1. Nutrigenomics – An emerging field of
science and technology unrevealing interrelationships between nutrients and human
genome using modern tools such as
Transcriptomics,
Metabolomics,
Epigenomics and Proteomics
By
Raffia Siddique, Hafsa Iftikhar, Rabia Ejaz, Tahira Karim
Interaction of food with human genome- Nutrigenomics

2. NUTRIGENOMICS-AN EMERGING FIELD
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List of contents
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Introduction to Nutrigenomics
Emerging faces of nutrition, nutrigenomics and nutrigenetics
Experimental Approaches and Technologies used in Nutrigenomics
Metabolomics-newest tool for Nutrigenomics
Epigenomics has relation in Nutrigenomics
The importance of single nucleotide polymorphisms
Transcriptomics - Nutrigenomics interrelationship
Transcriptomics and micro-array technology
Proteomics
Proteomic technologies
Biomarkers
Effects of different nutrients on human genome
Elements present in food cause potential damage to human genome
Coffee and cigarettes combat rare liver diseases
Nutrigenomics and Ethical control
Looking forward to things which can resolve the ethical , social, legal
issues
 Conclusion and future perspective
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Nutrigenomics – An emerging field of science and technology
unrevealing inter-relationships between nutrients and human
genome using modern tools such as Transcriptomics, Metabolomics,
Epigenomics and Proteomic
Hafsa Iftikhar, Raffia Siddique, Rabia Ejaz, Tahira Karim and Dr.Alvina-The
supervisor
National University of Sciences and Technology
Raffiasiddique_93@hotmail.com,
tahira.karim93@yahoo.com,
rabiaejaz28@hotmail.com,
hafsaiftikhar3@gmail.com
Abstract
Nutrigenomics is emerging field in 20th century, as the old maxim ―we are what we eat‖.
Nutrition and genetics both are play significant role in the maintenance of human health as well
as the development of lethal diseases. Genetic variations toward dietary response and the
nutrients response in gene expression can also be explored by nutrigenetics and nutrigenomics
According to different research studies nutrients is also having the abilities of altering the genetic
expression at gene regulation level, signal transduction or by altering chromatin structure or
changing protein function. The emerging fields of sciences and technology such as
Transcriptomics, metabolomics, Epigenomics, which are very advanced studies, are being used
to go through the nutrigenomics. Metabolomics applications in crop or food analysis are
continually growing and the use of mass spectrometry (MS) and liquid chromatography (LC),
GC-MS and NMR are being used. Epigenetics also known by the soft inheritance is the ability to
change gene activity without changing gene sequence. Diet can alter the epigenetic state of the
genome leading to dramatic deprogramming or reprogramming of large numbers of genes in
metabolic pathways and physiological systems. Transcriptomics extensively report all data that
happens in RNA pool within a system. Genome-wide monitoring of gene expression allows us
assessment of transcription of thousands of genes along with their expression in normal and
diseased cells before and after their exposure to different bioactive components.
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Key words
Nutrigenomics, SNPs, Transcriptomics, Epigenomics, Metabolomics,
nutrigenetics, NMR, mass spectrometry.
Introduction
As the scientific knowledge of nutrigenomics is increasing day by day, the old maxim ―we are
what we eat‖ has been proved a true statement. Nutrigenomics mainly involves the relationship
between diet and genetics, it also discover the beneficial and the inimical effects of different
components. Nutrigenomics deals with the study of effects of diet on activity of individual‘s
gene and health. Dietary components can affect gene expression and genome structure which
means that effect is directly made on Transcription and DNA structure. So, we should
completely know that how diet can interact with human genome and how it affects phenotype.
Up till now the researchers have concluded that dietary health has more importance for optimal
health and disease anticipation than proteins, fats and carbohydrates which can only meet the
minimum daily requirements for the minerals and vitamins. The crux of nutrigenomics is that
variations in genetic make-up and gene expression define our individual specific nutritional
requirements, including how well we absorb and utilize nutrients, and even the amount of food
that we need to consume for optimal health. The genes that an individual inherits are merely one
factor in the exhibition of health or disease. Also, nutrition and genetics both are equally
important in the maintenance of human health an important part in human health as well as the
development of lethal diseases like cancer, osteoporosis, diabetes and cardiovascular disease. So,
nutrigenomics is actually the mixture of nutritional sciences which also include the other highthroughput ‗OMICS‖ technologies like transcriptomics, proteomics and metabolomics. By this
collective knowledge the effects of nutrition on health can be investigated. Variable behavior has
been observed between individuals in response to dietary intervention which is the main topic
under research and practice (Trichopoulou et al., 2008). There are many factors that can
influence the response to diet such as age, sex, physical activity, smoking and genetics(Ordovas,
2007).
Many other factors, particularly diet, play a significant role in gene health. There is no question
that we affect the expression of our genes through our dietary choices. Therefore, the logical
conclusion is that our diets can be personalized to influence our genes. Personalized nutrition
could be proving as a dietary advice to individual‘s genetic outline so can be used in both
prevention and curing of chronic disease. Many whole foods and herbs contain a wide variety of
active phyto-nutrients including carotenoids, coumarins, flavonoids, lignans, plant sterols,
polyphenols, phthalides, sulfides, saponins, and terpenoids all of which have been recently
researched and found to retain important actions in health promotion and disease prevention. The
recent spreading out of interest in this area of research indicates that many diseases can be
lessened by 50% or more—or better yet, prevented—through simple dietary modifications and
appropriate supplementation. (Bouchard and Ordovas, 2012).
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Genotype
Diet
Health and
disease
Phenotype
Figure 1 – Diet‘s relation with health and disease
Emerging faces of nutrition, nutrigenomics and nutrigenetics.
Due to transition in a population shift our health care systems are doing reflecting changes due to
transition in a population shift we need to reduce the costs and chronic diseases by concentrating
on prevention. For this reason, new scientific studies in these specific areas that generate
keenness which seems to be solution of constantly growing issues in our society. Genetic
variations toward dietary response and the nutrients response in gene expression can also be
explored by nutrigenetics and nutrigenomics. In the prevention, management of chronic diseases,
in addition to obesity, diabetes and cardio-vascular another factor has been introduced as new
community-based model of care where affected individuals and his care givers play an effective
role. (Carmen et al., 2012).
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Molecular Nutrition
Proteins
Fats
Carbohydrates
Figure 2 – showing the molecular mechanism of effect on human
genome
Nutrigenetics and nutrigenomics have different impacts on health outcomes by two ways either
by affecting genes expression in different metabolic pathways or distressing the frequency
genetic mutation in the bases of DNA or in the chromosomes which result in the alteration of
gene expression. Inherited genetic variations also specifies the health effects of nutriomes
(nutrients or combination of nutrients) as inherited genetic variation can modify the uptake and
metabolism of nutrients and hence can also involve in the activity of biochemical reactions by
the interaction of nutrient co factor with molecular enzymes.
If the nutritional requirements are customized according to the genetic characteristics of each
individual better health outcomes can be achieved. In addition the acquired genetic individuality
also depends on age, diet and health status (Frazer et al., 2009). Both the nutrigenomics and
nutrigenetics are having common goal of improving health by the interaction of diet and genes.
The optimization of diet provides us a powerful to unstitch the compound relationship between
nutritional molecules, genetic polymorphisms, and the biological system as a whole.
Nutrigenomics explains how food chemicals affecting gene expression, while nutrigenetics
discusses SNPs-single nucleotide polymorphisms which define an individual‘s response to food
according his/her own specific states of health and disease. In the near future people will prefer
to a DNA analysis to have a guideline for avoiding disease and optimizing health issues. How an
individual reacts to a specific ingredient and how it can effects the genes variations can be
explained well by nutrigenetics. It recognizes an individual‘s hereditary predisposition to
disease based on his or her genetic makeup. (Sanchez et al., 2008)
Nutrigenomics and nutrigenetics are two different but closely related terms but not compatible.
Nutrigenetics also involves how the effects of acquired mutations such as cancer can be
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modified in genes related to nutrition specially in uptake of micro nutrients as well as in
metabolism.(Corbin and Zeisel, 2012)
Experimental Approaches and Technologies Used in Nutrigenomics
Genetic information differs at multiple sites of regulation which may be affected by diet. New
developments in genomics, transcriptomics, metabolomics and proteomics have given a more
completed thoughtful that how the effect is being produced by the bioactive compounds over
human health. Healthy bioactive substances can be used for the promotion of health and is being
tested in laboratory by using altered knowhow like cell culture and also research on animal or
human studies regarding bioactive compounds. Each experimental technique gives different
result with unique strength and also having some exact limitations. In these untried studies the
specific role of nutrients and bioactive compounds role should be cleared as it is in vitro, animal,
clinical and epidemiologic studies. In human research studies a variety of ‗OMIC‘ technologies
should be measured as the nutritional lifestyle, clinical physiological, environmental and
demographic factors are involved. How micro flora interacts with host genome, is the topic
under research these days(Ordovas and Corella, 2004a)
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Large complex data sets can be generated and managed by using bioinformatics. High
throughput datasets can be managed stored and analyzed by using bioinformatics knowledge (de
Graaf et al., 2009). Physiological processes can also affect the biological effects of nutrients
and food bioactive. The physiological processes include ―absorption, transportation,
biotransformation, up taking mechanism, storing mechanism and excretion, and cellular
mechanisms of action‖. For example transcription factors regulations. These processes involve
different genes which can change their functional and physiological response to different
nutritional compounds. Diet and gene interactions explains genes affecting different homeostatic
pathways
Figure 3- Using the “omics” of nutrition to identify the dietary factor contribute
to form a phenotype
(Garcia-Bailo et al., 2009) Novel food products has been produced on the genetic basis
considering food been liked or disliked which escort to the development of new food products
according to the ethical rules of society, which may reduce the risk of chronic diseases(Corbin
and Zeisel, 2012) According to different research studies nutrients is also having the abilities of
altering the genetic expression at gene regulation level, signal transduction or by altering
chromatin structure or changing protein function. Diet can cause epigenetic changes for example
methylation of DNA or it may affect the genes expression at genes level. Molecular signatures
also express the genes profile considering specific nutrients. (van Ommen et al., 2010). For
biomarkers identification and the measure of response of individuals to different dietary products
can be measured by using knowledge of proteomics and metabolomics, which could be used to
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block the exposure of diseases and can be incorporated into existing bio banks for nutritional
exposures.
But this is not as simple, a number of challenges need to be resolved relating to handling and
processing After experimentation data should be analyzed by epidemiologically which can
examine the dietary effects and its exposure considering genetic variations in humans. But it is
Also having some limitations like inaccuracies related with estimate nutrient uptake (Scalbert et
al., 2009). However the biological dose will be different in different individuals because of
genetic variability but in case if precise intake levels are known. Its dose is different because the
genetic variability may affect different mechanism differently like metabolism distribution or
elimination of nutrient.(Scalbert et al., 2009). The epidemiological studies also identify some
limitation and flaws regarding genetic polymorphism incorporation into nutrition. For examples
recall bias among case-control studies. One more example is the study on coffee and heart
diseases which clarifies the concept of nutrigenomics and some special dietary factors (Cornelis
et al., 2006). Several studies had examined this connotation and decided that coffee whichever
increases risk, has no effect or decreases danger (Ordovas and Corella, 2004b). As coffee is
complex beverage composed of bioactive compounds. It also contains caffeine which may be
harmful to cardiovascular system. Caffeinated coffee also increases the risk of heart attack
among those individuals who are slow caffeine metabolizers but have no risk of harm in those
who are fast caffeine metabolizers (Cornelis et al., 2006)
Coffee and cigarettes, combat some of the liver diseases (rare liver disease)
Norwegian researchers have conducted out the research which showed that coffee drinkers and
cigarette smokers either male or female have a less chance of getting some of the liver diseases
such as primary sclerosing cholangitis (PSC). PSC is a rare liver condition and it affects the 30 –
40 years aged persons and it is related to cancer of bile ducts. The researchers from the
Norwegian PSC research Center at the Oslo university hospital and the University of Oslo
observed 20% of the daily drinkers and smokers and compared it with 43% healthy controls. It
was concluded that the PSC patients drank less coffee in the present as well as past than those of
healthy controls. So it was shown that coffee drinking helps protect against liver cirrhosis and
liver cancer. The science behind it is that cigarette and coffee drinking produces components
such as nicotine and caffeine, both of which are sympathomimetic and may increase levels of
intracellular cyclic adeno-monophosphate. This adeno-monophosphate is key component which
then prevents from liver cancer or liver cirrhosis(Andersen et al., 2013)
Metabolomics-newest tool for Nutrigenomics
Metabolomics represents the newest ‗omics‘ technology being applied within nutrigenomics. It
exploits several technologies like analytical chemistry such as mass spectroscopy (MS) and
nuclear magnetic resonance (NMR) to capture complete data on the low molecular weight
metabolites, nutrients and other compounds in various human bio fluids, referred to as the
metabolome. Metabolomics applications in crop or food analysis are continually growing and the
use of mass spectrometry (MS) and liquid chromatography (LC), GC-MS and NMR are being
used to acquire more comprehensive view into variation in composition of food in both
nutritional contexts and quality of food. Nutritional quality of crop plant is a direct function of
metabolite content (Memelink, 2004). Metabolomics technology is used to understand well what
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especially happens during crop domestication in order to plan new ideas for more targeted crop
improvements, conduct more adaptations to current requirements. Now we have to identify
molecular markers that can be used to conduct future development of food products (Abulencia
et al., 2006).(Lenhard et al., 2005) used GC-MS based profiling of wild, and a number of
cultivated, tomato species to gain a better insight into what has happened and what has been lost
during domestication. The major analytical methodologies of metabolomics are nuclear magnetic
resonance (NMR) gas chromatography along with the liquid chromatography-mass spectrometry
(LC-MS), and desorption ionization-electrospray ionization-mass spectrometry. Bioinformatics
is applied for the examination and analysis of the data that is derived by the comparison of
different cell conditions. However, metabolomics is not a standardized procedure. It is not yet
possible to compute the whole metabolome or proteome, it is not identified that exogenous food
derived metabolites or how many endogenous metabolites can be quantify in samples of human
or to which amount changes in diet draw changes in metabolic profiles. Quantitative lipid
metabolome data revealed differential effects of dietary fats on cardiac and liver phospholipid
metabolism (Watkins et al., 2001a) and (Watkins et al., 2001b) . This approach mapped changes
in the concentration of lipid metabolites to their biochemical pathways (Watkins et al., 2001b).
This approach was also employed to evaluate the effects of the insulin-sensitizing drug
rosiglitazone on liver, plasma, heart and adipose lipid metabolism in mice and is currently being
used to build a large database of lipid metabolite concentrations in humans. Because many of the
effects of dietary macromolecules on tissue metabolism are reflected in the plasma lipid
metabolomics, metabolome has excellent potential for estimate restrained differences in the
metabolic
response
to
diet
among
individuals.
Using a metabolomics approach to identify key loci will play a significant role in helping to
deconstruct complex metabolic interactions and provide the knowledge ‗to design better crops to
feed the world‘ (Baxter et al., 2006). For example, knowing the genetic basis of the accumulation
of important nutritional vitamins will enable genetic markers to be identified, which can be
incorporated into a standard marker-assisted breeding programme to enable targeted breeding
for the desired level of these highly important micronutrients in our food alongside existing
marker-assisted approaches for more traditional traits such as yield and disease resistance.
Rice is one of the most important food crops in the world; it is the staple of almost half of the
world‘s population and it provides around three-quarters of the calorific intake of people in Asia
To date, few applications for metabolomics on rice have been reported (Tarpley and Vietor,
2007) most of which are not actually directed to grain issues. Metabolomics has, however, great
potential to help advance our knowledge of some of the key nutrition-related targets and
processes currently driving rice breeding and rice research in genera. Rice is a model crop for
genetic analyses because it has the smallest genome of the grasses and synteny provides a
common denominator for using rice to analyses other cereal crops (Balkau et al., 2002). The rice
genome has been sequenced and is being mapped and annotated. The allelic variability is being
catalogued using a diverse set of rice varieties, enabling whole-genome variability to be
associated with different phenotypes (McNally, 2006). Of all the food crop genomes, that of rice
is the most decoded. This will strongly facilitate a synergistic linkage between genetics and
metabolomics for specific improvement of the quality and nutritional value of rice, in highyielding backgrounds, for different environments. Rice breeders strive to develop varieties for
every environment with high yield potential, stress tolerance and excellent grain quality.
However, it is very rare to capture both superior grain quality and superior agronomic
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characteristics in one variety, especially for those bred for unfavorable environments. The
financial benefits of agronomic improvement are lost without high quality.
From this short overview it is apparent that metabolomics has quickly gained its place in modern
plant science in both a fundamental and applied context; nowhere more so than in the field of
nutrition and food quality. Metabolomics is already being applied in fundamental approaches
aimed at gaining a better understanding of the interactive nature and control of important
biochemical pathways in plants. On the more applied side, metabolomics is providing novel
information regarding the composition and potential nutritional imbalance of plant-based
foodstuffs and is helping indicate how more tailor-made strategies could be designed to tackle
key issues of global food quality in the highly contrasting situations typifying developing and
developed countries.
Epigenomics has relation in Nutrigenomics
Our diet interacts with our genes. Nutrigenomics is diet-induced changes in gene expression
that can influence network interactions and cellular information flow and nutritional epigenomics
is Diet-informed epigenetic modifications of chromatin (DNA methylation and histone
acetylation) that can alter gene function and long term health outcomes(National WIC
Conference September 23, 2010) Epigenetics also known by the soft inheritance is the ability to
change gene activity without changing gene sequence , it means that there are no mutations
involved. Typical epigenetic affects include DNA methylation which means gene silencing and
Histone acetylation describing gene activation. Diet can alter the epigenetic state of the genome
leading to dramatic deprogramming or reprogramming of large numbers of genes in metabolic
pathways and physiological systems. Foods contain many inhibitors and stimulators of chromatin
remodeling enzymes (DNA methylases and histone acetylates and deacetylases), making
nutritional intervention a possible way to ―reprogram‖ the epigenome to promote health and
prevent disease. Nutritional genomics represents a new approach for translating the exciting
discoveries of genomic research into appropriate actions for using nutrition to prevent disease
and promote health for individuals, families, and communities. Observational studies have
generated the hypothesis that during critical periods of growth, the fetus and the newborn may be
programmed (fetal and postnatal programming) in a permanent manner by conditions such as
nutritional insults, and environmental effects in utero and during early life. New knowledge now
shows that epigenetic modifications may account for the increasingly predictable links between
the prenatal and early postnatal nutritional environment and adult health and disease. Limited
nutrient availability in early and later life appears to precipitate the appearance of adult-onset
diseases (and also childhood) obesity, cardiovascular disease, type 2 diabetes, and cancer.
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.
Figure-4
Dietary signals /profiles
These are patters of gene expression, protein expression and metabolite production in response to
particular nutrient or nutritional regimes can be viewed as dietary signature.
Use of Dietry signals in Nutrigenomics research
Nutrigenomics seeks to examine these dietry signatures in specific cells,
tissues and organisms and to understand how nutrition influences
homeostasis. Dietry signatures can be used to identify (early ) molecular
biomarkers.
The importance of single nucleotide polymorphisms
In simple classification of nutritionally modifiable genes as constitutive or inducible, it is the
second order classification of these genes as being polymorphic or wild type that motivates
highly variable response of humans to a given diet. Most commonly used form of polymorphism
is single nucleotide polymorphism (SNP).In consideration of facts that approximately one SNP
per 1.08 kilo base of gene sequence or 1 SNP per 1.91 kilo bases of DNA sequence(Chakravarti,
2001). Herein some criteria may offer some regulation. As SNP is of practical importance in
nutrigenetic standards, the SNP is probably be present with several numbers of properties such
as reveal high frequency in general population of interest, regulating proteins at rate limiting
steps or at biological cascades in intermediary metabolism, and having helping biomarkers that
offer substitute measures of clinical effect. Now days, only few SNPs can fulfill our criteria, but
we can learn a great contract from those that follow the whole criteria. The biology of interleukin
1 (IL-1) and methylene tetra hydro folate reductase (MTHFR) are instructive examples of the
significance of coding and non-coding SNPs respectively, as genetic levers for organization
health. (Chakravarti, 2001).
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Transcriptomics - Nutrigenomics interrelationship
Transcriptomics is defined as the main sub leading of molecular biology that deals with the study
of messenger RNA molecules being produced in discrete individual or population of a particular
cell type, which means that the study of transcriptosome, where transcriptosome is reffered as
complex of all RNA molecules in residents of cells (Chakravarti, 2001). This field can be
applied to all sets of records in known organisms. The transcriptosome reproduce those types of
genes that are being dynamically articulated at any time. The study of transcriptosomics also
reffered to as expression profiling, often using productive techniques based on DNA micro-array
technology and RNA sequencing. Transcriptomics extensively report all data that happens in
RNA pool (that is transcriptome or all expressed genes)
within a system (for example body fluid, a cell or
tissue).Cellular functions are arbitrate by gene expression
relating messenger RNA (mRNA) (Cordero et al., 2008b).
Transcriptomics does not provide direct summary of
information from the genome, nor is it produced only
during DNA-dependent RNA synthesis
(Jones and
Ashrafi, 2009) . We can modify the sequence of RNA
molecule by using different processes such as RNA
editing and differential splicing method. Many vital
nutrients and bioactive food components can provide as
important regulators of gene-expression patterns by
modifying gene translation and transcription, thereby
changing biological responses such as cell growth,
differentiation and metabolism. These all methods play
important role in disease process (Jones and Ashrafi,
2009). DNA microarray techniques allow immediate
estimation of thousands of genes of transcription and theirFigure-5 Nutrigenomics and
comparative expression between
diseased cells and normal cells both before and after contact to different dietary components
nutrigenetics inter-relationships
(Jones and Ashrafi, 2009).
Transcriptomics and Microarray Technologoies
―The impact of a number of dietary factors on human phenotype is not completely figured out by
DNA modification. The phenotype of a person can be regulated by the regulation of the pace of
transcription of genes which is by food components and this aspect is really intriguing aspect of
Transcriptomics. The regulation of gene expression pattern is controlled by not only bioactive
food components but host of some essential nutrient elements as well. The processes which
mediate important role in disease onset in human body such as metabolism, cell growth and
differentiation are all modified by the process of transcription and translation which in turn are
modified by vitamins, minerals, various phytochemicals, and macronutrients. The interaction of
bioactive food components with various cellular processes and their action is widely studied by
the development of latest microarray technologies and these technologies are being used by
nutritional scientists. Genome-wide monitoring of gene expression allows us assessment of
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transcription of thousands of genes along with their expression in normal and diseased cells
before and after their exposure to different bioactive components. Changes which occur in
diseased cells compared with normal cells are provided by latest microarray technology tools.
This statistics should assist in the detection of promising biomarkers for diagnosis of disease,
prognosis prediction and in the discovery of new therapeutic tools. The discovery of appropriate
clinical strategies and introduction of modified medicine, including nutritional preemption
related strategies had been made possible by the use of molecular approach in health and disease.
The expression of a particular gene can be stopped by the use of a phenomenon called RNA
interference. The action of bioactive food and disease condition and characteristics are
demonstrated by the use of RNA interference technology (Cordero et al., 2008a) . An experiment
has been performed by investigators on worm model by using the phenomenon of RNA
interference Caenorhabditis elegans was used as model and its gene expression was disrupted by
the use of this technology to determine the genes which control its fat storage and which is
responsible for increased fat in body. This is tolerable for the identification of fat regulatory
genes core set and specific fat regulators specific pathway (Cordero et al., 2008a). the site of
action of isothiocyanate compounds such as sulforaphane, that arise from broccoli and other food
components was determined by using this technology (Jones and Ashrafi, 2009). As
transcriptomics information becomes available, the targets for treating obesity and other
unhealthful conditions with foods or their bioactive components were also determined.
Proteomics
Proteomics is a central platform in nutrigenomics that describes how our genome expresses itself
as a response to diet (Enzinger et al., 2005). Nutrigenetics deals with our genetic predisposition
and susceptibility toward diet and helps stratify subject cohorts and discern responders from nonresponders Epigenetics represent DNA sequence-unrelated biochemical modifications of DNA
itself and DNA-binding proteins and appears to provide a format for life-long or even trans
generation imprinting of metabolism (Hine et al., 2003). Proteomics in nutrition can identify and
quantify bioactive proteins and peptides and addresses questions of nutritional bio efficacy (Hine
et al., 2003)The interplay between nutrition and health has been known for centuries: the Greek
doctor Hippocrates (fourth century B.C.) can be seen as the father of ‗‗functional food,‘‘ because
he recommended using food as medicine and vice versa. Another example of such long-term
experience is the record of traditional Chinese medicine: Sun Si- Miao, a famous doctor of the
Tang dynasty (seventh century A.D.), stated that, the doctor should first regulate the patient‘s
diet and lifestyle, when the person is sick. The new era of nutritive exploration translates this
rather experimental knowledge to molecular science which is evidence based, because diet
constituents interact with human body at micro and macro level as well. Latest dietary and
fitness study emphases on health promotion, the onset of disease prevention or delay, and
performance optimization. Dietary components are in the form of complex mixtures, which not
only involve the presence and concentrations of a single compound but also relations of
numerous compounds influence food compound bio availability and bio efficacy. Hence, the
necessity of developing and applying comprehensive analytical methods to reveal bioactive
ingredients and their action becomes evident (Kussmann and Affolter, 2009).Proteomics is a
central platform in elucidating these molecular events in nutrition: it can identify and quantify
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bioactive proteins and peptides and addresses questions of nutritional bio efficacy. In this article,
we focus on these latter aspects, update the reader on technologic developments, and review
major applications: we summarize mass spectrometry (MS)-rooted proteomic techniques for
protein identification and quantification and go through a selection of nutritional intervention and
bio efficacy studies assessed by proteomic means.
Many nutrients can modify RNA translation to proteins and the events which are posttranslation, protein activity is also affected by these events. Proteomics is very challenging
process technically; metabolic changes do not necessarily affected by the presence or absence of
proteins. All the nutritional study comprising profile and features of body and dietary proteins,
assimilation, captivation and uptake of nutrients, their function and their role in progression,
duplicate , and fitness, biomarkers of disease and diet status ,individual requirement of nutrition
elements these all have been discovered by using proteomics latest technologies. The proteome
exploration is found to play a role in solving all the major nutrition-associated problems in
living beings for example fatness, diabetes, heart disease, melanoma, aging process, and intra
uterine fetal obstruction are solved by using proteome analysis(Kussmann and Affolter, 2009).
Proteomic technologies
There are number of technologies used for separation of proteins such as two-dimensional
polyacrylamide gel electrophoresis and number of chromatography methods have been applied
as efficient tools for long times(Knowles and Milner, 2003). The analysis of protein has become
possible using MS technologies which include electrospray ionization (ESI), soft ionization
technique and matrix-associated laser desorption ionization (MALDI). These technologies were
invented in late 1980‘s and these techniques are used to vaporize proteins and peptides (Knowles
and Milner, 2003). ). These techniques make use of charge to mass ratio; flight time and electron
trap as chief discriminating parameters for analysis of ionized and vaporized proteins and
peptides in high vacuum of the MS and other latest technologies such as MALDI and ESI
respectively. MS is being used for more than 20 years in proteomics only because of its very
high speed, sensitivity, specificity, resolution of mass ability and mass precision during protein
documentation processes When MS is merged with LC-GC or with MS, and then its efficiency
can further be enhanced in proteomics. Techniques which involve specific protein consumption
2D-PAGE MS and multi-dimensional protein separation and their analysis after protein
separation are mainly four as they are being used frequently in proteomics. These techniques also
involve their analysis after their chromatographic separation. The type of technology being used
depends on the purpose of study and availability of facility in laboratory. Although all of these
methods involve preparation of sample, separation of protein, analysis of MS, and identification
of protein. Several dietary components are recognized that post-transnationally modify proteins
and thus influence their activity. For example, shifts in phosphorylation occur after exposure to
diallyl disulfide (DADS), a compound found in processed garlic. Western blot analysis revealed
that DADS exposure did not affect ERK protein content per se but increased its phosphorylation
resulting in cell-cycle arrest. Using MALDI-TOF MS, major differences in the metabolic
pathway in mitochondria of young and aging monkeys and between males and females monkeys
were reported by a group of scientists, which helps explain risk of cardiovascular diseases with
an aging-associated gender difference. Proteomics also identified up and down regulated proteins
such as vitamin and glucose controlled protein in adipocytes which are treated by insulin and
mammalian cells transcription factors. There are processes such as glycolysis, gluconeogenesis,
oxidation of fatty acid and metabolism of amino acid involve the enzymes whose level differ
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significantly between obese and lean diabetic mice, however their level can be regulated with
peroxisome proliferator triggered receptor activators in these processes (Bluher et al., 2004) .
Future perspective of proteomics
Proteomics is a powerful tool in the transformation of the field of nutritional research. The
comprehensive information about the identification and characterization of dynamic ranges of
protein, diverse physical and chemical properties, and intricate relations is provided by
amalgamation of various proteomics techniques. Chief nutrition related problems in human and
animals are solved by the use of proteome analysis (Davis and Milner, 2004). The vital proteins
that function to control the metabolic pathway and whose degradation ,production and
alteration also affect certain nutrients or other dietary factors are discovered by the use of
advance proteomic technologies ( e.g. genomics, metabolomics, bioinformatics and
Transcriptomics (Wu et al., 2004a, Rhind, 2004) . The complex interactions responsible for
nutrient utilization are aided by these technologies, it also help in identification of promising
biomarkers for nutritious status and advancement of disease, scheming a modern model for
food prevention and mediation of disease (Wu et al., 2004b, Wu and Meininger, 2002).
Biomarkers
New biomarkers are needed for the relationship between health and nutrition to reflect the
efforts of the body to maintain this homeostasis and changes in homeostasis (van Ommen and
Stierum, 2002). Biomarkers linking health with diet will be different than those linking disease
with nutrition. Ideally, the biomarkers should permit simultaneous monitoring of both the
efficacy and safety aspects of the dietary constituents. Classical biomarkers, e.g., single gene or
protein or metabolite, do not allow assessment of physiological actions of a single nutrient and
number of known and unknown biochemical targets. The scenario becomes more complicated
when assessing the efficacy of a nutritional component, because single dietary components are
not spent as separate objects but as component of a dietary mixture. Thus, for prevention of
disease in the development of functional foods is important to get a holistic impression of early
phases of the disease procedure. (van Ommen and Stierum, 2002)
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Effect of different nutrients on human genome
Nutrigenomics is the study of interactions of nutrients present in the food with the human
genome. The variations which do occur in the human genome, it is because of the complexity of
nature of foods prepared as desired by them. There are many examples which illustrate and
explain the existence of different elements present in the foods interacting with the human
genome and leading to the different variations occurring in the human genome such as CoQ10
which is present in human muscle cells has shown effects on 12,000 genes(Rosenfeldt et al.,
2002). Also the most important vitamin which is vitamin D is responsible for the absorption of
intestinal calcium and phosphate. Research has shown that vitamin D3 affect 20,000 genes in
human prostate cancer cells(Rengaraj et al., 2003)
While Nutrigenomics is dealing with the effect of diet on genome mean while new research at
University of Florida was made which studied the effect of specific diet on human genome and
chronic diseases caused by it. According to the research the effect of zinc was studied on human
genome. They found that zinc has equal ability to turn off and turn on genes in human. some of
the genes were tuned off by less zinc in diet but after experimentation it was found that they
resulted in activation of the variety of white blood cells which protect the body against infections
, but when zinc level increases in body those genes were turned on. In this way scientists treated
various immune related disorders such as diarrhea and malaria by setting value of zinc(Woods,
2003)
―A study conducted in Europe Japan and USA, in which they for the first time showed the
comparison of domestic and wild tomato genes and DNA sequence which were active in them.
This leads to enable breeders to breed new traits into tomato or other crops along with genetic
changes involved in. For example, propagation of new traits into tomatoes often involves
crossing with their wild relatives. The recent study provides with the evidence that there is a
large block of genes from a species of wild tomato is present in domestic tomato, and has
prevalent, unforeseen effects across the whole genome. Maloof and his colleagues studied the
domestic tomato(Solanum lycopersicum) and wild relatives (S. pennellii, S. habrochaites and S.
pimpinellifolium).Comparison of the plant‘s genomes shows the effects of evolutionary traffic
jam, Maloof noted — for example at the original taming in South America, and later when
tomatoes were brought to Europe for agronomy. Among other outcomes, genes associated with
fruit color showed rapid evolution among domesticated, red-fruited tomatoes and green-fruited
wild relatives. In the desert habitats S. pennellii, had quicker development in genes related to
drought tolerance, heat and salinity‖
New technology is giving biologists the extraordinary aptitude to look at all the genes in an
organism, not just a select handful. The researchers studied not just the plants' DNA but also the
messenger RNA being transcribed from different genes. RNA transcription is the process that
transforms information in genes into action. If the DNA sequence is the list of parts for making a
tomato plant, the messenger RNA transcripts are the step-by-step instructions.(Koenig et al.,
2013)
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Elements present in food cause potential damage to human genome
Elements present in Potential damage caused by over dose of these
food
elements
Kidney damage and osteoporosis. Skin burns caused by white
Phosphorous
Zinc
Copper
Aluminum
Nickel
Sodium
Iodine
Potassium
Iron
Lead
phosphorous.
Stomach cramps, nausea and vomiting. anemia, metal fume fever,
skin-irritation
Breathing Cu can cause nose and throat irritation and assimilation
of it can lead to vomiting and diarrhea.
Dementia, memory loss, listlessness, and severe damage
to central nervous system
Lung and nose cancer, larynx cancer along with prostate
cancer
Perspiration of sodium hydro-oxide fumes causes
irritation to skin, eyes, nose and throat. Breathing
sodium causes coughing and sneezing.
Elemental iodine I2 is toxic and its vapours irritates eyes
and lungs
Irritates eyes and nose, throat along with lungs causing
sneezing, coughing and sore throat.
Conjunctivitis and retinitis, inhalation of result in
development of a benign pneumoconiosis, called
siderosis.
anemia, hypertension, Kidney damage, Miscarriages and
subtle abortions
Table 2- Elements present in food cause potential damage to human genome
Nutrigenomics and Ethical control
Human beings are so complex and more complex their habits and desires are. Nutrigenomics is
the science of interaction of gene and nutrients, when this knowledge to human interest they
start to develop the products of their interest or might be they are in need to get that product so
they artificially make the foods having particular nutrient having such modifications which does
act on human genome but everything achieved so quickly and artificially have some drawbacks,
along with the benefits which are got, to be more simple, these are the ethical issues which
affect the lives of the people and the society. Although it is not a bad thing to search but to take
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care of people rights, more importantly their lives, and to keep them happy is the awesome
thing to be achieved.
Customized diets have now been formed such as genetically modified foods (GMO) which
serve to get achieve the purpose but there are some ethical and legal issues related with it. It is
who which decide that whether the GMOs are being liked or disliked, it is the people, some
population of whom loves GMOs and other half of them call it is as Franken foods.
Joint center of bio-ethics (JCB) in university of Toronto in collaboration with the university of
Guelph philosophy, have set to sort out the ethical questions about the Nutrigenomics and all
fields of Nutrigenomics in their joint project of a paper nutrient and genes; science, society and
the supermarket in which they sorted out that if Nutrigenomics is the study of interaction of
nutrients with the food then how the variations in the human genome is brought about the
foods, lead to produces the ethical concerns, so in order to sort out and resolve them.
Research had been started since 2oth century, which is still in the beginning stage, but it had
made scientists to at least propose their actions which they need to perform in order to help
improve the ethical concerns related to customized diets being produced as a result of
advancement in Nutrigenomics. Scientists are interested in the radical changes which are they
going to bring about how food is grown, processed, consumed and hence the formation of
customized diets which alter their genetic makeup.
The thing which is the most considerable is the fact that although Nutrigenomics is beneficial but
there is very less Nutrigenomics experts which do serve the purpose. Primary care physicians are
there but they have minimal training so they are not expert in this field and hence they need
improvement. There is shortage of geneticists and molecular nutritionists. It is required that
Nutrigenomics should be brought in to practice and more work is required in this field (Castle
and Ries, 2007)
The major parts of Nutrigenomics services are classified in to three; one is the utilization of
nutrigenomic knowledge and on the basis of which formulation of genetic test and its
understanding, secondly the calculation of disease vulnerability based on the test results, thirdly
using the nutrigenomic knowledge formulate the dietary commendations. These things are worth
to mention priorly because, these are the components which arise issues ethically, legally and
socially. DTC which means direct to consumer is the most encountering potential ethical issue
faced nowadays because of this emerging knowledge of nutrigenomics which the people don‘t
bother to wait for the results of taking dietary supplements and directly take those supplements
which can prove to very harmful for their health(Holyday et al., 2012)
The current controversy creating ethical social and legal issues arise from the delivery if
nutrigenomic services focusing on the instruction of DTC genetic testing which the nonpracticed people is carrying out. The only solutions to this problem is direct access to testing
services and goes for results first and then go for applying to one own self. So personalization of
diets, followed by the genetic tests can lead to better health of individuals and help reduce the
issues regarding social, legal and ethics.
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Looking forward to things which can resolve the issues
The steps which can be taken to make the future secured and take the possible benefits out of
nutrigenomics and free of the ethical, social and legal issues are genetic tests and more
importantly the assessment of dietary intake with the proper genetic and nutritional counseling to
inform behavioral effects and hence better and healthy outcomes will be produced. If the genetic
tests are considered then, highest standard of laboratory are required. For-example in United
States, the laboratories whether in-house or out sourced, meet the CLIA certification standards,
also other tests might need FDA approvals, especially in those tests where the health outcomes
are involved.
Dietary practitioners have competency in nutritional genomics, have professional skills in doing
to the counseling the patients related to their diet and health. Also it is now evident that the
deficiencies in physicians genetic and nutritional knowledge is very much alarming. It is because
of the financial and other barriers which limit their genetic training in dietetic education so
dietetic professionals face the pressure in this way.
Perspective for future/ Conclusion
Nutrigenomics can benefit from a systems biology approach that use a number of the highthroughput ‗omics‘ technology platforms to identify the nutrient-sensitive gatekeepers of these
disease processes. Each analytic platform (genomics, proteomics, Transcriptomics or
metabolomics) provides essential complimentary information implicit in the unraveling of
mechanisms underlying diet and health.
In order to progress the field, a number of simple, yet fundamental experiments will be required.
For example, within the context of insulin resistance, the metabolic syndrome and T2DM, there
are several organs involved in adipose tissues, skeletal muscle, liver and pancreatic β-cells
How do the gene and protein expression change within and between organs relate to each other.
Which tissue(s) is most affected by nutritional interventions? What are the nutrient sensitive
targets for intervention? How do tissue specific alterations in gene/protein expression relate to
the traditional metabolic markers of insulin, glucose and lipid metabolism? How does
metabolomics profiling reflect differences in metabolism? Is the metabolomics approach
sensitive enough to detect nutrient sensitive aspects of insulin resistance? Can these technologies
provide nutrient sensitive fingerprint that reflects metabolic health? It is probable that a lot of
this fundamental work will not be possible in man. Some initial studies investigating the effects
of nutrients on gene or protein expression and the metabolome will be reliant on cell models and
animal studies. Nevertheless we have to determine whether more accessible tissues (e.g.
mononuclear cells in peripheral blood) can be used as a surrogate marker for the more
inaccessible tissues, such as the liver, pancreas, etc. The biggest challenge for nutrigenomics will
be to bring all of this technological expertise to the level of human nutrition.
Within the context of nutrigenetics, it is clear that good advice for one individual may not be
beneficial for another. Therefore the era of ‗personalized nutrition‘ is predicted; wherein genetic
variation and an individual's different responses to food and nutrient interventions present an
opportunity for diet-related disease prevention. To date the nutrigenetics approach has been over
simplistic, focusing on one SNP, a single dietary component and single disease risk factor. The
challenge will be to identify the functional polymorphisms, define interplay between several
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genes, identify the nutrient-sensitive genes, account for gene–nutrient–environment interactions
and understand how dietary interventions can be tailored to be most effective.
Human health and agriculture make use of application of nutrigenomics. This help in production
of enhanced animal and food sources. The application to individual differences in metabolism is
used to focus how the field could proceed to address this challenge and this is just for the
purpose of discussion. The variation in metabolism in response to nutrition is caused by a
mechanism which is not fully known yet. So the main focus of study involves genetic variation
and epigenetic mechanisms. A complete data set which describes the interaction of nutrition and
gene with each other is needed to be studied in order to move forward and develop an
overarching theory for predicting effects of genes on different metabolic variations and
requirement of nutrition. Any practical application to human without the use of these
mechanisms will be defective.
There are number of genes whose function is still not known. There is possibility that these
genes might have role in regulation of metabolism in human. The impact of gene deletion is
being studied on mice phenotype by researchers across Europe and United States. For this
purpose more than 9000 genes are being analyzed by using mice as model animal. A systematic
approach is needed to discover the function of these genes. The latest techniques of genetics and
epigenetics are being evolved rapidly (Wu and Meininger, 2002). . The cost efficient and capacity
bearing ,new generation of techniques are being introduced for high throughput gene sequencing.
These make possible the practical use of these genetic and epigenetic techniques in large
population marks. The cost for gene sequencing can be lowered by using these practical
approaches of gene sequencing in single batch. When identifying sequence is attached to each
individual‘s DNA then it mix together with many subject‘s DNA sequenced ,after that it is sorted
using barcode so that gene sequence of the person can be assembled, this technique is known as
Barcoding technique. Barcoding technique offers the promise for cost-efficient use of sequencing
in nutrigenomic studies. This technique also make possible methylated gene sequencing(van
Ommen and Stierum, 2002).
Acknowledgements
First of all, thanks to Almighty Allah, who had made us such able to think and work as such a
team and then we are very thankful to Dr.Alvina Gull, because of her patient and very sweet
nature, her support and guide was the major reason we are over this article. We as a team are
very happy with this teacher and always be obliged to her.
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