PROJECT SUMMARY Epidemiological and clinical studies support an important role of nutrition in health. However, nutrition research is limited by bias due to self-reported diet data and inter- and intra-individual variation. High-throughput `omic' profiling techniques combined with advanced remote real-time data collection now enable comprehensive studies of individual responses to diet thereby creating opportunities for personalized nutrition advice. Our overall goal is to facilitate the Nutrition for Precision Health (NPH) Consortium by leveraging our existing Illinois Precision Medicine Consortium (IPMC) infrastructure to enroll All of Us Research Program (AoURP) participants in the discovery nutrition science study involving three diet modules. Proposed is investigation of specific elements of a Dietary Approaches to Stop Hypertension (DASH) diet with blood pressure (BP) as the primary outcome. BP is regulated by a complex network of mechanisms under the influence of genetic and environmental factors, and high BP is recognized as the leading modifiable risk factor for cardiovascular disease, cerebrovascular disease, kidney disease and all-cause mortality worldwide. DASH diet adherence has consistently documented reduced BP, independent of baseline calorie or sodium intake. Although older, hypertensive and Black persons show greater BP responses to DASH adherence and reduced dietary sodium intake, inter-individual variability is observed and remains unexplained. In Module 1, we will follow 2,000 AoURP participants for 14 days to examine baseline diet and physiological responses to test-meal challenges hypothesized to elicit variable physiological and metabolomic responses based on individual cardiometabolic, genetic and gut microbial status. We then examine responses to three 14-day intervention periods involving DASH-type diets among 400 consenting Module 1 participants in a free-living controlled feeding study (Module 2) and in 200 Module 1 participants in a domicile controlled feeding study (Module 3). The three intervention diets are isocaloric, sodium equivalent and include: i) DASH-Standard, ii) DASH-FFF, specifying fruits, flavonoids and fat and DASH-PP, emphasizing plant protein. Each diet has distinctive nutritive properties that influence BP regulation and each will elucidate diverse physiological, metabolomic, and microbiomic responses that are modified by cardiometabolic and genetic status. Our three IPMC clinical sites including Northwestern University, the University of Chicago, and the Illinois Institute of Technology span wide yet geographically distinct service areas in ethnically and socioeconomically diverse Chicago communities, thereby offering targeted enrollment of demographically diverse participants. This research in collaboration with the NPH consortium initiates fundamental causal and mechanistic insight into the role of the DASH-type diet in BP regulation with potential to discover novel biological pathways underlying risks for developing high BP. This advanced knowledge can inform unprecedented personalized diet recommendations to prevent and treat the massive public health burden off hypertension.

PROJECT NARRATIVE We use the existing Illinois Precision Medicine Consortium infrastructure to enroll All of Us Research Program participants to implement DASH diet modules targeting blood pressure reduction. Our clinical study in collaboration with the NPH consortium will provide causal and mechanistic insight into the role diet plays in BP regulation and will provide a preventive foundation for personalized diet recommendations for BP control.