验的基础上，同时扩展她的知识 多囊肾、营养干预和肥胖。 Steele 博士的主要培训目标包括：1) 提高她的能力 肾脏病学、营养/代谢、流行病学和生物统计学相关知识； 2）推进新 技术研究技能和合作； 3）先进的干预试验经验，既 远程和现场； 4）完善她的专业发展和研究网络； 5）拓展科学 沟通技巧、出版记录和资助能力。为了实现这些目标，斯蒂尔博士提出 研究项目将： 1.A）表征肠道微生物群和血浆代谢组的纵向变化 两项正在进行的针对 ADPKD 患者的随机对照试验对饮食干预的反应 超重或肥胖（DCR，每日热量限制为体重维持要求的 34% 和 TRF，时间限制喂养，将进食限制在每天 8 小时的喂养窗口内），B) 评估 血浆代谢组和肠道微生物群特征与饮食反应性测量的关联 干预措施，包括体重减轻百分比和腹部肥胖的△； 2）评估肠道的关联性 微生物群和代谢组学特征以及肾脏疾病进展的指标和测量 心脏代谢健康。这项研究将发表几篇第一作者出版物并提供初步数据 支持持续指导的职业发展资金（即 K01）。该项目产生的数据也将 为持续研究提供更有针对性的方法，旨在了解微生物组的组成和 ADPKD 人群的代谢组学。斯蒂尔博士还将有大量合作机会 在她的赞助商在科罗拉多大学安舒茨医学校区的研究项目中。总的来说， 这些活动将为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奠定基础。