PROJECT ABSTRACT Noel Theodore Mueller, PhD, MPH, is an Assistant Professor of Epidemiology at the Johns Hopkins Bloomberg School of Public Health (JHSPH). He seeks a K01 Award to obtain the skill set, knowledge and mentored research experience critical for his transition from an early career scientist adept in conducting secondary data analyses in observational epidemiologic cohorts to an independent scientist who analyzes and conducts trials designed to intervene on microbial communities that contribute to cardiometabolic disease. Two essential components of his transition into research independence are hands-on mentored training in 1) the conduct and design of clinical trials and translational microbiome experiments and 2) the analysis and interpretation of high-dimensional microbiome data. The proposed K01 Career Development plan will accomplish these goals. One of the most exciting areas of investigation related to prevention of cardiometabolic disease pertains to the etiologic role of the diet-gut microbiome relationship. Research on the gut microbiome as a target for prevention and therapy is an intriguing arena for public health because unlike the human genome, the gut microbiome is modifiable. Observational studies, murine models and small trials suggest dietary factors may exert many of their health effects in the host through modification of the gut microbiota. However, large rigorous trials in humans are needed to determine the effect of diet interventions on the gut microbiota, and whether changes to the gut microbiota associate with treatment-related improvements in cardiometabolic health. The overall objective of this application is to examine the effects of dietary interventions on the gut microbiota and their short chain fatty acid metabolites in racially-diverse participants in randomized trial settings. A secondary objective is to explore if diet-induced changes in the gut microbiota and their metabolites are associated with changes in blood pressure. Dr. Mueller will carry out this research in the rich training environment of the Johns Hopkins Welch Center for Prevention, Epidemiology and Clinical Research and the JHSPH Department of Epidemiology, under the collaborative and supportive mentorship of Dr. Lawrence Appel, MD, MPH, Director of the Welch Center and Professor of Medicine and Epidemiology at the JHSOM and JHSPH; and co-mentor Dr. Cynthia Sears, MD, Professor of Medicine in the Division of Infectious Disease and Gastroenterology. With the support of Dr. Mueller?s mentor, co-mentor and advisors, he is well positioned to complete the proposed activities. In addition to leading this research, Dr. Mueller will attend courses, workshops, seminars, scientific meetings, and participate in weekly study activities with his mentors. This mentored training will enable Dr. Mueller to grow into an independent researcher, with expertise in the design, conduct and analysis of microbiome studies, focused on understanding the intersecting role of nutrition and the microbiome in cardiometabolic diseases.