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Thursday, April 2, 2009

Nutrigenomics

Nutrigenomics is the study of molecular relationships between nutrition and the response of genes, with the aim of extrapolating how such subtle changes can affect human health. Nutrigenomics focuses on the effect of nutrients on the genome, epigenome, proteome, and metabolome. By determining the mechanism of the effects of nutrients or the effects of a nutritional regime, Nutrigenomics tries to define the relationship between these specific nutrients and specific nutrient regimes (diets) on human health. Nutrigenomics has been associated with the idea of personalized nutrition based on genotype. While there is hope that nutrigenomics will ultimately enable such personalised dietary advice, it is a science still in its infancy and its contribution to public health over the next decade is thought to be minor.


Definitions

Nutrigenomics focuses on the effect of nutrients on the genome, proteome, and metabolome. It is applying the sciences of genomics, transcriptomics, proteomics and metabolomics to human nutrition in order to understand the relationship between nutrition and health. Nutrigenomics is a new science and has several different definitions. Nutrigenomics has been defined as the application of high-throughput genomic tools in nutrition research. The term high throughput tools in nutrigenomics refers to genetic tools that enable literally millions of genetic screening tests to be conducted at a single time. When such high throughput screening is applied in nutrition research, it allows the examination of how nutrients affect the thousands of genes present in the human genome. Nutrigenomics involves the characterization of gene products and the physiological function and interactions of these products. This includes how nutrients impact on the production and action of specific gene products and how these proteins in turn affect the response to nutrients.


Background and preventive health

Throughout the 20th century, nutritional science focused on finding vitamins and minerals, defining their use and preventing the deficiency diseases that they caused. As the nutrition related health problems of the developed world shifted to overnutrition, obesity and type two diabetes, the focus of modern medicine and of nutritional science changed accordingly.

In order to address the increasing incidence of these diet-related-diseases, the role of diet and nutrition has been and continues to be extensively studied. To prevent the development of disease, nutrition research is investigating how nutrition can optimize and maintain cellular, tissue, organ and whole body homeostasis. This requires understanding how nutrients act at the molecular level. This involves a multitude of nutrient-related interactions at the gene, protein and metabolic levels. As a result, nutrition research has shifted from epidemiology and physiology to molecular biology and genetics and nutrigenomics was born.

The emergence and development of nutrigenomics has been possible due to powerful developments in genetic research. Inter-individual differences in genetics, or genetic variability, which have an effect on metabolism and on phenotypes were recognized early in nutrition research, and such phenotypes were described. With the progress in genetics, biochemical disorders with a high nutritional relevance were linked to a genetic origin. Genetic disorders which cause pathological effects were described. Such genetic disorders include the polymorphism in the gene for the hormone Leptin which results in gross obesity. Other gene polymorphisms were described with consequences for human nutrition. The folate metabolism is a good example, where a common polymorphism exists for the gene that encodes the methylene-tetrahydro-folate reductase (MTHFR).

It was realized however, that there are possibly thousands of other gene polymorphisms which may result in minor deviations in nutritional biochemistry, where only marginal or additive effects would result from these deviations. The tools to study the physiological impact were not available at the time and are only now becoming available enabling the development of nutrigenomics. Such tools include those that measure the transcriptome - DNA microarray, Exon array, Tiling arrays, single nucleotide polymorphism arrays and genotyping. Tools that measure the proteome are less developed. These include methods based on gel electrophoresis, chromatography and mass spectrometry. Finally the tools that measure the metabolome are also less developed and include methods based on nuclear magnetic resonance imaging and mass spectrometry often in combination with gas and liquid chromatography.


Rationale and aims of nutrigenomics

In nutrigenomics, nutrients are seen as signals that tell a specific cell in the body about the diet. The nutrients are detected by a sensor system in the cell. Such a sensory system works like sensory ecology whereby the cell obtains information through the signal, the nutrient, about its environment, which is the diet. The sensory system that interprets information from nutrients about the dietary environment include transcription factors together with many additional proteins. Once the nutrient interacts with such a sensory system, it changes gene, protein expression and metabolite production in accordance with the level of nutrient it senses. As a result, different diets should elicit different patterns of gene and protein expression and metabolite production. Nutrigenomics seeks to describe the patterns of these effects which have been referred to as dietary signatures. Such dietary signatures are examined in specific cells, tissues and organisms and in this way the manner by which nutrition influences homeostasis is investigated. Genes which are affected by differing levels of nutrients need first to be identified and then their regulation is studied. Differences in this regulation as a result of differences in genes between individuals are also studied.

It is hoped that by building up knowledge in this area, nutrigenomics will promote an increased understanding of how nutrition influences metabolic pathways and homeostatic control, which will then be used to prevent the development of chronic diet related diseases such as obesity and type two diabetes. Part of the approach of nutrigenomics involves finding markers of the early phase of diet related diseases; this is the phase at which intervention with nutrition can return the patient to health. As nutrigenomics seeks to understand the effect of different genetic predispositions in the development of such diseases, once a marker has been found and measured in an individual, the extent to which they are susceptible to the development of that disease will be quantified and personalized dietary recommendation can be given for that person.

The aims of nutrigenomics also includes being able to demonstrate the effect of bioactive food compounds on health and the effect of health foods on health, which should lead to the development of functional foods that will keep people healthy according to their individual needs.

Nutrigenomics is a rapidly emerging science still in its beginning stages. It is uncertain whether the tools to study protein expression and metabolite production have been developed to the point as to enable efficient and reliable measurements. Also once such research has been achieved, it will need to be integrated together in order to produce results and dietary recommendations. All of these technologies are still in the process of development.



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