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 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 in all people. The goal of the Nutrition for Precision Health (NPH) research study is to study a large and diverse group of American adults and to use machine learning and artificial intelligence models to understand the individual responses to foods and dietary patterns. NPH is the first ancillary study of the All of Us Research Program. The consortium was formed January 2022 and plans to enroll approximately 10,000 participants into the NPH study. Using a discovery science approach study participants will enroll in either one or two modules; Module 1: a cross-sectional study to characterize daily dietary intake and accompanying nutritional status, biological and other measures over 10 days, as well as physiological responses following a liquid mixed meal tolerance test; Module 2 a crossover randomized study of three 14-day dietary interventions implemented in a community dwelling setting; Module 3 a crossover randomized study of the same three dietary interventions as in Module 2, implemented in a domiciled setting. Participants in these three Modules will contribute simultaneous, multimodal measurements (e.g., dietary assessment, anthropometric, physiological, behavioral, social, and contextual measurements) carefully selected for their relevance to understanding responses to foods, including nutrients, food components, and dietary patterns. The rich set of data and biospecimens 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 importantly address health disparities.

Histone acetylation is an important epigenetic modification that controls pathological cardiac hypertrophy (enlargement), fibrosis (scarring) and heart failure (HF). Over the last several years, our lab and others have shown that histone deacetylase (HDAC) inhibition attenuated cardiac hypertrophy and fibrosis that contributed to improved cardiac function. Recent interest in our lab has further shown that food bioactives can serve as HDAC inhibitors to ameliorate pathological cardiac hypertrophy. Indeed, we report that emodin, an antraquinone, serves as an HDAC inhibitor that normalized global changes in gene expression in stress-induced cardiac myocytes as well as attenuated pathological cardiac hypertrophy and fibrosis in hypertensive male and female mice. However, recent reports show that gut bacteria and the liver often metabolize parent compounds, and thus few parent compounds reach their intended target tissues, e.g. the heart following oral consumption. Thus, it has become critical that new research studies focus on understanding how food bioactives interact with the microbiome in diseased and healthy states, as well as identify metabolites that affect epigenetic signatures in target tissues. Indeed, reports demonstrate changes in the gut microbiome and circulating metabolites in response to hypertension. We report that emodin increased the abundance of cardioprotective bacteria (e.g. Akkermansia) in hypertensive mice, and rapidly (within 3 days) decreased microbial diversity, while increasing the abundance of cardioprotective bacteria specifically in the colon (e.g. Akkermansia) as well as health-promoting bacteria (e.g. Roseburia) throughout the gut. Future work will need to establish if parent compounds directly drive bacterial growth or indirectly affect mucus production and pH regulation for healthy bacterial growth, or if food bioactive metabolites elicit these affects. In addition, future work will need to investigate the link between food bioactives and the microbiome-epigenome axis in CVDs. However, these data show that microbial changes occur rapidly with cardioprotective food bioactives and that these compounds can improve bacterial abundance of known cardioprotective species in both healthy and hypertensive mice.