See also: Related OurFood News

Subsections

Nutritional Genomics

The beginning of nutritional genomics


Nutrigenomics

Nutrigenomics is the characterization and sequencing of an organism's genome and analysis of the relationship between gene activity and cell function Nutritional genomics, or food genomics is the specific application of genomics in research pertaining to agriculture, food processing and food consumption. It studies how food, genes and lifestyle interact.

Nutrigenomics covers the entire food chain. Agriculture use food genomics to increase vitality, disease resistance and drought and salt tolerance resulting in increase of yield, reduced loss during storage and transport, enriched micronutritions and microorganism producing auxiliary substances and food ingredients.

The knowledge of biological active components has been developed during the last ten years being the basis for the development of new functional foods, looking forward to tailored functional foods and personalized foods.

Genomics researche is arousing hope that food will be adaptable to individuals' genetic profiles. Genetic susceptibility to disease ranging from intestinal cancer to food infection. Genomics researche is helping to map these phenomena and give food advice to the personal genetic constitution. Consumer will be choosing food on the basis of their own genetic constitution within ten to twenty-five years. People will have a genetic passport that allows them to use personalized nutrition, personal food with a preventive function.[1]

Nutrigenomics is not seen as a product category in itself, but rather as supporting technology for the development of foods of greater nutritional value, and of functional foods. [2]

Jean Baptiste Lamarck developed at the end of the 18th century a theory which modern biologists rated as nonsense.

Lamarck explained nature as being controlled by three biological laws: Lamarck lived from 1744 to 1829. He was a French botanist and invertebrate zoologist. He wrote that acquired characteristics could be inherited to following generations, even not being genetically encoded. Genetic science experienced then a recession. It was only in 1865 that George Mendel published the "Mendel' s Laws" of autosomal inheritance, followed by Charles Darwin with "The Origin of Species" in 1859. Francis Galton (his cousin) rediscovered Mendel' s laws and is considered to be the father of modern genetics.
James Watson and Francis Crick discovered the DNA in 1940's. The Human Genome Project begun in 1990.


Uses of food genomics

Through informatics driven metabolomic analysis it is possible to identify and predict the impact of diet on the health of individuals with different genotypes.


Metabolomics [3]

Mei Wang and colleagues 2005 define metabolomics as a concept of systems biology, enabling the study of living systems from a holistic perspective based on the profiling of a multitude of biochemical components. The authors stress that it is useful to study natural products, focusing on the synergetic effects of components which had not been considered in the study of single active components. It studies the effect of complex mixtures, such as those used in Traditional Chinese Medicine, in complex biological systems abridging it with molecular pharmacology.


Systems biology explain complex interactions in biological systems [4]

Systems biology is a multi-targeted approach which identifies regulatory hubs in complex networks. Systems biology takes the molecular parts (transcripts, proteins and metabolites) of an organism and attempts to fit them into functional networks or models designed to describe and predict the dynamic activities of that organism in different environments. It focuses on complex interactions in biological systems, claiming that it uses a new perspective (holism instead of reduction).

Systems biology tries to explain properties of a system whose theoretical description is only possible using techniques which fall under the remit of systems biology. These typically involve cell signalling networks, via long-range allostery. Example is given by the authors how the scaffolding proteins NHERF1 and ezrin work in coordination to assemble crucial membrane complexes. [5]

According to Mochida and Shinozaki 2011 Bioinformatics and several new omics layers such as the interactome, epigenome and hormonome have emerged to explain the molecular systems that underlie various plant functions. Novel applications of neutron spin echo spectroscopy explained allosteric signals by nanoscale protein motion. [6]

According to Wagner et al. 2011 systems biology can be pursued at three levels: a) the macro-level, or the dynamics of the biological systems of cells, tissues, and organs, as opposed to conventional, static, single-gene or single-protein snapshots of biological processes; b) the micro-level, or biological interactions at the molecular level; and, most importantly, c) the development of methodologies and research tools. [7]

Metabolome

The small molecule inventory (SMI) or metabolome is a pattern of molecules that reflects the cell's statues. It is the totality of metabolic processes including anabolism and catabolism. It results from the expression of the genome and proteome in response to the cellular environment. The metabolome gives a direct picture of the cells activity and its environment.

The cumulative effects of all expressed and modified proteins represent an information which is stored in the small molecular inventory (SMI) of the cell. These molecules include important cellular function compounds, such as nucleotides, vitamins, antioxidants and catecholamines. This area of researche is called metabolomics.
When taken in its entirety it is not always necessary to know the identity of individual components in a metabolic profile. Systemic changes in pattern are indicative of specific states or of changes in status. This can be measured by quantifying the redox active components. Detecting and identifying subtle changes can be problematic with the sensitivity required to identify such molecules. New analytical technology addresses both problems using the central position of redox biochemistry in the biological process[8]

The general aim of metabolomics is to identify, measure and interpret the complex time-related concentration, activity and flux of endogenous metabolites in cells, tissues, and other biosamples such as blood, urine, and saliva. Metabolites such as small molecules that are the products and intermediates of metabolism, carbohydrates, peptides, and lipids vary in concentration, size, structure, polarity, and functional groups. An integrated set of technologies is needed to address the entire spectrum of metabolomics.[9]


Metabolomics in human blood

Mass spectrometry can now monitor enzymatic and hormonal regulation of thousands of metabolites by means of metabolomic techniques. The German Institute of Human Nutrition (DIFE) in cooperation with the Max-Planck Institute for molecular Genetics of Plants in Golm/potsdam and Metanomics in Berlin are adapting a plant analytic system for human tissue and plasma. A specific metabolite pattern in diabetes patients was possible to be identified. More detailed knowledge should allow the early identification of unfavorable metabolic profiles in order to develop preventive strategies.[10]

Plagemann revives the theory of Jean Baptiste Lamarck quoting that a high diabetes risk can be passed on to several generations. This is not caused by a genetic modification, but is due to an acquired condition. Experiments with rats have demonstrated that diabetes leads to an increased level of insulin in the unborn. The cells of the brain where the experience of hunger or satiety are located are irreversibly damaged and the production of insulin excessively secreted. Diabetes and overwight is therefore programed. [11].

Martin Pedersen, group leader of a nutrigenomics team of researchers from Denmark and Japan of Chr Hansen, said that a project analyses the genetic code of bacteria to improve probiotic food products within the four-year duration of the project. [2]


Supplementation during pregnancy

The mother's nutrition can be so important that it can alter her offspring's susceptibility to disease by changing gene expression, say researchers who claim to have explained for the first time how maternal nutrition can predetermine risk of obesity or cancer.

Scientists from Duke University in the US showed they could change the coat color of baby mice simply by feeding their mothers four common nutritional supplements before and during pregnancy

Dr Randy Jirtle, senior investigator of the study, published in today's issue of Molecular and Cellular Biology. "For the first time ever, we have shown precisely how nutritional supplementation to the mother can permanently alter gene expression in her offspring without altering the genes themselves." In experiments, pregnant mice thatreceived vitamin B12, folic acid, choline and betaine (from sugar beets) gave birth to babies predominantly with brown coats. In contrast, pregnant mice that did not receive the nutritional supplements gave birth predominantly to mice with yellow coats. The non-supplemented mothers were not deficient in these nutrients.

A study of the cellular differences between the groups of baby mice showed that the extra nutrients reduced the expression of a specific gene, called Agouti, to cause the coat color change. Yet the Agouti gene itself remained unchanged. This is called "DNA methylation", and it could potentially affect dozens of other genes that make humans and animals susceptible to cancer, obesity, diabetes, and even autism.

During DNA methylation a methyl group attaches to a gene at a specific point and alters its function. The methyl group silences the gene or reduces its expression inside a given cell, but does not actually change it. Such an effect is referred to as "epigenetic"

These changes occur early in embryonic development, before the mother would even be aware of the pregnancy. According to Dr. Jirtle, any environmental condition that impacts these windows in early development can result in developmental changes that are life-long, some of them beneficial and others detrimental. If such epigenetic alterations occur in the developing sperm or eggs,

Humans and other animals are susceptible to epigenetic changes because of an evolutionary trait in which "junk" remnants of viral infections, called "transposons," inserted themselves randomly within the human and animal genomes. If the transposons have inserted themselves in or near a functional gene, the gene can be inadvertently methylated, too, thereby reducing its expression.

More than 40 per cent of the human genome is comprised of transposons that are likely to be methylated, so any genes positioned near them could be at risk for inadvertent methylation. For example, methylation that occurs near or within a tumour suppressor gene can silence its anti-cancer activity, said Jirtle. Also they do not know which of the four nutrients caused methylation of the Agouti gene, revealing the uncertainty of nutrition's epigenetic effects on cells.

Methylating a single gene can also have multiple effects. For example, as well as changing coat color, mice that over-express the Agouti protein tend to be obese and susceptible to diabetes because the protein also binds with a receptor in the hypothalamus and interferes with the signal to stop eating. Methylating the Agouti gene in mice, therefore, also reduces their susceptibility to obesity, diabetes and cancer. The researchers stressed the importance of understanding the molecular effects of nutrition on cells, not just the outward manifestations of it.

Dr.Waterland says that diet, nutritional supplements and other seemingly innocuous compounds can alter the development in utero to such an extent that it changes the offspring's characteristics for life, and potentially that of future generations. Nutritional epigenetics could, for example, explain the differences between genetically identical twins, or the disparities in the incidence of stroke between the South and the North.

That is the reason why all supplements such as vitamines, minerals probiotics and a lot of other compounds should be analyzed carefully and nutrition should be kept as natural as possible.

A network of regulatory elements regulates cells [12] [13]

Professor John Mattick and colleagues performing the "FANTOM4" study found that there is a sophisticated network of regulatory elements that influence the expression of genes of the body. This opens the understanding on how cells transform from undifferentiated cells to mature cells with a specific function and explain why some cells turn cancerous and how stem cells may be used use in regenerative medicine.
Some results of the study are:


Tiny RNAs [14]

Tiny RNAs are 18 nucleotides long, 100 times smaller than an average gene and are the smallest genetic elements ever described. According to the authors tiny RNAs are associated with promoters that switch on genes, and have a role in gene activation, and may be used to artificially control gene expression.

Transposons [15]

Transposons are sequences of DNA that can move around to different positions within the genome of a single cell, a process called transposition. In the process, they can cause mutations and change the amount of DNA in the genome.

There are a variety of mobile genetic elements, and they can be grouped based on their mechanism of transposition.

Class I transposons

Class I mobile genetic elements, or retrotransposons, copy themselves by first being transcribed to RNA, then reverse transcribed back to DNA by reverse transcriptase, and then being inserted at another position in the genome.

Class II transposons

Class II mobile genetic elements move directly from one position to another using a transposase to "cut and paste" them within the genome.

Transposons were discovered by Barbara McClintock. She wrote that insertions, deletions, and translocations in the genome could, for example, lead to a change in the color of corn kernels. About 50% of the total genome of maize consists of transposons. The Ac/Ds system McClintock described are class II transposons.

Ac/Ds transposition in maize [16]

The maize Ac (Activator) and Ds (Dissociation) elements comprise a classical two component transposable element system of the hAT transposon family. Weber and colleagues present an animation showing the normal Ac element transposition process. http://jzhang.public.iastate.edu/transposition


Retrotransposons [17]

Retrotransposons are also called transposons via RNA intermediates and are a subclass of transposons. They are genetic elements that move around the genome and leave copies of themselves behind. Retrotransposons are only active in cancer cells and cells that turn into eggs and sperm, The authors noted that retrotransposons, which do not move around the genome any more, may still regulate the expression of nearby genes.


Transposons revealing gene functions [18]

Tian Xu and colleagues 2005 found how to switch on and off the expression of genes of the mouse genome to make it possible to study their functions. The researchers mutate each gene, to observe the resulting changes, revealing thus gene functions. Transposons, elements which can move from place to place in the DNA are used in these studies. Transposons allow material to be inserted or relocated.

Transposons have proved to be valuable genetic tools for many organisms, but not for vertebrates and mammals. Xu and colleagues used the transposon piggyBac from the cabbage looper moth in mouse and human cell lines. A red fluorescent protein and an enzyme changing the colour of a mouse from white to black was added to work as a marker. Expressions of the altered genes were inherited though five generations. The PiggyBac transposon can be removed from the next generation by breeding with a mouse bearing an enzyme which excises the transposon. The team of Xu is scaling up piggyBac for the Mouse Functional Genome Project.

The Mouse Functional Genome Project

The project tries to mutate the majority of mouse genes in China to understand the functions of the mammalian genes in context and to identify the causes of complex diseases having a genetic background in mammals The project aims to close the gap between genotype and phenotype studying the function of isolated proteins extended to their functional context in the cellular environment.

metabolomics

[19] Metabolomics is, according to a definition by Daviss, the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind". It is the study of their small-molecule metabolite profiles [20]. The metabolome represents the collection of all metabolites in a biological organism, which are the end products of its gene expression, and can give an instantaneous snapshot of the physiology of that cell.

New Terminology [21]

New terminology emerges with the new fields of science: omics refers fields in biology which have such a suffix genomics or proteomics, and omes referes to genome and proteome[], which is the entire complement of proteins expressed by a genome, cell, tissue or organism.

First metabolomics laboratory in UK will study the impact on health [22]

The laboratory will be maintained by the University of Birmigham, which believes that this new area of science will improve understanding of how pollutants can impact individuals and their health.

Beer protein research may improve brewing technology

[23]
Righetti and colleagues 2010 looked at the protein composition of beer which are important for the formation, texture, and stability of the of the beer foam, including 20 barley proteins, 40 proteins from yeast genes, and two proteins from corn. Saccharomyces cerevisiae, Saccharomyces bayanus and Saccharomyces pastorianus used in the malting process for lager beer were analysed and a widespread proteome of beer was established. Proteome is the entire set of proteins expressed by a genome, cell, tissue or organism.

The authors say that brewers may now use these findings to reduce off-flavour proteins or to increase flavour and texture improving proteins during the brewing process.

Comparative genomics identifies drug targets against fungal pathogens [24]

Abadio and colleagues 201, using comparative genomics, selected 10 genes present in pathogenic fungi which are absent in the human genome and may be used as anti-fungal drug target. The authors concentrated their researches on trr1 that encodes for thioredoxin reductase, rim8 that encodes for a protein involved in the proteolytic activation of a transcriptional factor in response to alkaline pH, kre2 that encodes for alpha-1,2-mannosyltransferase and erg6 that encodes for delta (24)-sterol C-methyltransferase. Drug side effects are not expected because these genes are not present in the human genome, stress the authors.

Metabolomics Society [25]

According to the Metabolomics Society metabolomics is a newly emerging field of "omics"[21] research concerned with the comprehensive characterization of the small molecule metabolites in biological systems. The Society believes that metabolomics can assess the metabolic status and global biochemical events associated with a cellular or biological system, and reveal both the physiological state of a cell or organism and of their responses to environment. UK, USA and Australia are the most active countries researching in metabolomics.

The European Nutrigenomics Organisation NuGO [26]

The European Nutrigenomics Organisation[] is a network linking genomics, nutrition and health research.

A key objective of the network will be the development, data warehousing and exploitation of nutrition and health-related bioinformatics for the benefit of European nutrition researchers, and for the community as a whole.

Genomics, a clinical decision support [27]

Bart De Moor et al., 2009 propose a kernel-based approach for clinical decision support in which many genome-wide data sources are combined using an As supervised classification algorithm, a weighted Least Squares Support Vector Machine.

The authors stress the importance of fusing more than one source of genome-wide data such as the genome, transcriptome, proteome, and epigenome linked by a methodological integration framework. The authors used this framework on a rectal cancer data set containing microarray and proteomics data and a prostate cancer data set containing microarray and genomics data. They noted the improving of the prediction of all outcomes when more than one genome-wide data set was considered.

The authors concluded that integrating multiple genome-wide data sources increases the predictive performance of clinical decision support models in patient tailored therapy.

The World Community Grid [28]

The aim of the community ist to provide computing power to studies in scientific field such as:
- New and existing infectious disease research - development of treatments for HIV/AIDS, Malaria, Severe Acute Respiratory Syndrome (SARS), etc.
- and disease - functions of proteins that are coded by human genes and how they might relate to cures for common diseases.
- Environmental research - meteorology and severe weather warning, pollution, remediation, climate modelling, and others.
- Natural disasters and hunger - earthquake warning, information on improving crop yields and livestock production, and evaluation of the supply of critical natural resources such as water.
Ongoing studies are:

The mission of Discovering Dengue Drugs - Togehther- [29]

The mission of Discovering Dengue Drugs - Together - is to identify promising drug candidates to combat the Dengue, Hepatitis C, West Nile, Yellow Fever, and other related viruses. These drugs target the viral NS3 protease, an enzyme critical for virus replication, and its amino acid sequence and atomic structure are very similar among the different disease-causing flaviviruses. In this study advanced structure-based computational drug discovery methods are used to identify small molecule protease inhibitors.

Malaria research and Plamodium Yoelii Yoelii [30]

The Bonneau Lab is working on microbiome projects such as analysing the malaria parasite Plasmodium Yoelii Yoelii. The team stresses that this rodent malaria parasite is important for understanding the function of human malaria.

Nanotechnology to improve filtration and desalination of water [31]

Scientists of the National Centre for Nano Science and Technology of the Chinese Academy hope optimize the process which will allow water to flow even more easily to filter and desalinate water using nanotubes.

The Human Microbiome Project [32]

A microbiome is the totality of microbes, their genetic elements (genomes), and environmental interactions in a defined environment. The microbiome usually includes microbiota and their complete genetic elements. Researchers in the Human Microbiome Project are sampling and analyzing the genome of microbes from five sites on the human body: nasal passages, oral cavities, skin, gastrointestinal tract, and urogenital tract. Microbiome studies the microorganisms included as part of the human genome, because of their influence on human physiology.

The Human Microbiome Project (HMP) is a United States National Institutes of Health initiative with the goal of identifying and characterizing the microorganisms which are found in association with both healthy and diseased humans (their microbial flora). This microbiome project is to test if changes in the human microbiome are associated with human health or disease. [33]

Gut microbiota symbiotic interaction with humans

Khoruts and Sadowsky 2011 report an example of the importance of gut microbiota and interaction with its host. The authors report treatment of Clostridium difficile gut infections with foecal transferes after collapse of the microbial community caused by antibiotic therapy or infection with pathogen. A better understanding of the interactions of humans with bacteria and synergistic are expected to result of these studies. [34]

According to Laparra and Sanz 2010 the beneficial effects of prebiotics mainly relay on their influence on the gut microbiota composition and their ability to generate fermentation products which may improve the status of immunity and metabolism of the host. The gut microbiota enhance the antioxidant effects of polyphenols transforming them in bioavailable compounds. Prebiotics may stimulate beneficial bacteria inhibiting pathogenic strains. The modulation of the intestinal microbiota can be used to treat intertinal disfunctions and may enhance the biological activity of micronutrients.based on the interactions of gut bacteria on human health. [35]

Roberfroidet al 2010 define as 'normobiosis' the composition of the gut 'ecosystem' in which micro-organisms with potential health benefits predominate in number over potentially harmful ones, in contrast to 'dysbiosis', in which one or a few potentially harmful micro-organisms are dominant, thus creating a disease-prone situation. The authors concluded that prebiotics may cause a selective modification in the composition of the gut microbiota leading to normobiosis could either induce beneficial physiological effects or reducing the risk of dysbiosis and associated intestinal and systemic pathologies. [36]


Soil metagenome [37]

The composition of soil microbiological population is complex. Metagenomics, the study of the entire genome of soil biota, provide a tool to discover new species, genes or novel molecules that are relevant for biotechnology and agricultural applications.

Assessing the microbiological population of soil and sediments encounters difficulties as most of the microorganisms in nature are uncultivable. Soil metagenome are suggested to study the genetic resources from terrestrial environments. Rajendhran and Gunasekaran 2008 stress that methods are being developed for a direct isolation of environmental DNAs which are cloneable and can be used in genomic DNA libraries with subsequent high-throughput sequencing or library screening. [38]

Metagenomics of disease-suppressive soils [39]

van Elsas et al. 2008 describe molecular tools to assess the collective soil metagenome as an alternative to cultivation. The authors aim to explore genes of biotechnological interest, such as the metagenome of disease-suppressive soils with antibiotic biosynthetic clusters. The author highlights the help of the disease-suppressive soils project METACONTROL to handle the high amount of data of soil metagenome.

Reigstad at al 2011 point out that metagenomics the metabolisms from rather uninvestigated organisms such as the ammonia-oxidizing archaea. For that methods were used to isolate high-molecular weight (hmw) DNA from soil and hot spring samples and mud, produce large-insert metagenomic libraries, analyse the resulting genomic fragments, and screen the libraries for genes of interest. [40]

Crop plants are more resistant to diseases growing on certain soils compared to other soils. This may be linked to exceptional ecosystems where the community of microbes inhibits root pathogens, such as certain moulds.

Mendes and colleagues 2011 identified more than 33,000 bacterial and archaeal species and genes which are linked to inhibition of pathogens using PhyloChip-based metagenomics, together with culture-dependent functional analyses. The authors report that Proteobacteria, Firmicutes, and Actinobacteria, and nonribosomal peptide synthetases of gama-Proteobacteria were linked to disease suppressionwere shown to have disease-suppressive activity governed by. [41]

High molecular weight genomic DNA extraction [42]

Lee and Hallam present a protocol for extracting high molecular weight, microbial community genomic DNA from soils and sediments suitable for constructing large insert environmental genomic libraries..This protocol uses mechanical grinding and beta-mercaptoethanol for cell lysis.

Chloroform-isoamyl alcohol and isopropyl alcohol is used to isolate the genomic DNA, together with guanidine isothiocyanate and hexadecyltrimethylammonium bromide as buffer. To reduce impurities such as proteins and humic acids, the isolated genomic DNA can be further purified using cesium chloride (CsCl). The whole process takes two and a half days, therefore shearing, severe vortexing and harsh pipetting should be avoided in order to prevent damage of the DNA.


Blood serum metagenomic analysis may predict future development of Alzheimer's Disease years ahead of the first symptoms [43]

According to a study of Orešič et al 2011, blood serum analysis may predict future development of Alzheimer's Disease (AD) before symptoms of the disease occur. The analysis identifies molecular changes associated with Alzheimer Disease years in advance. These biomarkers suggest a state of increased hypoxia.

The authors explain that mild cognitive impairment (MCI) is a transition phase between normal aging and Alzheimer's disease. MCI increases the risk of Alzheimer's disease, but has several possible outcomes, including even improvement back to normal cognition.

The metabolomic research on changes in lipids related to the disease detect small metabolites blood profile used as a good predictive markers.

The authors stress that AD patients were characterized by diminished ether phospholipids, phosphatidylcholines, sphingomyelins, and sterols.

The molecular signature of the MCI patients progressing to AD is leaded by 2,4-dihydroxybutanoic acid as an indicated the potential involvement of hypoxia. The pentose phosphate pathway also causes hypoxia and oxidative stress plays a role in early stage of AD.

Dr. Orešič and colleagues point out that reduction of several membrane phospholipids in patients serum, contrary to foregoing studies, could not be seen as early predictors of Alzheimer`s Disease, but may be a later event. The authors suggest, therefore, to see hypoxia as early predictor of AD instead of lipid-changes.

Other approach of early markers for Alzheimer's Disease [44]

Other approaches to a early diagnosis of AD were such as the study of Li et al. 2010 aiming to was map potential biomarkers in plasma. using ultra performance liquid chromatography/mass spectrometry (UPLC/MS) and metabonomics approach. The principal component analysis (PCA) of UPLC/MS spectra showed that metabolic changes between two groups. The authors report nine potential biomarkers in correlation with the extent of AD, such as lysophosphatidylcholines LPCs, sphingosine and tryptophan may be potential early markers of the disease.

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