Nutrigenomics: Challenges and Opportunities

Abstract

Nutritional genomics is one of the emerging fields of food sciences for innovative trends in food sciences. Understanding of the genetics of the human health and diseases is very important to set the diet and nutrition plans. Functional genomics studies have paved the path to the cure of the disease with diet. With the advancement in the field of genetics and genomics especially next generation sequencing and molecular markers, nutrigenomics has been gaining much attention in the field of food sciences. The chapter will elaborate challenges and opportunities associated with the field of nutrigenomics and will propose strategies to address the issues.

1. Introduction

Nutrigenomics is a discipline of nutrition that uses molecular approaches to discover, access, and understand the varied reactions produced by a certain diet in individuals or communities. Its goal is to figure out how the components of a certain diet (bioactive chemical) affect gene expression, which might have increased or decreased its potential [1].

Nutritional genomics (or nutrigenomics) as the field of study that studies all forms of interactions between food and the genome and is characterized by the use of high-throughput genomic (or genome related) methods. Nutritional genetics (also known as nutrigenetics) is a branch of nutrigenomics that studies how genomic variants interact with dietary variables and the consequences of these interactions [2].

Nutrigenomics is used to integrate genetic methods into nutrition studies. Nutrigenomics (also known as nutritional genomics) is the study of the connections between meals or dietary supplements and an individual’s genome, as well as the phenotypic impacts of these interactions [3].

2. Basics of nutrigenomics

Diet play an important role on the health of human. However nutrigenomics is the interaction of food-gene interactions, sometimes known as ‘inborn errors of metabolism,’ which have long been corrected by dietary changes [4] (Figure 1). Nutrigenomics is a relatively recent science that explains how some foods affect your DNA. What you eat has a direct impact on the genetic messages your body receives. It is significantly change how food interacts with your body, reduce weight, and enhance your health if you can learn the language of your genes and regulate the messages and instructions they provide your body and metabolism.” The study of the impact of nutrition on the genome, proteome, and metabolome is known as nutrigenomics [5].

Figure 1.

Interaction of nutrient and gene.

Nutrigenomics tries to determine the impacts of various nutrients on the genome, including macronutrients and micronutrients, and investigates the interactions between genes and nutrients or food bio-actives, as well as their consequences on human health. Nutrigenomics is the study of the effects of nutrition on transcription varied responses of genomic variations and gene expression. Nutrigenomics deals with study of a biological system using functional genomic methods in order to learn how dietary components alter metabolic pathways as well as homeostatic control [6]. Nutrigenetics will provide crucial information to help clinicians decide the ideal food for a specific person, i.e. individualized diet. Nutrigenomics research employs tools such as transcriptomic, proteomics, and metabolomics. Nutrition has been shown to alter expression of genes on numerous levels, chromatin structure, including gene function, signal transduction and protein function [5]. Food intake has been linked to the prevalence and severity of chronic diseases. Type 2 diabetes, obesity, metabolic syndromes, cardiovascular disease, and some kind of cancer are among the many nutrition-related illnesses that are polygenic and multifactorial, with onset and the progression linked to several s genes variations, as well as a variety of environmental factors, including diet [7].

Nutrigenomics is a new and emerging discipline of genomics that studies the impact of dietary consumption on the whole genome (full genetic make-up, including epigenetic modifications), proteome is the total number of proteins, and metabolome is the whole number of molecules in the body and the sum of all metabolites. Galactosemia, for example, is a disease caused by an inherited genetic deficit in one of the three enzymes involved in galactose processing [8].

3. Genomics: a molecular approach

Functional genomics technologies like metabolomics, transcriptomics and proteomics have a few things in common. For starters, they are non-targeted, all-encompassing technology. Second, they rely on determining the actual concentrations of a single type of biomolecule’s entire set for example protein, mRNA or metabolite. Finally, they associate the entire collection of particular type of biomolecule (transcriptomes, proteomes, or metabolomes) under various environmental situations [9].

Above discuss technologies has different purpose. When investigating the biological effects of functional food bio actives, for example, a transcriptomics technique appears the most suited since it provides a comprehensive overview of a cell’s reaction to a bioactive that can be compared to known “healthy” or “unhealthy” responses. A metabolomics method is very useful in metabolic engineering because the metabolome is the closest to the product/phenotype under examination [9]. The fundamental benefit of an applied genomics method is that it allows scientists for the first time to get a comprehensive understanding of the biological activities that happen in cells in response to specific therapies. We will obtain a greater knowledge of these processes, allowing us to direct them in the right direction for example, by slowing down or even inhibiting disease development. Obtaining massive amounts of data is no longer a problem, but interpreting that data (converting data into knowledge) remains a substantial bottleneck. This is due in part to the fact that a large number of genes have yet to be assigned a function, making biological data interpretation on these genes challenging. Additional, and perhaps the most pressing issue at the moment, is that researchers in the life sciences have never been taught how to deal with vast volumes of data and interpret them holistically, but have instead been taught to employ a reductionist approach. Recognizing this constraint, on the other hand, is the first step toward finding a solution [10].

3.1 Transcriptomics

Transcriptomics is the study of the entire set of RNA transcripts that have been activated. Because mRNAs are synthesized at a specific time, in specific tissue of a specific organism, expression of gene changes depending on the conditions and time periods [11]. When activated, transcription factors travel toward nucleus and attach to a particular DNA sequence found in the promoter region of genes, where they block or facilitate transcription [12]. Transcriptomics can help to provide data of mechanisms or underlying impacts of a certain nutrient or diet in nutrition studies. It help in recognizing and characterizing the pathways controlled through bioactive compounds and nutrients in foods, as well as it identify the metabolites, genes and proteins that modify as predeceases progress [1].

3.2 Proteomics

Proteomics is the molecular approach is used to investigate the entire form of proteins complex in a species biological activities. These proteins function normally in the tissue, organ, and cell but in particular biological conditions, such as transcriptome, and they can change their activity and the level of gene expression. Proteins are a type of molecule that can be found in every living cell [13]. They have structural, transport, biochemical, cell signaling, mechanical and storage functions in the cell. They’re also a necessary component of the human diet. The amount of proteins made by an organism is higher as compared to the number of genes it has. This occurs as a result of many posttranslational and translational changes [14]. Proteomics is the study of protein expression using a variety of technologies. It does so by employing techniques like chromatographic electrophoresis, prefractionation of samples using extraction sequences, and organellar proteome analysis, among others. As a result, Proteomics is a critical resource for Nutrigenomics, as it establishes a connection between genome sequences and cell behavior, and acts as a biological tool for understanding the process of genetic function assessment, as well as how the genome is activated in response to a certain diet. The butyrate activities change the expression of many proteins in the ubiquitin-proteasome system. Butyrate modulates essential proteins involved in the process of apoptosis, cell differentiation and cell cycle [1].

3.3 Metabolomics

The metabolome of an organism or species is made up of a collection of tiny secondary and primary metabolites as well as bodily fluids. Metabolomics is a branch of functional genomics that analyses metabolite alterations with the goal of isolating and characterizing them. Advances in this field may make it easier to comprehend how a person’s genotype influences his or her phenotype [15]. Metabolomics has various nutritional uses, one of which is to determine the patterns and metabolic problems induced by a human food, as well as how these changes may affect the health or sickness of human As a result, metabolomics analyses metabolism in the context of genetic and environmental disturbances, which may be examined and interpreted using bioinformatics and statistical methods [16]. Small chemical substances that directly interact with proteins and other macromolecules and are dissolved in the cell cytoplasm are referred to as metabolites. There are two types of metabolites: main and secondary. Primary metabolites are directly engaged in macromolecule synthesis and breakdown, whereas secondary metabolites are more abundant in plants and serve as an important compound and defense mechanisms [17]. In the field of nutrition, metabolomics enables researchers to better understand metabolic instabilities and arrangements that are caused or exacerbated by diet. This advances our understanding of how an individual’s health/illness is affected by an extra or absence of certain nutrient or molecules (secondary metabolites) contained in food. These chemicals (nutrients or not) interact with the body in a variety of ways, altering metabolome pathways. Perilla alcohol (a monoterpene derived from strawberries) can, for example, act as an anticancer molecule when exposed to particular chemical stimuli [1].

4. Diet-gene-disease triangle

Dietary substances can have a direct or indirect effect on gene expression. Nutrients could act as molecules for transcription factor sites or to be digested via primary or secondary biosynthetic processes at the cellular level, changing substrate or intermediate quantities and so favorably or unfavorably modulating signal pathways. Among the most essential molecules involved in nutrient-induced gene activity is transcription factors (TFs). The PPARs TFs, which include 48 individuals in the genetic material, are among the most important groups of nutrition sensors [18]. The preponderance of sensors in this family connect nutrients and their metabolites, as well as regulate gene expression in fatty acid gluconeogenesis, amino acid metabolism, oxidation, ketogenesis, cellular proliferation and the acute-phase response of the liver. PPAR-ligands include the fatty acids arachidonic acid (20:4n6), palmitic (16:0), linoleic (18:2n6) and oleic (18,1n9), as well as the 8- (S) hydroxyeicosatraenoic acid, eicosanoids 15deoxy-12 and 14prostaglandinJ2. Fatty acid sensors are provided by these nuclear receptors. Hyperforin binds to nuclear receptors directly and regulates genes. Lipid sensors typically form heterodimers with retinoid receptors, which have a ligand derived from vitamin A, another dietary nutrient [10].

The liver X receptor binds to certain nucleotide sequences (response elements) in the promoter regions of numerous genes as heteromers. In response to ligand engagement, nuclear receptors change their shape, allowing corepressors to dissociate and coactivator proteins to connect in preparation for transcriptional activation. The key metabolic condition activates a variety of genes, such as those implicated in fatty acid oxidation & storage. These TFs operate as nutrition sensors in metabolically active organs like the liver, stomach, as well as adipose tissue via changing the degree of DNA transcription of particular genes in response to food changes [3]. Some TFs are regulated indirectly by dietary substances. Protease cleavage, for example, activates sterol regulatory element binding proteins (SREBPs), minimal quantities of oxy sterols, insulin/glucose, and polyunsaturated fatty acids govern this process. High glucose levels activate the carbohydrate-responsive element-binding protein (chREBP), which is controlled via reversible phosphorylation mechanisms. The DNA-binding protein regulates the expression of lipogenic genes. Furthermore, dietary substances have the ability to influence signal transduction pathways directly. Green tea, for example, includes the polyphenol 11-epigallocatechin-3-gallate (EGCG), which inhibits tyrosine phosphorylation of the Her-2/neu receptor and the epidermal growth factor receptor, reducing signaling via the PI-3-AKt kinase-NF-kB pathway. The stimulation of the NF-kB cascade has indeed been associated toward certain types of breast cancer [4].

Other nutrients, including such polyunsaturated fatty acids (PUFAs) like n-3 and n-6, often known as omega-3 and omega-6 fatty acids, were shown to influence gene expression. Several proteins gene expression are involved in lipid and glucose metabolism has been found to be affected by PUFA ingestion in animal studies. There has also been evidence of a link between the PPARA Lue162Val polymorphism and n-6 PUFA intake. In those who hold the less common V162 allele, increased n-6 PUFA intake is connected to a considerable decline in triacylglycerol concentration, though not in people who carry the L162 variety. Conversely, n-3 PUFA consumption reduces triacylglycerol concentrations in L162 and V162 carriers. In the human diet, approximately 40 micronutrients are required. CVD has been linked to inadequate intakes of key micronutrients. Nutrient deficiencies are much more important than radiation due to the obvious regularity of exposure to an environment that causes DNA damage. The large presence of uracil in human DNA (4 million uracil/cell) causes chromosomal disruption in folate deprivation. Nutrients like folate, carotenoids, Vitamin D, B6, B12 helpful for the management of cancer, neural tube abnormalities. These nutrients help in Hyperhomocysteinemia that is major risk for cardiac disease. Vitamin B12, niacin, folic acid, vitamin C, vitamin E, zinc, iron and B6 deficiency appears to damage DNA in the same way that radiation does, causing single and double-strand breaks, oxidative lesions, or both [10].

Amino acids can act as dietary signals by modulating the expression of specific genes. Cells have been shown to detect variations in amino acid levels and respond through mechanisms such as transcription control, mRNA stability, and up or down regulation of translation start. Blood glucose levels are influenced differently by simple and complex carbohydrates. High glycemic index (GI) food produce more insulin while producing fewer insulin receptors. Several genes involved in the glycolytic and lipogenic pathways are transcribed when blood glucose levels are high. Food-regulated genes must be implicated in the beginning, progression, and severity of disease since dietary components are regularly eaten and are involved in the control of gene expression both indirectly and directly [7].

5. Life style associated metabolic diseases

The main factor related with today’s lifestyle is unhealthy living habits. It is culminating in diseases with high mortality rates, particularly chronic diseases, which are responsible for the majority of fatalities over the last decade. Lifestyle-related diseases are a set of diseases caused by humankind’s long-term exposure to bad diet, lifestyle, and living conditions. Cardiac, renal failure, nutrition-induced malignancies, hypertension, diabetes, chronic bronchitis and other diseases have nearly identical risk factors because they are slow-progressing, non-infectious, and non-transmissible. The primary motivation for choosing lifestyle-related disorders for this assessment is their impact on human health. According to the WHO research, illness profiles have shifted rapidly from communicable to non-communicable diseases during the last few decades, regardless of area, race, or economic status. Around 60% of deaths globally were due to lifestyle-related chronic diseases, which were twice as common as infectious diseases. Non communicable diseases were also responsible for 53 percent of deaths in India, with cardiovascular disease accounting for 24 percent of all deaths (CVDs). These disorders, like epidemiological characteristics, have particular metabolic risk factors related with physiological mechanisms that result in mitochondrial changes, oxidative stress, and inflammation. These reactions to changes in the environment play an important role in the onset and progression of lifestyle disorders. The increase in metabolic risk factors of blood such as blood pressure, glucose, lipids, and other variables is primarily due to a poor diet. Inflammation in the human body is also affected by diseases related with modern lifestyles. Eicosanoids (arachidonic, eicosapentaenoic and docosahexaenoic acid), a fatty acid metabolite, regulate the inflammation process. Inflammation has been linked to a poor diet and the current social and environmental stressors that humans encounter. In an animal model, scientists discovered the genes (plasminogen activator inhibitor-1 linked with fat) that were responsible for the change. Changes in lifestyle and environment have an impact on not just human metabolic and physiology processes, but also the intestinal microbiome, which can lead to health issues. The idea that these diseases are only found in rich countries has been debunked, as low- and middle-income countries have more favorable social, economic, and environmental conditions for their development. If this change continues, illness profiles will worsen, especially in developing and underdeveloped countries [19].

6. Nutrigenomics and chronic diseases

Nutrition is the act of providing various constituents to the organism. Nutrients play important functions carbohydrates and fats are the source of energy, for the structure of cell protein is the best sources, vitamins and minerals is good for the control of metabolism, allowing the organism to maintain its homeostasis. The combination of different factors, like social state, emotional, physical activity and genetic background, determines an individual’s nutritional status [20]. Diet plays an important role because the minerals and other bioactive chemicals found in food can either be healthy or cause a variety of disorders. Many chronic disease like phenylketonuria, cancer, diabetes, and dyslipidemias, are among the disorders linked to food consumption. In this approach, a person’s health will be determined by the interaction of their genes and their dietary habits. As a result, nutrigenomics, like other omic sciences, aims to better understand the relationship among genes and diet (nutrients) [21].

6.1 Obesity

Obesity is the common problem now days different factors are responsible like environmental, genetic factors, lifestyle and metabolic syndromes. Genetic variables account for 80 percent of the variance in body mass index (BMI) between twins. Because obesity generates a persistent inflammatory response, using Nutrigenomics to control it is extremely promising. In food bioactive compounds are present like in olive oils tyrosol present, in fruits and greeneries quercetin present and in tomatoes lycopene is present etc. [22].

Food-derived bioactive chemicals can also interfere with genes in different ways. One of the principal pathways for the expression of gene modification is during transcription, when inflammatory mediators are synthesized, which plays a key role in a variety of chronic diseases, including obesity. Interleukin-1 is one of these mediators, and it induces the creation of numerous other molecules during the inflammatory cascade after it is activated. Green tea bioactive ingredient tocopherol works as an anti-inflammatory [12].

6.2 Cancer

Different factors are responsible for cancer like age, genetic, lifestyle, physical activity, and diet. Due to deficiencies of nutrients like vitamins E, C, B12, as folic acid, vitamin B6, C, and as well as zinc, selenium and niacin, have previously been found to cause change in DNA similar to those seen after contact to radiation. These changes can result in double-strand DNA breakage and oxidative damage. They were also found to be closely linked to the growth of cancer. Contaminated food produce harmful metabolites that regulate the gene expression [13].

Mutation has the potential to cause serious liver problems such cancer, necrosis and cirrhosis. During metabolism of folate, folic acid in food is absorbed by the intestine and converted into 5-methyltetrahydrofolate by a series of chemical catabolism and synthesis processes. 5-methyltetrahydrofolate component is required for the production of methionine, which is employed in the DNA mutilation process. Therefore, a low-folic acid diet can disrupt this process and also interfere with the replication of DNA, increasing the risk of cancer formation. Nonetheless, many minerals defend against the development of cancer [23]. Selenium stimulates the production of glutathione peroxidase, an enzyme that reduces hydrogen peroxide and maintains the integrity of cell membranes and zinc which also influences processes such as apoptosis genomic stability modulation and genetic expression [24].

6.3 Diabetes

Around 90% of people in world suffer from diabetes. Type 2 diabetes is a complex disease that is caused by a combination of hereditary and environmental factors. There are Single-nucleotide polymorphism SNPs linked to the likelihood of acquiring type 2 diabetes. Tests for the detection of SNPs linked to Type II Diabetes became available to the general public as genome sequencing and decoding progressed. During these tests, the patient might find out if he or she has a genetic predisposition to developing the condition. Due to low food income and insulin tolerance, some people got diabetes later in life. Patients who had a positive result for the existence of type II diabetes changed their lifestyles, particularly their eating habits, which later reduced the disease’s progression in this group [1].

6.4 Cardiovascular

CVD is defined by the creation of intimal lesions in the blood arteries as a result of fibrosis, lipid buildup, inflammatory response, and cell death. According to a WHO report, cardiovascular disease is the leading cause of death. Global estimates put the death toll at 17.5 million in 2012, representing for 31% among all deaths. In the treatment and prevention of cardiovascular disease, diet is essential. Changes in diet can protect genes involved in lipid metabolism and synthesis, such as arachidonate 5-lipoxygenase (ALOX5), apolipoprotein E (APOE), fatty acid synthase (FASN), and peroxisome proliferator activated receptors (PPARs), lipoprotein lipase (LPL), and others. The 28.1-kDa protein apolipoprotein (APOA1) is important for bodily disposal and is a form of high lipoprotein (HDL). This gene is used as a biomarker to diagnose cardiovascular illnesses like myocardial infarction in the early stages. As a result, HDL clearance from plasma is necessary while eating a low-fat diet. PUFAs play a key function in influencing the expression of factors involved in glucose and lipid metabolism [25]. Fatty acids helps individuals lower their LDL cholesterol levels. Lipoxygenase, also known as arachidonate 5-lipoxigenase (5-LOX), is an important enzyme that controls the production of leukotrienes, inflammatory cytokines, and chemokines. Its expression is increased in atherosclerotic lesions, causing more inflammatory cells to be mobilized. Endothelial nitric oxide synthase in blood arteries converts L-arginine to nitric oxide (NO). By activating the guanylyl cyclase receptor and boosting cGMP levels, NO migration into vascular smooth cells devalues blood cells. It also works as a leukotriene and platelet aggregation inhibitor, lowering the risk of white blood cell adhesion and atherosclerosis. Increased eNOS expression has been linked to the creation of H2O2 and has been linked to endothelial dysfunction, which leads to CVD. In both animals and humans, L-arginine has been demonstrated to be useful in the treatment of hypercholesterolemia. Omega three polyunsaturated fatty acids increase eNOS expression, resulting in vasorelaxation, while lowering circulating indicators such as E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 (VCAMs- 11) [26].

6.5 Cholesterol

The endothelium and leukocytes interact through the vascular cell adhesion molecule-1 (VCAM-1). During the start of atherosclerosis VCAM-1 binds monocytes and T lymphocytes, resulting in plaque development. However, proinflammatory cytokines such as tumor necrosis factor- (TNF-) and interleukin-1 generate oxidized lipids necessary for VCAM-1 expression (IL-1) [19].

6.6 Inflammation

The inflammatory process is known to be influenced by the nutritional composition of diet systems resulting in immune response regulation, via altering gene expression as well as interfering with signaling cascade. Inflammation is the body’s biological response to any invasion or injury, and it can be acute (short-term self-healing) or chronic (long-term). Inflammation later in life might linger for many years, leading to a variety of disorders such as cancer, intestinal allergies, atherosclerosis, and so on [23]. The immune system regulates the inflammatory process, and numerous immunological mediators play a key role. The famous spice curcuma longa (turmeric) has long been used in Ayurvedic medicine to treat inflammation. It includes a variety of bioactive chemicals, but ‘curcumin’ is one of the most important metabolites, accounting for a wide range of pharmacological actions including antioxidant, antibacterial, and anti-inflammatory effects. There is evidence that curcumin is a greatly pleiotropic chemical having potential to interact with inflammatory molecular targets. This was discovered as promising helpful not just for inflammatory diseases, but also for some tumors. Curcumin play an important role in the activity of H+, K + -ATPase and it also decreased the histone H3 acetylation, which hindered the expression of gene (H+, K + -ATPase). It regulates the production of cytokine signaling-1 (SOCS-1 and 3) and p38 MAPK suppressors, which suppress the expression of LPS-induced inflammatory mediators such as IL-6, TNF-_, and COX-2 mRNAs in macrophages. LPS-induced SOCS-1 and -3 expression as well as p38 MAPK kinase activation are reduced when nuclear translocation is altered further. TNF-_ activity and production are reduced in vitro, in vivo, and in people when curcumin (diferyloylmethane) is taken orally, according to bioavailability and safety studies. Vitamin A supplementation has been shown to help with a variety of inflammatory illnesses, including skin disorders and precancerous and cancerous situations. Retinoid, a vitamin A derivative, has been shown to prevent tumors growth and boost the immune system (Table 1) [19].

Nutrients	Gene	Diseases	Reference
Curcumin	H+, K + - ATPase	Help in the treatment of gastric ulcers	[27]
	IL-6,TNF-_, COX2	Reduces inflammation	[28]
	SOCS1–3,p38MAPK	Trans locates nuclear material in a different way.
	TLRs & MyD88	Infection with Helicobacter pylori has an anti-inflammatory impact.	[29]
Retinoic Acid	TLR4/NF-kappa B	It helps to minimize mastitis irritation.	[30]
Vitamin E	CRP, IL-8, PAI_1	Arthrosclerosis	[31]
Sesamol	MCP-1, RANTES, IL-1_, IL-6, and CXCL-16	Reduce the number of lesions caused by arthrosclerosis.	[32]
	ABCA1, ABCA2, APO2, LCAY, CYP7AI, APOE,	Help in cholesterol metabolism and transportation	[32]
Vitamin B6	TNF_,, COX-2, iNOS and IL-6, IFN-_	Help in the inflammatory bowel diseases	[33]
Grains, legumes and refined rice	APOA5 c.-1131CNT and triglyceride and APOA-V	Diabetes type 2	[34]
Polymorphisms	APOA5	Uyghur	[35]
polymorphism	Triglycerides and the APOA5 c.-1131TNC,	Age-related association in mice	[35]
	APOC3 (rs5128)	Metabolic syndrome	[36]
	1β (PGC-1β), a co-activator of PPARγ	It reacts to changes in the macronutrient content of the food.	[37]
Selenoproteins	DIO1, SEPHS1, DIO2, GPX1, TXNRD2, GPX3 and SEPSECS	Crohn’s disease	[38]
Zinc	ZNF365	Low zinc levels	[39]
Eicosapentaenoic acid	omega-3 (n − 3) fatty acids are docosahexaenoic acid (DHA) the long chain polyunsaturated	Inflammation	[40]
Vitamin D	NOD2	Crohn’s disease	[41]
Flavonoids and carotenoids	ω − 3 fatty acids	Gene expression and oxidative stress production of inflammatory mediators	[42]
Gluten	HLA-DQ (DQ2 and/or DQ8)	Coeliac disease	[43]
SNPs.	SNPs	Obesity, diabetes, cancers, cardiovascular disease and brain disorders	[44]
Avian responses to nutrition	IGF1 and lysine (K)-specific histone demethylase 5A (KDM5A)	Growth and epigenetic regulation of genes	[45]
Vitamin D	Retinoic acid receptor (RAR) binds	Nutritional imbalances have been linked to aging, behavioral problems, chronic fatigue, cardiovascular disease (CVD), diabetes, neurological disorders, cancer, immunological diseases, stroke, multiple sclerosis, Parkinson’s disease.	[46]
Folate-related enzyme	677C → T	Hyperhomocysteinemia	[47]
SNPs	Glucose-6-phosphate dehydrogenize (G6PD) gene, Phenylalanine hydroxylase gene and galactose-1-phosphate uridyltransferase (GALT) gene	Prevent from disease Phenylketonuria (PKU), Favism and Galactosemia,	[48, 49]
Selenium	Selenium-dependent Enzyme	Lung cancer	[50]

Table 1.

Nutrients gene interaction for the management of disease.

7. Nutrigenomics approach to functional food

Because of their interaction with diseases, nutrition and health are at the forefront of the scientific community, paving the way for the development of health-promoting food prototypes (s). Functional food is any food or food component that is beneficial for health and also provide essential nutrients. Functional component derived from plant like omega 3 fatty acid, antioxidant, vitamin, protein, dietary fibers, amino acid, flavonoids and prebiotics these compound help in the management of lifestyle related disease. Curcumin, a dietary flavonoid, inhibited adipogenesis in pre-adipocytes from humans. Curcumin reduce hyperglycemia and increase insulin sensitivity while also lowering TNF- levels. Oral treatment of Trigonella foenum graecum seed extract reduce the triglycerides, blood glucose, total cholesterol and increase high density lipoprotein. Due to presence of bioactive compound like 4-hydroxyisoleucine (amino acid) and the steroid saponin trigonelline fenugreek seed powder has hypoglycemic properties [51]. Functional compound has best therapy for the lifestyle related diseases. Similarly, omega-3 fatty acids DHA and EPA generated from the oil of fish have an important role in a variety of diseases, including cancer and cardiovascular disease. Supplements containing conjugated linoleic acid (CLA) have powerful antiobesity and hypolipidemic properties. Linoleic acid therapy was observed to increase body protein levels while at the same time lowering body fat levels. CLA supplementation increases adipocyte lipolysis while decreasing fat accumulation. Probiotics are a type of fermented food that promotes good health. Lactobacillus acidophilus have a hypocholesterolemic impact by suppressing the activity of 3-hydroxy-3-methylglutaryl CoA reductase, it is a crucial enzyme in the production cholesterol (Figures 2 and 3) [52].

Figure 2.

Functional foods and its bioactive component.

Figure 3.

Bio-active compound and their role in life style related disease.

7.1 Nutraceuticals

The human lifestyle has improved dramatically over the last few decades, but it has made some new pals in the shape of “lifestyle linked metabolic disorders.” The main suspect in the nutritional disaster that led to the current condition of health is erroneous eating habits. Stephen DeFelice invented the word nutraceutical in 1989, defining it as “a food and any component of food beneficial for the treatment and management of human health [53]. Many phytochemicals like antioxidant, glycosinolates, carotenoids, flavonoids, phytoestrogens and dietary fiber are the most common use nutraceuticals. Bioactive compounds are presents in plants naturally show good response to human health like flavanols are present in green tea, resveratrol in grape seeds, lycopene in tomatoes and anthocyanins in blueberries etc. Flavonoids have an inverse connection between dietary intake and the risk of diabetes and cardiovascular disease. In human umbilical vein endothelial cells (HUVEC) stimulated by angiotensin II, the epigallocatechin-3-O-gallate (EGCG) flavanol present in green tea inhibited the protein and mRNA expression of VCAM-1 and ICAM1 genes in a concentration-dependent manner (10 to 50 _M). Later research discovered a link between flavan-3-ol consumption and a lower risk of coronary heart disease mortality. Phloridzin, a dihydrochalcone, has also been shown to play a function in the treatment of postprandial hyperglycemia [54]. The use of dihydrochalcone and quercetin at various doses lower the level of blood sugar in type 2 diabetes mice and also quercetin supplementation lower the cholesterol level. In liver tissue dietary quercetin supplementation increase the activity of many antioxidant enzymes like glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT). Quercetin supplementation lower the expression of PPAR it is used for hyperglycemia, hyperinsulinemia, and dyslipidemia. The use of naringenin-7-O-glucoside in a dose dependent manner improved the cardiac H9C2 cell line. Polyphenols found in lemon, such as flavanone, were found to protect against obesity caused by a high-fat diet. Lemon is the rich source of polyphenols like naringin, eriocitrin, and hesperidin, has higher levels of PPARs and acyl-CoA oxidase expression, as well as a lower body weight. The supplemented diet decreased insulin resistance in experimental animal models by altering blood insulin and glucose levels, according to the findings. Polyphenol present in citrus has vasculoprotective properties, which is very beneficial for cardiac patients. As a result, nutraceuticals have the ability to control and/or prevent nutrition-related disorders in addition to providing nutrients [55].

7.2 Future perspective

Nutrigenomics is the application of high-throughput genomics technology to nutrition studies. If it is used correctly, it will promote a better understanding the effect of diet on homeostatic control and metabolic pathway, the regulation is disrupted in initial stages of a diseases related to diet. In the future, nutrigenomics will enable efficient dietary intervention to restore normal homeostasis as well as prohibit diet-related diseases.

New commercial representations for individualized nutritional advising established on a person’s DNA were also highlighted as a result of the knowledge integrating technology into health sciences. In this approach, organizations concerning the health-care system must act to control these commercial representations in order to protect patient’s honesty while also improving the organization’s nutrition focus performance.

8. Conclusion

Nutrigenomics and nutrigenetics are emerging disciplines that are expanding a variety of fields of study, with medicine, heredities, and diet. Population studies, large sample sizes, with proper experimental designs, scientific trials, and product-specific trials in people selected for specific genetic variations must now be empowered and examined using the massive amount of data obtained by GWAS. The ultimate purpose is to make more effective dietary intervention for individual techniques for preventative medicine and for the better quality of healthy life. Indeed, knowing very relevant to modulations in gene and diet could assist to profile the general dietary recommendations for each population from a Public Health perspective.