Science Blog #3 - Nutrigenomics – Best diet for our genes

India once notorious for being a begging bowl is now more with swollen tummies. This evolution from under to over nutrition emphasizes diet and exercise as need of the hour. Human nutrition got evolved from ‘naturalistic era’, where Hippocrates mentioned let food be thy medicine to the current ‘cellular era’ where role of each nutrient’s effect on genome and metabolic pathways is relevant in disease prevention. In a lay man’s perspective when we compare or get puzzled out why only few are more prone to lifestyle disorders more than others even though the diet remaining same? and here comes the need for looking into DNA for advice.

The concept of diet influence health is known to us from 4000BC but with the revolution in molecular genetics in the late twentieth century, scientists set out to identify genes that interact with dietary components. Throughout this cellular era (20th century), nutritionists focused on finding gene-diet interfaces to understand How to rightly eat for our DNA. The shift in diet pattern from coarse to refined grains in our country as part of globalization or we say ‘mall culture’ kicked off various diseases like obesity, cardio vascular diseases, type-II diabetes commonly dubbed as diseases of civilization. India has reached its pinnacle in terms of highest rates of Coronary Heart Disease (CHD) in the world with thrice prevalence in urban compared to rural (Fig. 1). Obesity (Fig. 2a and b) and diabetes (Fig. 3) have also increased dramatically in urban areas and in high-income rural residences (Sinha et al. 2003). Obesity is also related to several other chronic diseases, including type-2 diabetes, hypertension, cardiovascular diseases, various types of cancers and psychosocial problems.

Fig 1. Estimated mortality from coronary heart disease. Source: Trehan 2006

Fig 2. a. Projected prevalence of overweight males in India aged 30 years or more, 2005 and 2015. b Projected prevalence of overweight females in India aged 30 years or more, 2005 and 2015. Source: WHO Report

Fig. 3 Estimated number of Diabetic subjects in India. Source: Mohan et al. 2007a, b

To tackle these diseases, it’s important to understand how nutrients act at the molecular level which in turn involves a multitude of nutrient-related interactions at the gene, protein and metabolic levels in humans. As a result, nutrition research shifted from Epidemiology and Physiology to Molecular Biology and Genetics and “nutrigenomics” was born. Nutrigenomics is a logical extension of biotechnology, it also includes how nutrient interact with plant genome resulting its productivity and quality into human diet, which can affect health.

The conceptual basis for this new branch of genomic research can best be summarized by the following six tenets of nutrigenomics:

• Under certain circumstances and in some individuals, diet can be a serious risk factor for a number of diseases.
• Common dietary chemicals can act on the human genome, either directly or indirectly, to alter gene expression or structure.
• The degree to which diet influences the balance between healthy and disease states may depend on an individual's genetic makeup.
• Some diet-regulated genes (and their normal, common variants) are likely to play a role in the onset, incidence, progression, and/or severity of chronic diseases.
• Dietary intervention based on knowledge of nutritional requirement, nutritional status, and genotype (i.e., "personalized nutrition") can be used to prevent, mitigate or cure chronic disease (11).
• Plants produce being major source of diet, understanding the nutrient-genome interface will definitely help to improve the quality of diet, resulting better health

The concept of personalized nutrition or medicine is in infancy we agree, but there is immense potential in this field unraveling the key factors that affect plant as well as human health. Often we get confused by jargons like nutrigenomics and nutrigenetics. Jose M. Ordovas, a pioneer researcher in this field explains that ‘Nutritional genomics covers nutrigenomics, which explores the effects of nutrients on the genome, proteome and metabolome, and nutrigenetics, the major goal of which is to elucidate the effect of genetic variation on the interaction between diet and disease (12).

It is an emerging field that tends to unfold the role of nutrition on gene expression which brings together various merging platforms like genetics, molecular biology, bioinformatics, bio computation, physiology, pathology, nutrition, sociology and ethics.

Fig 1. Holistic approach of various platforms for nutrigenomics

To unravel the mystery of various chronic diseases, nutrigenomics is blooming in many parts of the world including India. Till now studies have been mainly focused on single nucleotide polymorphisms (SNPs) Mitra et al. 2005 and its associated diseases (Cancer, Obesity, Diabetes, Cardio Vascular Diseases (CVD), Neural Tube Defect (NTD), Leukemia, Down syndrome, Spina bifida) and have also emphasized the interaction between folate nutrition and folate-dependent enzyme polymorphism (folate nutrigenomics) (Fig. 4). Ghodke et al. 2011 also profiled SNPs across intracellular folate metabolic pathway in healthy Indians. The role of folate, vitamin B12 and homocysteine levels in acute lymphoblastic leukemia, suggest that gene-environment interaction may be an important factor in the development of acute lymphoblastic leukemia (13). A part of the approach, 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 (14-17). Gene-diet interaction studies revealed that the adiponectin gene polymorphism contributed to insulin resistance and diabetes and this was exaggerated in those consuming diets with higher glycemic loads (18).

Fig. 4 Single Nucleotide Polymorphism, its associated gene alteration and diseases. Source: Modified from Mitra et al. (2005)

Studies till now majorly only focussed on diet-gene interaction, but its equally relevant to unravel how the type of nutrient as well as its uptake affect plant produce which are part of our diet and this laccuna have to be adressed by plant biologists. Phenotypic variation of the majority of agronomically important crop traits are under polygenic control and understanding the genetic and molecular basis of the natural variation within and between populations will be essential for connecting genes and alleles to phenotypes. Understanding the molecular genetic basis of metabolic traits in agricultural seed crops that are essential for nutrition in humans and animals is a key component of meeting future global food and feed needs is an area of nutrigenomic research (Fig 5).

Fig 5. Nutrigenomic approach model

As more gene-diet association are reporting, genetic profiling, nutritional prescriptions and thus nutrigenomics are expected to become a common place and certainly the wave of the future. Despite the tremendous potential in plant and human health, the complexity associated with the field also drives much ethical concerns. Addressing the genetics and nutritional genomics knowledge gap will help in eradicating the social issues, create more awareness, confidence and trust among the public. Public concerns over nutrigenomics are relevant to science and to the food industry. Past and present food scares, such as genetically modified, demonstrate the importance of addressing public concerns sooner rather than later, and of taking the social issues around science as seriously as technical ones. Recent surveys have shown a wider acceptance of nutrigenomic research in both plant and animal science and hoping that it wont get a consumer backlash like genetically modified goods in India. Regulation is necessary both to ensure responsible use of research and to assure the public that products can be trusted. Manufacturers need regulation and public engagement both for the guidance they provide and to demonstrate a will to improve the safety, reliability and health benefits of their products Sherwood (20). Therefore there is an urgent need to boost more research in this field to help people in understanding the relationship between plant physiology, diet and human health, and to ensure that everyone benefits from this genomic revolution. Public awareness on nutritional requirement for diet related diseases is very critical and hence dietary guidelines and genome policies have to be familiarized among public. We should be aware that the genes we inherit cannot be altered while, the changes in the dietary pattern can help us to get desired results.
Since 2002 studies on diseases related to insufficient diet, lack of physical activity and changing lifestyles were conducted but mostly were not much correlated with the genetic make up. Thus, more research work will enhance consumer confidence, awareness and a better future with personalized nutrition to get away from non communicable diseases. Hence, the early identification of at-risk individuals and appropriate intervention in the form of weight reduction, changes in dietary habits and increased physical activity could greatly help to prevent, or at least delay the onset of dietary disorders in India. The ultimate aim of this emerging field of science is prevention than cure which will answer us how to eat for our DNA.

It's a need of the hour as to how nutrients affect our genes and this article entails that.

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