PROJECT SUMMARY Nutrition is at the epicenter of human health and disease. However, our current “one size fits all” approach to clinical nutrition is failing a large segment of the population. Individual factors including genetics, metabolism, physiology, microbiome, behavior, the built in and contextual environment all underlie the inherent variability in response to diets. Exciting new research shows that machine learning algorithms can integrate this complex information and predict how someone responds to a given diet. If validated, this innovative approach will provide a radical change in the delivery of personalized nutrition prescriptions to promote health and treat chronic diseases. The goal of the “Nutrition for Precision Health (NPH), powered by All of Us” consortium is to generate a rich database from a diverse population to develop a first-of-its-kind diet prediction algorithm. The aim of the Louisiana-Arizona Nutrition for Precision Health Center (LAAZ-NPH), consisting of LSU-Pennington Biomedical (PBRC) in Baton Rouge, LSU-Health Sciences Center (LSUHSC) in New Orleans, and the NIDDK- Phoenix Clinical Center (PIMC) in Phoenix, is to participate in the NPH consortium as a clinical center to recruit, enroll and retain more than 2000 participants in the three planned study modules. In Module 1, 2,000 from the All of Us Research Program in Louisiana (Baton Rouge and New Orleans; 600 each) and Arizona (Phoenix; 800) will be enrolled in a 10-day prospective, observational study. Following the completion of Module 1, 300 study participants who meet specified eligibility criteria for enrollment to the controlled feeding studies, will participate in Module 2 (PBRC, LSUHSC and PIMC; 100 each) and at least 100 in Module 3 (PBRC and PIMC only; ≥50 each). Module 2 is a controlled feeding study in an outpatient setting with 300 study participants while Module 3 is a controlled feeding study in an inpatient setting with at least 100 study participants that completed Module 1. Modules 2 and 3 will use a block randomization cross-over study design to evaluate the individual response to three, 14-day isocaloric diet interventions. The three intervention diets (a combination of the Mediterranean and DASH diet (MEDASH); a sustainable predominantly plant-based Flexitarian diet (FLEX) and a Highly Preferred Western Diet (HPWD) will be separated by a 7-21 day wash out periods. Our primary endpoint is the post-prandial plasma glucose response (PPGR) to a standardized mixed meal tolerance test (MMTT) as measured by the incremental glucose area under the curve over 180 min (AUC180). Secondary endpoints are biomarkers of cardiometabolic health including insulin resistance and a metabolic syndrome score. The rich set of data and biospecimens collected by our proposed center will be used to inform paradigm shifting approaches that enable large-scale delivery of personalized dietary prescriptions to promote general health, delay cardiometabolic diseases, and impo...