Nutrigenomics and Personalized Nutrition: Science and Concept

Martin Kussmann; Laurent B. Fay

Disclosures

Personalized Medicine. 2008;5(5):447-455. 

In This Article

Nutrigenomics & Nutri(epi)genetics

Our diet interacts with our genes. Nutrigenomics asks how dietary components influence gene expression, while nutrigenetics asks how our genetic makeup makes us respond or not to dietary intervention.[7] Nutrigenomics assesses dietary influence at gene and protein expression and metabolite level and derives omics profiles typical for a nutritional intervention or status. Nutrigenetics typically characterizes SNPs with regards to their frequency in a given population and to their relevance for metabolic health or disorders.[7] For example, G-protein-located SNPs have been shown to predispose people in certain populations to metabolic syndrome, atherosclerosis or functional dyspepsia.[8] Furthermore, not only single-base mutations but also varying copy numbers for a given gene account for interindividual variability at genome level.[9] However these so-called copy-number polymorphisms or copy-number variants have not yet, to our knowledge, been put in a nutritional perspective.

Nutrigenomics stands for the dynamically evolving field of diet–gene interactions.[10] It is advancing thanks to technological progress at all three omics levels and profits from increasing correlation and integration of transcript, protein and metabolite data.[6] However, the latter requires understanding of the timing of the events of gene transcription, protein expression and metabolite generation, as well as the further maturation of informatic tools for integrative data analysis.[11]

An impressive example of nutrigenomics applied to the improvement of human health at the population level is the European 'Diet, Obesity and Genes' (DiOGenes) project,[101] the acronym standing for. The overall objective is to reduce the widespread health problems of overweight, obesity and related comorbidities among European consumers. In order to adequately address this challenging goal, DiOGenes investigates how key genomic and dietary lifestyle factors combine in different people to precipitate weight gain, weight regain and its associated comorbidities. In particular, the consortium deploys an integrated scientific approach to identify key psychological, lifestyle and genetic factors, as well as biomarkers, that will provide a scientific basis for predicting whether a subject will maintain a healthy weight or not. Six research, technology and development lines integrate nutrigenomics, nutrigenetics, population studies, food technology and consumer behavior. The final deliverable of the project is to increase wellbeing among European consumers by exploiting the new knowledge generated to promote safe, high-quality diets, minimizing risks of overweight and obesity.

Nutrigenomics, with its potential to deliver dynamic biomarkers for nutrition and health status as well as ingredient activity and efficacy, is increasingly being linked to nutri(epi)genetics, which can furnish long-term or static biomarkers for individual disposition towards diet and nutritional imprinting. Nutrigenetics will certainly contribute to improved study cohort definition. The standardization initiatives launched in the omics community will increasingly be complemented by equally indispensable efforts of harmonizing dietary interventions in terms of, for example, standardized diets with defined micro- and macronutrient content and origin. An international consortium is beginning to address the annotation of the human genome according to nutritional criteria.[12]

Epigenetics does not look at DNA sequence variation but at post-translational modifications of DNA-binding proteins (e.g., histones and chromatin)[13,14] and of DNA itself (methylation).[15] These biochemical alterations of the genome and the 'packaging' molecules influence DNA accessibility and, thereby, transcription. These effects can last for a long period in life and can even be transmitted from one generation to another.[16] Furthermore, heritable, environmentally induced epigenetic modifications have been shown to underlie reversible transgenerational alterations in phenotype.[17]

While monozygous twins have the same genotype, most monozygotic twin pairs are not identical, but are phenotypically discordant. One possible explanation for this finding is the existence of epigenetic differences. Fraga et al. examined global and locus-specific differences in DNA methylation and histone acetylation of a large cohort of monozygotic twins.[18] They discovered that twins are epigenetically indistinguishable during the early years of life, but older monozygous twins exhibited differences in content and genomic distribution of 5-methylcytosine DNA and histone acetylation, the latter affecting their gene-expression pattern.

Whereas many of the earlier studies had assumed that SNPs were the main source of human genetic variability, an increasing body of evidence now suggests the importance of additional layers of variability, including copy-number polymorphisms and epigenetic regulation, such as DNA methylation. Many complex diseases, such as inflammatory bowel disease (Crohn's disease and ulcerative colitis), have been shown to be related to SNPs on particular chromosomal regions, but are also associated with copy-number variation of certain other genes.[19] Such discoveries suggest that a detailed description of the genetic background of complex diseases is a challenging but necessary objective in order to better prevent pathological development by, for example, adapted diets.

Epigenetics is just beginning to reveal its possible implications in nutrition. One aspect in this regard is the astonishing imprinting effect that nutrition can exert on a genome:[20] DNA methylation appears to provide a format for long-term dietary (re-)programming of the genome,[21] suggesting that nutritional supplementation may have unexpected adverse consequences on gene regulation in humans, and that well-adapted diets already applied at pre- and post-natal stage may exert a fundamental and long-lasting positive impact. Some evidence shows that chronic diseases/conditions in adulthood are due to persistent perturbations/influences during early-life nutrition.[22]

Even cognitive development seems to be amenable to genetically counseled nutritional intervention. Studies have shown that nutrients, such as n-3 long-chain polyunsaturated fatty acids, can affect brain development and, therefore, cognitive function. A recent publication showed that the association between breastfeeding and IQ is moderated by a genetic variant in a gene involved in the control of fatty acid pathways.[23]

As diet is the most prominent life-long environmental impact on human health and as, with prolonging lifespan and changing lifestyle in developed countries, chronic diseases become more prevalent, nutrigenomics and nutrigenetics are key scientific platforms to promote health and prevent disease through nutrition that better meets the requirements and constraints of consumer groups with specific health conditions, particular lifestyles and in certain stages of life. Eventually, the nutrigenomics-rooted concept of personalized nutrition may translate into the development of new food products that target, if not individuals, at least groups of people with similar metabolic phenotypes and genetic risks. Current nutritional and genetic epidemiological methods yield 'risk factors' derived from population studies. These risk factors are statistical estimates of the percentage reduction in disease in the population, if the risk were to be avoided or the gene variant was absent. Developing individual risk factors considering the genetic diversity of human populations, the complexity of foods, cultures and lifestyles, and the variety of metabolic processes poses enormous challenges for personalizing dietary advice.

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