Project Summary/Abstract – The University of North Carolina at Chapel Hill Clinical Center The need for more precise nutrition advice is widely recognized, yet specific differences in genetic, epigenetic, microbiome and phenotypic drivers of individual variability to diet are not well known. The National Institutes of Health initiative to fund Nutrition for Precision Health (NPH), powered by the All of Us Research Program, will enable major progress in the field of precision nutrition. Here we propose Nutrition for Precision Health: The University of North Carolina at Chapel Hill Clinical Center (UNC-CC). Because chronic inflammation promotes the pathogenesis of a wide range of diseases, including obesity, type 2 diabetes, and cardiovascular, neoplastic, and neurodegenerative disorders, we draw upon the anti-inflammatory Mediterranean diet as a viable strategy to improve systemic inflammation and reduce risk for many chronic diseases and their complications. A body of literature has emerged that demonstrates both genotypically- and phenotypically-driven differential responses to the Mediterranean diet relative to a range of outcomes. Our proposal will address the critical need to understand variability in physiologic responses to diet, anchored by the theme of inflammation. We emphasize inclusion of a highly diverse sample facilitated by two clinical locations with metabolic kitchens: the UNC Nutrition Research Institute (UNC-NRI) in Kannapolis, NC, and the Chapel Hill campus of UNC (UNC-CH). The UNC-NRI draws from relatively rural communities, and UNC-CH draws from relatively urban communities, both with a substantial proportion of people of color. Specific Aims are: Aim 1. To participate actively in the Year 1 planning process and beyond, engaging across the NPH consortium to collaboratively develop and execute the final study protocol. Aim 2. To execute NPH Module 1. Following participant enrollment into All of Us, we will enroll and complete the Module 1 protocol for a total of 2,000 NPH participants (25% at UNC-NRI; 75% at UNC-CH), including two study visits with a 2-week remote data capture period and a mixed meal challenge test. Aim 3. To execute NPH Module 2. A subset of 500 Module 1 participants will complete a free-living, controlled feeding study of three 2-week diet intervention periods, separated by 3-week washout periods. Diets include: the Mediterranean diet adapted for the US (Med-USA; 40% fat calories, 40% carbohydrate), the Med-USA modified for high healthy fat content (60% fat calories, 20% carbohydrate), and Med-USA modified for high healthy carbohydrate content (20% fat calories, 60% carbohydrate). Differential effects of the diets on outcomes comprising inflammatory markers and metabolic parameters from the mixed meal challenge will be tested across genotypic and phenotypic subgroups, focusing on weight status, age, and diabetes status. The UNC-CC team brings impressive interdisciplinary strength in nutrition (basic science to public health) and has the capacity and experience in complex, multi-site trials to ensure the scientific rigor needed to execute this study. Results will generate predictive algorithms to inform individualized dietary guidance to improve health.

Project Narrative – The University of North Carolina at Chapel Hill Clinical Center The need for more precise nutrition advice is widely recognized, yet specific differences in genetic, epigenetic, microbiome, and phenotypic drivers of individual variability to diet are not well known. The National Institutes of Health initiative to fund Nutrition for Precision Health (NPH), powered by the All of Us Research Program, will enable major progress in the field of precision nutrition. The University of North Carolina at Chapel Hill Clinical Center will include a diverse cohort of adults from rural and urban communities to study the variability in physiologic responses to diet, anchored by the theme of inflammation as a driver of many chronic disease processes.