Metabolomics : A Promising Tool in Health Resesarch
Dr. Anna Artati, M.Sc
Metabolomics is the science of metabolism in organisms. Metabolomics is the
systematic study of the small molecular metabolites in a cell, tissue, biofluid, or cell culture media that are the tangible result of cellular processes or responses to an environmental stress. The metabolome is the total complement of metabolites present in a biological sample under given genetic, nutritional or environmental conditions. metabolomics affords detailed characterization of metabolic phenotypes and can enable precision medicine at a number of levels, including the characterization of metabolic derangements that underlie disease, discovery of new therapeutic targets, and discovery of biomarkers that may be used to either diagnose disease or monitor activity of therapeutics. Metabolomics technologies yield many insights into basic biological research in areas such as systems biology and metabolic modelling, pharmaceutical research, nutrition and toxicology. Application of Metabolomics : 1. Health as a biomarker to find out certain diseases 2. Toxicology, in plants, agriculture 3. Pharmacy (Drug delivery) 4. Environment Maximum coverage and elucidation of the metabolome’s chemical space can be achieved by utilizing HPLC or UPLC, LC-MS, GC-MS, and NMR systems in conjunction with dedicated software for data evaluation. The advantage of metabolomics is, the samples analyzed non-impassively are urine, blood, etc, where people do not experience pain. The general approach to metabolomics includes non targets and targets. a. Non target Nontargeted metabolomics is a comprehensive analytic approach that attempts to detect, identify, and relatively quantify as many metabolites in a biological sample as possible. In doing so, nontargeted approaches aim to discriminate unique metabolite features associated with a genotype, pharmacological treatment, clinical subpopulation, or other comparative grouping, usually by comparison to appropriate control groups. Major challenges of non-targeted metabolomics include metabolite identification of unknown spectral features, which requires established or in-house metabolite databases, lack of reliable fragmentation chemistries for all biomolecules of interest, and chemical/biochemical modification of metabolites resulting in spectral shifts. Nevertheless, the wide coverage provided by nontargeted approaches has the potential to identify novel metabolic pathways, disease biomarkers, and drug-derived metabolites. To apply nontargeted metabolomics to human disease cohorts, which can involve hundreds to thousands of samples, careful design of workflow is required to maintain reproducibility within and between analytic batches. b. Target In targeted metabolomics, a selective group of metabolites often clusters of chemically related analytes are measured with tailored analytic approaches for absolute quantification. A major benefit of targeted techniques is increased sensitivity and selectivity, because metabolite extraction, compound separation (if desired), and instrumentation parameters can be optimized to develop quantitative metabolite panels. This is in contrast to nontargeted metabolomics, where metabolites are presented by methods of relative quantification, typically involving peak area comparison of the analytes of interest. The genetic connection with metabolomics is metabolism is a bridge that connects compounds I and other compounds that cause a certain illness. Genetics affects a person's condition, but many other factors that affect such as food consumed, activities, sports, and lifestyle. Everyone has different metabolites. Genetic and metabolic affect each other. Genetic variation will be associated with various diseases in the organism. Metabolomics is an intermediate to determine the mechanism of disease with environmental factors. In populations there is genetic variation, there are people who have homozygous or heterozygous carrier genes. For example, the FADS gene is related to acid metabolism. Genetic variation shows that everyone has a different metabolic profile. The role of metabolites in health, namely metabolomics, has great potential to define new biomarkers of diabetes, cardiovascular resistance, stroke, etc. a. Diabetes Diabetes represents one of the most important global health problems because it is associated with a large economic burden on the health systems of many countries. With the development of metabolomics, it is expected to achieve a more personalized control of diabetes. Depending on the patient’s metabolomic profile, it would be possible to perform more effective strategies with personalized decisions based on the individual behavior, phenotypic features, laboratory findings, gene sequences, and metabolic and proteomic profiles. The late advances in the field of omics offer new opportunities to improve early diagnosis, clinical outcome, prevention of complications, and decrease in disease progression. The application of metabolomics in diabetes studies has rapidly evolved during the last decade and provides researchers the opportunity to gain new insights into metabolic profiling and pathophysiological mechanisms. Thus, several metabolites were identified to be related to diabetes or insulin resistance and represent the basis for the identification of novel diabetes biomarkers. Some findings were newly discovered altered metabolites, e.g. bile acids, whereas other metabolic variations were already known, e.g. fatty acids or amino acids. The potential of an amino acid profile as a predictor and highlighted the fact that the addition of amino acids to established risk factors only minimally improved the risk predication. This general problem is also apparent for genetic variants and other clinical novel biomarkers of diabetes whose power to add considerable improvement in risk assessment is limited. Nevertheless, metabolomics increases the knowledge of disease progression and provides approaches for therapy. The presence of metabolomics shows that some amino acids can function as a marker of diabetes, for example certain amino acids are high, it is likely to experience diabetes. The concentration of aromatic compounds high, is the possibility of developing diabetes. b. Cadiovascular One important application of metabolomics is the discovery of novel biomarkers of cardiovascular disease. Metabolomics, one of the newer omics technologies, has emerged as a powerful tool for defining changes in both global and cardiac-specific metabolism that occur across a spectrum of cardiovascular disease states. Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. Metabolic program aims to understand how blood vessels function, both normally and under pathologic conditions. Utilizing a range of techniques, including molecular studies, cells grown in tissue culture, isolated blood vessels, intact animal models, and human metabolomics and genomics. metabolomics can be identifying novel therapies for cardiovascular disease. In a study showing Phenylalanine and mono unsatura poly acid are positively associated with cardiovascular development, so they are at high risk of cardiovascular disease. Omega 6 and DHA are negatively associated with cardiovascular development. Digestion can affect the metabolic cycle, thus affecting health. Metabolomics steam cell research, steam cell, is a cell that will develop into a variety of cells. Steam cells can be made from adult cells, skin, red blood cells. Adult cells capable of being steam cells can then be converted into heart cells, liver cells, etc. The metabolomic role as a marker, whether or not the compound causes a disease. Advantages of iPSC are iPSCs can be created from the tissue of the same patient that will review the transplantation, thus avoiding immune rejection, lack of ethical implications because cells are harvested from a willing adult without harming them, these patient specific cells can be used to study diseases in vitro, to test drugs on a human model without endangering anyone, and to hopefully act as tissue replacement for diseased and damaged cells. References Artati, A., Prehn, C., Möller, G., & Adamski, J. (2012). Assay tools for metabolomics. In Genetics Meets Metabolomics (pp. 13-38). Springer, New York, NY. Clish, C. B. (2015). Metabolomics: an emerging but powerful tool for precision medicine. Molecular Case Studies, 1(1), a000588. Friedrich, N. (2012). Metabolomics in diabetes research. Journal of Endocrinology, 215(1), 29-42. McGarrah, R. W., Crown, S. B., Zhang, G. F., Shah, S. H., & Newgard, C. B. (2018). Cardiovascular metabolomics. Circulation Research, 122(9), 1238-1258.