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

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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.