26 ISSN 1120-1770 online, DOI 10.15586/ijfs.v35i1.2262 P U B L I C A T I O N S CODON Italian Journal of Food Science, 2023; 35 (1): 26–40 Nutrigenomics: linking food to genome Asma Jabeen1, Geetika Malik1, Javid Iqbal Mir1, Rozy Rasool2* 1Central Institute of Temperate Horticulture, Indian Council of Agricultural Research, Srinagar, Kashmir, India; 2Department of Entomology, Punjab Agricultural University, Ludhiana, Punjab, India *Corresponding Author: Rozy Rasool, Punjab Agricultural University, Ludhiana, Punjab, India. Email: roziarasool24@ gmail.com Received: 25 July 2022; Accepted: 28 November 2022; Published: 26 January 2023 © 2023 Codon Publications OPEN ACCESS REVIEW Abstract Nutrigenomics has an undoubtedly immeasurable potential for revamping human health. It has become an important regimen due to its consequential role in medical and nutritional sciences. It is an interdisciplinary science that amalgamates the information from physiology, pathology, genetics, molecular biology, and nutrition to establish the effects of ingested nutrients on expression and regulation of genes. The ultimate aim of nutrige- nomics is to ascertain the nutritional requirement of an individual in accordance with genetic makeup. Moreover, it aims to purvey treatment in the management of certain ailments having a dietary role based on individual’s genomic profile. Therefore, vast research in the field of nutritional genomics is a dire need to make people aware regarding their health and diet relationship. Here, we have given an overview of nutrigenomics coupled with novel technologies to produce utilitarian information for health professionals and researchers by divulging certain prop- erties that interfere with the genomic machinery. Keywords: gene; interaction; micronutrients; nutrigenomics; nutrition Introduction Although our connection with food is complicated and ever-evolving, our desire for it is fundamental (Grayson, 2010). Influence of diet and environment on the health of an organism is not a new concept (Emilien and Hollis, 2017). Nature alone cannot contribute to molec- ular mechanism that eventually governs the health of a human being (Mead, 2007). The exogenous environ- mental factors that also include dietary nutrients and the genetic makeup of an individual play an important role in expression of a phenotypic trait via the central dogma of biology (Reddy et al., 2017). Over the 20th cen- tury, nutritional scientists focused on the discovery, use, and administration of vitamins and minerals in order to treat the deficiency diseases such as scurvy in the case of vitamin C deficiency; colon cancer, heart disease, and immune dysfunction due to vitamin E deficiency; colon cancer, heart disease, and immune dysfunction due to folic acid deficiency; kwashiorkor and marasmus due to protein deficiency; nerve problem and memory loss due to deficiency of niacin (Dwivedi et al., 2014; Mitra et al., 2005). Malnutrition has repeatedly been shown to be common among hospitalized patients in modern devel- oped societies. We usually mention that in the developed countries such as the USA, UK, Spain, The Netherlands, and Canada, due to a wave of non-communicable dis- eases, there has been a shift from infectious disease predominance to communicable disease epidemic. So, the center of interest of nutritional science and modern medicine shifted to investigation on optimization and maintenance of homeostasis at all levels, namely, cellu- lar, tissue, organ, and at whole body (Afshin et al., 2019; Mohan et  al.,  2007; Raj et  al.,  2007). This requires the basic understanding of the effect of nutrients at molec- ular level, involving nutrient-related interactions at the genome, proteome, and metabolome levels of individu- als, which led to the shifting of nutrition research from Italian Journal of Food Science, 2023; 35 (1) 27 Nutrigenomics makeup or genomic profile, development of new drugs would become the gold standard (Brand et  al., 2021). A renowned biologist and director Professor Yvonne Dragon, Division of Systems Toxicology, believes that new biological understanding will come from familiarity of genes, proteins, and metabolites to fight common dis- eases (Kumar, 2007a). Role of food in disease prevention and management In recent years, food has become the central dogma for nutritionists in establishing interaction between lifestyle- associated metabolic diseases. Reconsideration of “food as medicine” by general public, scientific developments in health sector, and demand for disease-combating diet has opened new area for intervention in health-related issues, which allows individuals to improve their health and prevent diseases (Ohlhorst et  al., 2013). Dietary fibers have a protective effect against bowel cancer (Kelley et  al., 2007). Growth of colonic tumors in both in- vitro and in-vivo systems is inhibited by consumption of fish oil which is rich in omega-3 fatty acids (Syvertsen et al., 2007). Fruits and vegetables rich in bioactive com- ponents can prevent carcinogenesis by several mech- anisms such as blocking metabolic activation through increasing detoxification. Detoxification enzymes such as flavonoids, phenols, isothiocyanates, allyl sulfur com- pounds, indoles, and selenium can be modulated on con- suming plant foods (Fuller, 1992; Mitall and Garg, 1992). Intake of proper diet with sufficient minerals and vita- mins that are involved in regulatory and enzymatic pro- cesses reduces the risk of cancer. The deficiency of these micronutrients may lead to abnormalities. For example, zinc and folate are involved in DNA repairing process. Further natural compounds from plant source such as apigenin (celery, parsley), curcumin (turmeric), epigal- locatechin-3-gallate (green tea), resveratrol (red grape, peanuts, and berries), genistein (soybean), and allyl sulfur (garlic) have been reported to affect the cell cycle by dif- ferent mechanisms (Farouque et al., 2006). Personalized nutrition Nutrigenomics contribute in the designing of optimized dietary intervention strategies to restore and improve metabolic homeostasis, improve health and wellbeing, and prevent diet-related diseases. However, personal- ized diets that could be uniquely tailored according to the specific demands of a given individual considering his/her genetic background, lifestyle, and history are also included here. The speed of penetration of this new sci- ence in daily life is expected to come from both the diver- sity and complexity of food and food practices and the physiology to molecular biology and genetics, giving rise to a new approach of nutrigenomics (Neeha and Kinth, 2013). Earlier, nutrigenomics was defined as “the effect of nutrients on the expression of an individual’s genetic makeup” (Mead, 2007; Riscuta, 2016). Recently, the defi- nition was broadened to understand the influence of nutrients on the genome, transcriptome, proteome, and metabolome (Ronteltap et  al., 2009). It involves charac- terizing the gene products, their physiological functions, and interactions (Neeha and Kinth, 2013). It also analyzes the effects on gene expression due to the bioactive food components (nutrients and non-nutrients) (Alagawany et al., 2022; Koziołkiewicz, 2011). Bioactive food components act as dietary signals (Chadwick, 2004) and from a nutrigenomics point of view, cellular sensor systems such as peroxisome proliferated- activated receptor γ (PPARγ) and retinoid X receptors (RXRs) recognize these dietary signals which influences the expression of genes, synthesis of proteins, and pro- duction of metabolites (Amin et al., 2012). Nutrigenomics seeks to understand how nutrition influences homeosta- sis due to these dietary signatures (Müller and Kersten, 2003). It also aims to understand the mechanisms that influence the genetic susceptibilities (van Ommen and Stierum, 2002) by identifying the genes that sway the risk of diseases related to diet on a genome-wide scale. Origin of Nutrigenomics With the advancement in science and technology, partic- ularly after the completion of the human genome project, scientists appeared skeptical and started questioning like (1) Are gene expressions and metabolic responses the outcome of interaction between genotype and environ- ment (including nutrient)? (2) Will metabolic processes sway the individual in response to gene expression? (3)  How does nutrient–gene interaction lead to the pre- scription of exact diets (Cozzolino and Cominett, 2013)? To answer the above questions, a new subject in the form of nutrigenomics came into existence (Dauncey, 2012). The term “nutrigenomics” was first described by Peregrin (2001) and subsequently appeared in a review published in the journal Current Opinion in Biotechnology (van Ommen and Stierum, 2002). There are several problems with our health system. Firstly, we actually treat people after they get sick, neither do much to keep them healthy nor understand what’s going on while they are healthy; and secondly, the one size fits all approach, that is, giv- ing people the same treatment even though they are all individuals and may respond differently. Human genet- ics so far has largely focused on explicit genetic diseases with possible genetic basis. There have been extremely limited therapeutic benefits, apart from some diag- nostic applications. Based on an individual’s genetic 28 Italian Journal of Food Science, 2023; 35 (1) Jabeen A et al. Nutrients behave as transcription factors after inter- acting with a receptor, which binds tightly to DNA and intensely induces gene expression. For instance, as in the case of lac operon, which is by default turned off if lactose is not present in a cell (e.g., bacterial cell) (Siddique et  al., 2009). The lacI inhibitor gene binds with promoter region and as a result will not allow RNA polymerase to transcribe, and hence no tran- scription of DNA takes place. However, if lactose is present in the medium, it will interact and change the structural conformation of lacI, thus losing its capac- ity to attach with the promoter. RNA polymerase easily binds with the promoter to transcribe the structural genes (lacY, lacA, lacZ) to produce proteins such as β-galactosidase, permease, and transacety- lase, respectively. These proteins help in the uptake and breakdown of lactose to release energy. 2. DNA susceptibility to transcriptional machinery and regulation of chromatin structure Nutrients can alter the structure of DNA by a process known as epigenetics (Park et  al., 2017). Epigenetics denotes continual DNA configurational changes without change in sequence that results in the alter- ation of expression of genetic material (Table 1). The sustained effects of epigenetic mechanism are mediated by chromatin remodelling and methyla- tion of DNA (Liu and Qian, 2011). A methyl group is added to cytosine base to repress gene activity, or tails of histones are attached with combination of different molecules that alters activity of the DNA wrapped around them and ultimately gene expres- sion (DNA methylation) (Fuks, 2005). Similarly active chromatin, that is, non-methylated cytosine and acetylated histones indicate that gene is active and hence transcription is possible. On the other hand, silent chromatin, that is, methylated cytosine and non-acetylated histones indicate that gene is silent and hence transcription is inhibited. The folic acid– rich diet influences DNA methylation during folic acid metabolism and can switch off some import- ant genes (Colson et  al., 2017; Crider et  al., 2012). Dolinoy et  al. (2006) in an experiment reported the role of folate-rich diet in mother mouse, wherein methylated IAP sequences of the offspring genome and the silencing of agouti gene resulted in normal brown color of child coat, whereas, folate-deficient diet resulted in yellow coat color, obesity, and tumors. 3. Prevention of DNA damage Cytokinesis-blocked lymphocyte (CBMNcyt) with micronucleus assay is commonly used with periph- eral blood lymphocytes and is presently the best biomarker for nutritional genomic studies of DNA damage. The extent of chromosomal DNA damage is complexity of our metabolic systems. Our diet is omnivo- rous and consists of a variety of plants, animals and their derived products, water, as well as fungi, yeasts, and a diversity of bacteria. In the past, many food compounds were dismissed because no obvious nutritional roles were known for them. Most foods are a vastly complex and synergistic or non-synergistic mix of several nutrients and many other components, the importance of which is being unveiled step by step. We are exposed to these complex mixtures throughout life, and while our bio- chemical processes extract energy, building blocks, and regulators from food to enable us to grow and function properly they are, in addition, dependent on other fac- tors, including physical activity, feeling and emotion, and social and economic factors (Palou, 2007). Nutrigenomics and Related Terms The nutrient requirements of different individuals dif- fer due to considerable heterogeneity in the sequence of the human genome (Ramos-Lopez et  al., 2017). Nutrigenetics explained this genetic difference as the key basis for diverse response to the diet among differ- ent individuals (Elsamanoudy et  al., 2016; Farhud and Yeganeh, 2010). These differences may not be at whole gene level but rather can be at single nucleotide poly- morphisms level (Irimie et  al., 2019). Thus, both nutri- genetics and nutrigenomics are two sides of a same coin (Figure 1). It holds much promise for providing better nutritional advice by identifying the dietetic components having both detrimental and beneficial health effects. It also determines the necessity of individual nutritional requirement based on genetic makeup and understands the association between diet and chronic diseases (Sales et al., 2014). This can occur in three ways: 1. Regulation of transcription factors and transcrip- tion process Figure 1. Mechanisms of influence of nutrients on gene expression. Nutrient Absorption Nutrient Utilization Food/Nutrient Tolerance Nutrient Requirement Food/Nutrient Genetic Variation N u tr ig e n e ti c s N u trig e n o m ic s Genome Evolution/Selection Genome Mutation Rate In-vitro Genome Viability Genome Programming Gene Expression Italian Journal of Food Science, 2023; 35 (1) 29 Nutrigenomics a biomarker for gene amplification (Figures 2 and 3). Similarly, Fenech (2012) also reported that DNA damage can be caused due to deficiency or excess of nutrition and that the effects are of the same magnitude as that of many common environmental toxicants. Diet-gene regulation/Nutrients and gene expression Nutrigenomics illustrates the influence of nutrients on gene or protein expression that is regulated at specific time under particular environment and also generates response that results from simultaneous functioning of gene or protein networks in regulation of related human disease or disorder. In recent time, there is more inter- est in nutrigenomics research to understand the effects of nutritious food and medication on metabolic disorders measured by the occurrence of micronuclei in lym- phocytes. The accumulation of micronuclei in the CBMNcyt assay is particularly sensitive to nutri- tional deficiency or excess. Mead (2007) reported the association of micronuclei with nutrition and noted in studies that even moderate folate deficiency within the physiological range in cultured lympho- cytes caused as much DNA damage as 10 times the annual allowed limit of exposure to X-rays. Basically, micronuclei originate from chromosomes that fail to engage the spindle during nuclear division or from acentric chromosome fragments and act as biomark- ers of chromosome loss or chromosome breakage, respectively. By using a cytokinesis-blocking agent (cytochalasin-B), once-divided cells that can express this damage are identified as binucleated cells. Within these binucleated cells, it is also possible to measure nucleoplasmic bridges, which arise from dicentric chromosomes and nuclear buds (NBUDs), Table 1. Key plants elements with epigenetic modifications. Sl. No. Key plants Bioactive element Epigenetic functions Reference(s) 1. Apples Phloretin Demethylation, reexpression TSGs, HDAC inhibition Orlikova et al., 2012; Paluszczak et al., 2010 2. Broccoli Isothiocyanates Chromatin remodeling, activation of p21 gene, induces DNA methylation and gene reactivation (cyclin D2) Ho et al., 2009; Hsu et al., 2011; Myzak et al., 2004 3. Cashew nuts Anacardic acid HATi, DNA repair Balasubramanyam et al., 2003; Link et al., 2010 4. Fenugreek Rhaponticin DNA repair and gene reactivation Wani and Kumar 2016 5. Citrus Hesperidin DNMT inhibitor Fang et al., 2007 6. Cinnamon Coumaric acid DNMT inhibitor, increases p53 acetylation Olaharski et al., 2005; Stavinoha and Vattem 2015 7. Coffee Caffeic acid DNMT inhibitor Lee and Zhu 2006 8. Garlic Allyl mercaptan Histone acetylation, HDAC inhibitor Nian et al., 2008 9. Grapes Resveratrol DNMT inhibitor, induces DNA demethylation and gene reactivation Howitz et al., 2003; Paluszczak et al., 2010; Stefanska et al., 2010 10. Soyabean Genistein DNMT inhibitor, decreases HDAC activities, increases acetylation at TSG Bosviel et al., 2012; Fang et al., 2005; Majid et al., 2008 11. Tea Epigallocatechin gallate (EGCG) DNMT inhibitor Fang et al., 2003; Lee et al., 2005 12. Tomatoes Lycopene Induces DNA demethylation and gene reactivation (GSTP1, RARbeta, HIN-1) King-Batoon et al., 2008 13. Red pepper Capsaicin DNMT inhibitor Srinivasan 2013 14. Turmeric Curcumin DNMT inhibitor Marcu et al., 2006; Shu et al., 2011 15. Ginger Gingerol Reduces platelet aggregation and LDL atherogenic modifications Tchombe et al., 2012 16. Mango, Blackberry Gallic acid HATi Choi et al., 2009b 17. Frequently found in fruits and vegetables Quercetin DNMTi, induces p16 promoter, demethylation and gene expression Howitz et al., 2003; Tan et al., 2009 18. Red cabbage, red onion Cyaniding DNMTi Paluszczak et al., 2010 19. Found in walnuts, many other fruits and vegetables Myricetin DNMTi Fang et al., 2007; Lee et al., 2005; Paluszczak et al., 2010 30 Italian Journal of Food Science, 2023; 35 (1) Jabeen A et al. carbohydrates increase the expression of ChREBP (car- bohydrate response element-binding protein), which regulates lipid and glucose metabolism at the transcrip- tion level, thereby contributing to the development of metabolic diseases (Lizuka, 2017). The ChREBP plays a significant role in glucose intolerance, fatty liver, and dys- lipidemia in humans (Benhamed et al., 2012). Effect of lipids on gene expression Profound effects of fat on gene expression led to alter- ation in growth, differentiation of cells, and metabo- lism. Lipids activate various transcription factors such as PPARs, SREBP-1, LXRs, HNF4, and FXR (Table 2) responsible for lipogenesis, glucose metabolism, and so on. (Georgiadi and Kersten, 2012). However, PPAR (per- oxisome proliferator–activated receptor), an import- ant transcriptional factor that is copiously expressed in enterocytes, mediates the effects of dietary lipids on gene expression (Bordoni et al., 2021). Besides regulating various functions such as intestinal nutrient transport and metabolism, intestinal choles- terol flux, intestinal motility, and lessening oxidative stress, PPAR acts as a master regulator of fatty acid catabolism. So, PPAR is therapeutically important for patients suffering from inflammatory bowel disease (Reen et  al., 2015). The nutritional effect of these fatty acids verily depends on the level of saturation. The ω-3 polyunsaturated fatty acids as anti-inflammatory agents interact with genes involved in cancer and various inflammations, hence proving their role in nutrigenetics (Deckelbaum et  al., 2006). They also have a significant effect on cardiac arrhythmia (Brouwer et  al., 2002). Similarly, oleic and linoleic fatty acids decrease plasma levels of low-density lipoprotein and cholesterol (Sacks and Katan, 2002). Effect of proteins on gene expression Protein kinase C (PKC), calcium ion (Ca2+), and K+ channel proteins influence the normal level of insulin secretion by increasing ATP to ADP ratio through glu- cose metabolism and closes K+ ATP channel, leading to depolarization of β-cells (Szymczak-Pajor and Sliwinska, 2019). Fekete and Brown (2007) reported that protein- rich diets result in the moderation of total body fat by causing a shortage of mRNA which is essential for fatty acid synthase gene expression in the adipocytes. Similarly, a low input of essential amino acids triggers reduction in synthesis and also alters the functions of norepinephrine and cAMP by means of a protein called CHOP (or C/EBP, also known as a stress-responsive tran- scription factor) (Zhang et  al., 2002). It attaches with associated with lifestyle transition. Dietary interventions are supposed to play essential role in maintenance of an individual’s well-being and immunity transformation. Effect of carbohydrates on gene expression The simplest monosaccharide (glucose) in nature pro- vides a best model of how living organisms deal effec- tively by developing regulatory mechanisms with a varying level of nutrients supply (Lee et  al., 2008). Glucose is the primary physiological stimulus in the β-cells of pancreas for the regulation of insulin synthe- sis and secretion (Yamashita et  al., 2001). Furthermore, expression of genes encoding lipogenic and glycolytic enzymes, for example, acetyl-CoA carboxylase in liver is induced by glucose in presence of insulin (Henquin, 2000). Thus, it plays a key role in transcriptional regu- lation, though insulin and glucagon were long known as critical in regulating gene expression. (Sanhueza and Valenzuela, 2012). Unbalanced diets increase the risk of developing chronic diseases by altering nutrient–gene interactions (Fukasawa et  al., 2010). Diets rich in excess Figure 2. Expression of micronuclei and nucleoplasmic bridges during nuclear division. Figure 3. Biomarkers scored in the cytokinesis-block micronucleus cytome assay. Micronucleus formation Nucleoplasmic bridge formation C Y T O C H A L A S IN -B B L O C K C Y T O K IN E S IS B L O C K BNC with NBUD, Gene Ampli cation BNC with MN, Chromosome Breakage or Loss BNC with NPB, Dicentric Chromosome Apoptosis Necrosis G 1 ,S,G 2 G 0Genotoxic Italian Journal of Food Science, 2023; 35 (1) 31 Nutrigenomics 1. Transcriptomics The study of expression of genes at the mRNA level is known as transcriptomics. There are sev- eral methods to contour gene expression, however, DNA micro array is the most popular one. DNA microarray technology has successfully measured the changes in genetic expression by evaluating the interactions between diet and genes. In this tech- nique, mRNA transcripts extracted from tissues are subjected to create complementary labeled strand of DNA (cDNA) through Reverse Transcriptase-In Vitro Transcription (RT-IVT). The labeled cDNA is hybridized with a probe (complimentary strand) speckled on a glass or nylon substrate (array) con- taining a set of genes of known sequences. Confocal fluorescent scanner is used to quantify the color intensity, and by examining the resulting image, raw data on gene expression is extracted. Using specific software, raw data is analyzed to determine up- and downregulation of genes with respect to control (Figure 4). Data obtained from microarray can be used by an investigator to establish which genes are expressed differently, that too at mRNA level and thus may be able to design better treatment strategies (Reecy et al., 2006). In comparison to the microarray technology, RNA sequencing technology (RNA-Seq), a novel transcriptomics method has proven tremen- dous analytical capability for gene expression studies. RNA sequencing technology holds great potential for studying nutrient–gene interactions and provides a comprehensive understanding of RNA expression at gene expression enhancers and gets activated by means of stressful stimuli such as DNA damage, cellular growth arrest, and hypoxia (Ren et al., 2017). Effect of micronutrients on gene expression Micronutrients play a vital role in maintaining genome stability (Table 3) by regulating DNA synthesis, methyl- ation, and repair (Fenech, 2012). Savini et al. (2016) and Surendran et  al. (2018) communicated that identifica- tion of indispensable micronutrient-rich foods for DNA replication and repair or for the prevention of genome- damaging events is vital for maintaining proper health and metabolism in individuals. The amount of micronu- trients that appear to be protective against genome dam- age varies greatly between foods (Fenech, 2005, 2008), as well as between individuals, due to taste preferences (Diószegi et  al., 2019; Garcia-Bailo et  al., 2009) or cul- tural or religious constraints (El-Sohemy et  al., 2007). Therefore, careful choices are need of the hour to formu- late patterns of diet that are optimum for maintenance of genome health. Tools of Nutrigenomics New opportunities in the field of science are now pos- sible with the discovery of various “omics” technologies discussed below, to aid in our understanding of the role and impact of various nutrients (nutrition) on individu- al’s health. Table 2. Transcription-factor pathways mediating nutrient–gene interactions. Nutrients Compounds Transcription factors Reference(s) Carbohydrates Glucose USFs, SREBPs, ChREBP Müller and Kersten 2003; Uyeda et al., 2002 Fats Cholesterol PPARs, SREBPs, LXRs, HNF4, FXR Müller and Kersten 2003; Edwards et al., 2000; Horton et al., 2002 Proteins Amino acids C/EBPs Geiger et al., 2016 Micronutrients: Vitamin A RAR, RXR Müller and Kersten, 2003; Rahman et al., 2020; Anitha et al., 2021Vitamins Vitamin D VDR Vitamin K PXR Calcium Calcineurin/NF-ATs Schuster 2006; Rahman et al., 2020 Minerals Iron IRP1, IRP2 Zinc MTF1 Other food compounds Flavonoids ER, NFκB, AP1 ER, NFκB, AP1 ER, NFκB, AP1 Schuster 2006; Baldwin 2019 Xenobiotics CAR, PXR AP1, activating protein1; CAR, constitutively active receptor; C/EBP-CAAT, enhancer binding protein; ChREBP, carbohydrate-responsive element- binding protein; ER, estrogen receptor; FXR, farnesoid X receptor; HNF, hepatocyte nuclear factor; IRP, iron regulatory protein; LXR, liver X receptor; MTF1, metal-responsive transcription factor 1; NFκB, nuclear factor κB; NFAT, nuclear factor of activated T cells; PPAR, peroxisome proliferated- activated receptor; PXR, pregnane X receptor; RAR, retinoic acid receptor; RXR, retinoid X receptor; SREBP, sterol-responsive element-binding protein; USF, upstream stimulatory factor; VDR, vitamin D receptor. 32 Italian Journal of Food Science, 2023; 35 (1) Jabeen A et al. of bioinformatics data. This huge data gathering has a significant advantage in terms of speeding up our knowledge acquisition, which aids nutritionists in harnessing the molecular mechanisms of nutrition to improve production efficiency (Wang et al., 2017) 2. Proteomics Proteome refers to the total set of proteins expressed in a given cell. Proteomics studies are related to expression levels, structure of proteins, and biochem- ical activity. Thus, it addresses the questions of nutri- tional bioefficacy and identifies as well as quantifies bioactive proteins and peptides. In addition to tech- niques such as western blot, enzyme-linked immu- nosorbent assay (ELISA), immune histochemical staining, and mass spectrometry, it also uses protein- specific biomarkers for rapid disease diagnoses (Klopfleisch et  al., 2010). However, major platforms for proteomic studies of biomedical topics are ELISA and MS-based protein assays. Nowadays, MALDI- TOF or TOF-MS is an emerging technology for reli- able and rapid diagnosis and microbial identification. Microbiologists have reported using MALDI-TOF intracellular level in response to dietary interventions (Hasan et al., 2019). The RNA sequencing technique or workflow can be described in three main steps: tissue examination in the lab, bioinformatics anal- ysis of sequence data, and biological interpretation Table 3. Role of micronutrients in maintaining genomic stability. Sl. No. Micronutrients Role in genomic stability Consequences of deficiency Food uptake for remediation Reference(s) 1. Vitamin C and E Prevention of DNA and lipid oxidation Breaking of DNA strands, oxidative DNA lesions and lipid peroxide adducts on DNA Tomato, brussels sprout, Drumstick leaves, kale, chilli, coriander leaves Krajcovicová- Kudlácková et al., 2006; Sorensen et al., 2001 2. Vitamin D Antioxidant activity by increasing the level of glutathione in normal cells, induction of apoptosis in cancerous cells Breaking of DNA strands, chromosome breaks and oxidative DNA lesions Green vegetables, onion, chow chow Schafer and Cockfield 2019; Pizzino et al., 2017 3. Folate and Vitamins B2, B6 and B12 Methylation of DNA, synthesis of dTMP Uracil misincorporation in DNA and DNA hypomethylation Beet root, potato, pepper, turnip, mushroom, garlic, cauliflower Thomas and Fenech, 2009 4. Vitamin B3 (Niacin) Required as substrate for poly (ADP-ribose) polymerase, which is required for cleavage and rejoining of DNA and telomere Impairment of DNA repair, chromosome breaks, mutagen sensitivity Carrot, turnip, celery, mushroom, beans Halliday et al., 2010 5. Zinc Required as cofactor for Cu/ Zn superoxide dismutase, DNA replication, Zn finger proteins Increased DNA damage and chromosomal breakage. Spinach, broccoli Lewis et al., 2005; Yan et al., 2008 6. Iron Required as component of ribonucleotide reductase and mitochondrial cytochromes Reduced DNA repair, increased tendency for oxidative damage to mitochondrial DNA Amaranthus, spinach, cabbage, carrot, beans Zhang, 2014; Canniatti-Brazaca and Germano, 2011 7. Magnesium Cofactor for various DNA polymerases, required in nucleotide excision repair, essential for microtubule polymerization Reduced fidelity of DNA replication, DNA repair and chromosomal segregation, survival of genomically aberrant cells Green leafy vegetables Hartwig, 2001 8. Calcium Plays an important role in chromosome segregation, apoptosis Reduced DNA replication and repair, survival of aberrant cells Agathi, curry leaves Henneke et al., 2017 Figure 4. Schematic representation of micro array technology. Sample Cell line cDNA labelled Image acquisition DataArray hybridization Tissue/Blood RT-IVT labellingmRNA Italian Journal of Food Science, 2023; 35 (1) 33 Nutrigenomics Genetic and nutritional counseling or delivering nutrigenomics services Major barriers in offering nutrigenomics services to the public include lack of proper education in nutrition, genetics, and practitioners (Hudson et  al., 2007). Most practitioners in the healthcare sector do not have enough expertise in molecular testing and clinical genetics as well as lack sufficient knowledge in nutritional science, which is required to infer nutrigenomics tests (Murray adn Botkin, 1995; Roosan et  al., 2022). It is mostly true for physicians, who are usually hesitant to provide advice in nutrition-related matters to patients due to lack of suf- ficient confidence in their nutrition knowledge (Kolasa, 2005). Therefore, practitioners must know how to under- stand and communicate sensitive information during counseling to patients on nutrigenomics (Kurzenhauser and Hertwig, 2006). Besides, sufficient knowledge about nutrition is required to advice patients about modifica- tion in their diets as well as how to quantify risk, to design test outcomes, and to deal with false negative or positive test results (Marteau, 1999), as these are highly suscepti- ble to false impression, even by healthcare professionals. Nutrigenomics Products Nutrigenomics encourages different perspective on foods, healthy, quick to consume and digest, and easy to carry (Ashwell, 2004). According to this, the nutrigenom- ics tools contribute to the search for novel, functional, bioactive compounds intended to have effects like drugs, but without being categorized as drugs (Kruger and Mann, 2003). Functional foods These are very important groups of food having some important bioactive ingredients linked with growth, development, and prevention from diseases (Utkina and Karagodin, 2021). See Table 4. In Japan, nearly 350 food items have been accepted as functional, with each having specified health claims such as for high choles- terol, hypertension, diabetes, and hypotension (Htun et al., 2017). The trends in the development of functional foods include certain minerals, vitamins, and antioxi- dants with reduced calorie content, lower fat content or with healthier fat content as well as having low glycemic index (Garcia-Casal, 2007). Phytosterols, phytoestrogens, fructo- oligosaccarides, omega-3 fatty acids, and polyphe- nols are among others (Nijveldt et al., 2001). Because the inception of agriculture and livestock, genetics has been applied in food for improving the edible plant’s genome. Either due to no load or less pesticides, these are consid- ered as healthier and safer (Alavanja et  al., 2004). Some MS for a variety of purposes, including detection of antibiotic resistance, biological warfare agents, and blood and urinary tract pathogens, and in epidemio- logical studies (Weng et al., 2021). 3. Metabolomics The study which involves chemical processes in the metabolites is called metabolomics. Various tech- niques including nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrom- etry (GC-MS), and high performance liquid chro- matography (HPLC) analyze the whole metabolism. These techniques also reflect the behavior of different patterns of genes to contribute to the knowledge of how food containing over or under nutrients or sec- ondary metabolites, which can affect the health or ill- ness of an individual (Nielsen and El-Sohemy, 2012). Predominantly the two methods, namely, NMR and mass spectrometry are used for conducting meta- bolic studies to identify, quantify, display, and gen- erate profiles of a number of metabolites with more robustness and sensitivity in a body fluid sample. The profiles are then run through monitors to generate data for interpretation (Kumar, 2007b). Potential Issues Associated with Delivering Nutrigenomics Nutrigenomics offers important health benefits for individuals; however, it raises certain legal, ethical, and social issues mainly with respect to nutritional and life- style advice as well as how public may access nutrigenetic tests, as discussed below. Genetic tests and managing nutrigenomics information Nutrigenomics approach like other genome-based sci- ence requires personal genetic information (Vineis and Christiani, 2004). Due to the personal nature of genetic information, it is important that the autonomy of a per- son regarding the decisions based on the information have to be respected (Horne and Vohl, 2020). This indi- cates that the information provided for testing purposes or research must be given without any fear or manipu- lation (Stevenson, 1999). Consent to genetic testing is usually linked with prospects of privacy, which involve liberty from unnecessary tests, and the ability to with- hold information from third parties, namely, bio banks and electronic repositories, particularly in which samples are stored (Anonymous, 2006). As per professional obli- gations, the genetic information is expected to remain a top secret between patients and healthcare professionals (Joffe and Herholdt, 2020). 34 Italian Journal of Food Science, 2023; 35 (1) Jabeen A et al. Dietary supplements Diet is an important factor in cancer etiology and preven- tion. Ayurvedic medicine prescribes many plant-based medicines for the treatment of cancer. Turmeric has shown to be a potent antioxidant and anti- inflammatory agent, with additional promise as a chemo- preventive agent. Many chronic diseases are polygenic and result from interaction between genes and environmen- tal factors. Dietary intervention based on nutritional requirement, nutritional status, and genotype (i.e., “indi- vidualized nutrition”) can be used for the prevention, control, or treatment of chronic diseases such as CVDs, metabolic syndromes, and cancer (Afman and Müller, 2006). These disorders are partly mediated by chronic exposure to certain food components. For example, the association between the amount of calories (Jenkins et al., 1998), the levels and types of vitamins, fat, and car- bohydrates with atherosclerosis, diabetes, obesity, can- cer, hypertension, and other chronic diseases has been demonstrated (Kumar, 2007a). HCA-SX or Super Citrimax, a novel derivative of HCA (dried fruit rind of Garcinia cambogia, also known as Malabar tamarind), is a unique source of (−)- hydroxycitric acid (HCA). It is safe when taken orally and is bioavailable in the human plasma. Under the experimental condi- tions, Roy et al. (2004) demonstrated that HCA-SX sup- plement has been observed to be conditionally effective organizations (environmental) still accuse that these foods act as poison for one’s health and as well as for the environment. However, so far there is no scientific evi- dence indicating any risks to the health of consumers (Vidal, 2009). Transgenic foods Throughout the world, several transgenic foods have been commercialized (Table 5), mostly in Australia, China, the United States of America, and Canada. The known ones are Bt corn, having endotoxin derived from Bacillus thuringiensis, which kills the larvae of stem borer insects and soybeans resistant to herbicide glypho- sate (Broderick et al., 2006). Nutraceuticals Nutraceuticals comprising “any nontoxic food extract supplement that has scientifically proven health benefits for both disease treatment and prevention” (DeFelice, 1995) provide protection against disorders, for exam- ple, cancer, obesity, high blood pressure, cardiovascular diseases (CVDs), gastrointestinal tract disorder, type II diabetes, inflammation, microbial, viral, and parasitic infections, psychotic diseases, spasmodic disorders, and ulcers. (Abbasi et al., 2015). Table 5. Reported sanative effects of foods in different diseases. Sl. No. Foods Diseases References 1. Garlic, ginger, turmeric cloves Cardiovascular and bone diseases Rastogi et al., 2017 2. White brinjal, fenugreek, pomegranate Type 2 diabetes Khan et al., 2009 3. Saffron, turmeric, basil Obesity Alappat et al., 2010 4. Onion, mint, garlic, fenugreek Neurodegenerative diseases and protection against oxidative damage to red blood cells Hwang et al., 2009; Kaviarasan et al., 2004 5. Cardamom, cinnamon Hypertension Davis and Yokoyama, 2011 6. Black pepper, bay leaf Gastrointestinal diseases Speroni et al., 2011 7. Mustard Bladder cancer Bhattacharya et al., 2010 Table 4. Transgenic crops approved for commercial use. Sl. No. Products Altered trait Company Year Trade name 1. Tomato Thicker skin and altered pectin content Zeneca/Petoseed 1995 - 2. Potato AmA1gene (improved protein content) Monsanto Company 2010 Protato 3. Squash Resistant to viruses Ashgrow seeds 1995 Freedom II 4. Rape seed Altered fatty acid composition Calgene Inc. 1995 Laurical 5. Papaya Resistant to viruses Cornell University 1997 - 6. Corn Bt Cry protein Monsanto Company 1996 Yieldgard 7. Cauliflower Introgression of ‘Or’ gene (β-carotene rich) Cornell University - - 8. Soybean Resistant to weedicide Monsanto Company 1995 Roundup ready Italian Journal of Food Science, 2023; 35 (1) 35 Nutrigenomics Alavanja, M., Hoppin, J. and Kamel, F., 2004. Health effects of chronic pesticide exposure: cancer and neurotoxicity. Annual Review of Public Health. 25: 155–197. https://doi.org/10.1146/ annurev.publhealth.25.101802.123020 Amin, T., Mahapatra, H., Bhat, S.V. and Gulleria, S.P.S., 2012. Application of nutrigenomics in food industry: a review. Indian Journal of Horticulture. 2(3–4): 54–59. Anitha, A., Viswambharan, V., Thanseem, I., Iype, M., Parakkal, R., Surendran, S.P., et  al., 2021. Vitamins and cognition: a nutrige- nomics perspective. Current Nutrition and Food Science. 17(4): 348–336. https://doi.org/10.2174/1573401316999200901180443 Anonymous, 2006. United States Government accountability office nutrigenetic testing: tests purchased from four websites mislead consumers. Washington: US GAO. pp. 1–27. Ashwell, M., 2004. Concepts on functional food. Washington, DC: International Life Science Institute (ILSI), ILSI Press. 48 p. Balasubramanyam, K., Swaminathan, V., Ranganathan, A. and Kundu, T.K., 2003. Small molecule modulators of histone acet- yltransferase p300. Journal of Biological Chemistry. 278(21): 19134–19140. https://doi.org/10.1074/jbc.M301580200 Baldwin, W.S., 2019. Phase 0 of the xenobiotic response: nuclear receptors and other transcription factors as a first step in pro- tection from xenobiotics. Nuclear Receptor Research. 6: 101447. https://doi.org/10.32527/2019/101447 Benhamed, F., Denechaud, P.D., Lemoine, M., Robichon, C., Moldes, M., Bertrand-Michel, J., et al., 2012.The lipogenic tran- scription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans. Journal of Clinical Investigation. 122(6): 2176–2194. https://doi.org/10.1172/ JCI41636 Bhattacharya, A., Li, Y., Wade, K.L., Paonessa, J.D., Fahey, J.W. and Zhang, Y., 2010. Allyl isothiocyanate rich mustard seed powder inhibits bladder cancer growth and muscle invasion. Carcinogenesis. 31(12): 2105–2110. https://doi.org/10.1093/ carcin/bgq202 Bordoni, L., Petracci, I., Zhao, F., Min, W., Pierella, E., Assmann, T.S., et al., 2021. Nutrigenomics of dietary lipids. Antioxidants. 10(7): 994. https://doi.org/10.3390/antiox10070994 Bosviel, R., Dumollard, E., Déchelotte, P., Bignon, Y.J. and Bernard- Gallon, D., 2012. Can soy phytoestrogens decrease DNA methylation in BRCA1 and BRCA2 oncosuppressorgenes in breast cancer? OMICS. 16(5): 235–244. https://doi.org/10.1089/ omi.2011.0105 Brand, A., Evangelatos, N. and Özdemir, V., 2021. Placebogenomics: a new concept and tool for personalized medicine and pub- lic health. OMICS. 25(2): 76–78. https://doi.org/10.1089/omi. 2020.0221 Broderick, N., Raffa, K.F. and Handelsman, J., 2006. Midgut bac- teria required for Bacillus thuringiensis insecticidal activity. Proceedings of the National Academy of Sciences. 103(41): 15196–15199. https://doi.org/10.1073/pnas.0604865103 Brouwer, I.A., Zock, P.L., van Amelsvoort, L.G.P.M., Katan, M.B. and Schouten, E.G., 2002. Association between n-3 fatty acid status in blood and electrocardiographic predictors of arrhyth- mia risk in healthy volunteers. American Journal of Cardiology. 89(5): 629–631. https://doi.org/10.1016/S0002-9149(01)02314-1 in weight management and lowered abdominal fat leptin expression in experimental animals as well as in humans. In 2008, Lau et al. showed that supplementation of HCA and niacin-bound chromium (III) is safe and efficacious for weight loss. Conclusions and Future Perspectives The accurate and specific knowledge of dietary require- ments might be useful to mitigate or prevent chronic diseases and also helps to understand the influence of nutrition on homeostasis, metabolic pathways and develop dietary-interventional strategies. Nutrigenomics laid the foundation for understanding variability in pref- erences, requirements, and responses to diet by humans. It acts as a new tool for nutritional research by target- ing the specific gene through nutritional manipulation to alleviate the problems or to get desired performance associated with health and production. This approach would provide long- and short-term benefits to individ- ual’s health by initiating the diet-specific new diagnostic tests against the unfavorable responses to diet, by iden- tification of specific populations with specific nutrient requirements. In future, scientists will constantly con- tribute to develop new innovations in nutrigenomics research, which will certainly update our basic under- standing of nutrient–gene relationship with the help of molecular technologies, especially next generation sequencing. Therefore, future researches should focus on nutrient–gene relationship for nutritional therapy at per- sonal level. 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