DNA and metabolomic markers of diets rich in polyphenols or processed foods

About This Grant

PROJECT SUMMARY/ABSTRACT Despite the clinical importance of diet, it remains notoriously difficult to measure. Poor diet quality is estimated to account for a large percentage of deaths from type 2 diabetes and cardiovascular disease. The mainstay of dietary assessment has been self-reported intake, though decades of research have documented an array of measurement challenges, which can bias associations and limit our ability to detect dietary components relevant for health. These challenges have had a significant negative impact on the field, with growing skepticism about the results from nutritional epidemiologic studies. The critical need for development of improved markers of diet is well-recognized, as highlighted in the 2020-2030 Strategic Plan for NIH Nutrition Research, and funding of the Dietary Biomarkers Development Consortium, and a dietary assessment center within the Nutrition for Precision Health ancillary study to the All of Us Research Program. Biomarkers are promising alternatives to self-report intake assessments. Over the past decade, a large and growing literature has advanced our understanding of metabolites that derive from dietary components. Large-scale studies reveal enormous potential for metabolomics to advance the study of dietary biomarker development and precision nutrition, given individual variability in metabolite production and excretion. Recently, investigators have leveraged a novel method used by wildlife ecologists to measure dietary intake by mapping fecal DNA sequences to reference databases of plant and animal genes. The method is appealing, as it may have more recovery-like properties than metabolites, and errors in intake estimates are likely to be independent of errors in other approaches. Published results, and findings from our preliminary analyses, are compelling, but significant gaps remain. Importantly, there has been no rigorous test using controlled intake of known food quantities to evaluate the approach. Of the few publications on DNA sequencing in humans, none have integrated metabolomics data. We address these gaps through controlled feeding to rigorously evaluate the use of fecal DNA sequencing and untargeted metabolomics for development of dietary biomarkers. Thirty-six participants will be recruited from the Kannapolis, NC, region, and randomly allocated to one of two test diets: low vs high in processed food (18 participants each). Within diet arms, participants will be randomized to one of a sequence (order) of receiving three food challenges: blueberries, chocolate, blueberries and chocolate. Food challenges will occur on the first of four days of test diet-controlled feeding. Improving measurement of dietary intake is foundational to the field. It is even more critical in the age of precision nutrition, as self- reported intake will not be sufficient for delineating sources of individual variability in dietary effects. Proposed research activities have the potential to transform the field of dietary assessment and biomarker development through the identification of novel objective markers of intake.