Nutrigenomics and metabolomics will change clinical nutrition and public health practice: insights from studies on dietary requirements for choline

Abstract

Science is beginning to understand how genetic variation and epigenetic events alter requirements for, and responses to, nutrients (nutrigenomics). At the same time, methods for profiling almost all of the products of metabolism in a single sample of blood or urine are being developed (metabolomics). Relations between diet and nutrigenomic and metabolomic profiles and between those profiles and health have become important components of research that could change clinical practice in nutrition. Most nutrition studies assume that all persons have average dietary requirements, and the studies often do not plan for a large subset of subjects who differ in requirements for a nutrient. Large variances in responses that occur when such a population exists can result in statistical analyses that argue for a null effect. If nutrition studies could better identify responders and differentiate them from nonresponders on the basis of nutrigenomic or metabolomic profiles, the sensitivity to detect differences between groups could be greatly increased, and the resulting dietary recommendations could be appropriately targeted. It is not certain that nutrition will be the clinical specialty primarily responsible for nutrigenomics or metabolomics, because other disciplines currently dominate the development of portions of these fields. However, nutrition scientists' depth of understanding of human metabolism can be used to establish a role in the research and clinical programs that will arise from nutrigenomic and metabolomic profiling. Investments made today in training programs and in research methods could ensure a new foundation for clinical nutrition in the future.

FIGURE 1

DNA methylation can silence gene expression. Methylation of cytosine located in cytosine-guanosine groupings in gene promoter regions (called 5′-CpG-3′ islands) attracts capping proteins that hinder access to the gene for the transcription factors that normally turn on gene expression and formation of messenger RNA (mRNA). When the transcription factor does not bind to the promoter area of the gene, transcription of mRNA does not occur, and the gene is silenced.

FIGURE 2

A theoretical example of what the informatics tools may look like that will make nutrigenomics and metabolomics accessible to nutrition scientists and clinicians. After appropriate statistical tests and filtering, data from nutrigenomic, epigenetic, and metabolomic platforms can be overlaid on the metabolic map that we are familiar with. By selecting an area of the metabolic map, the user can zoom in on the region and see a presentation of changes in metabolite concentrations, enzyme activities, and perhaps flux rates with color coding to indicate direction of change. Information on changes in DNA expression (E), gene methylation (M), and gene SNPs also can be presented by using similar color coding. By selecting the metabolite, enzyme, or gene box, an investigator would be able to examine the exact values and variances and perhaps even to examine the raw data. Another level of the informatics program would summarize all of the related changes by pathway and present information on false discovery and significant difference statistics. Finally, a summary of appropriate diet recommendations would be presented.