Metabolomics, Metabonomics and Functional Nutrition: The Next Step in Nutritional Metabolism and Biotherapeutics
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Keywords

 Genomics, Functional genomics, Proteomics, Metabolic Pathways, Metabolome, Metabonomics, Metabolic Syndrome, Inflammatory Process, Cancer, Iron Metabolism, Obesity, Fat Metabolism

How to Cite

Larry H. Bernstein. (2012). Metabolomics, Metabonomics and Functional Nutrition: The Next Step in Nutritional Metabolism and Biotherapeutics. Journal of Pharmacy and Nutrition Sciences, 2(1), 1–14. https://doi.org/10.6000/1927-5951.2012.02.01.1

Abstract

Metabonomics is the newest member of the convergent "-omics" family. This multi-parametric technique is used for studying metabolites in biological fluids for the purpose of metabolic profiling for biomarker and diagnostic applications, and to study the effects of environmental stimuli (diet, weight loss, exercise) and other therapeutic applications (lifestyle modification and drug effects) on the metabolome. Metabonomics has the advantage for defining biological phenotypes, but has a close relationship to investigation of the proteome, driven by advances in NMR and MS. The technique has proved highly informative in applications that include toxicology, pharmacology, and the biomedical sciences. This review elaborates on the paradigm shift that is emerging from this discovery process.

https://doi.org/10.6000/1927-5951.2012.02.01.1
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References

Trujillo E, Davis C, Milner J. Nutrigenomics, proteomics, metabolomics, and the practice of dietetics. J Am Diet Assoc 2006; 106(3): 403-13. http://dx.doi.org/10.1016/j.jada.2005.12.002

Kussmann M, Raymond F, Affolter M. OMICS-driven biomarker discovery in nutrition and health. J Biotechnol 2006; 124(4): 758-87. http://dx.doi.org/10.1016/j.jbiotec.2006.02.014

Zeisel SH. Nutrigenomics and metabolomics will change clinical nutrition and public health practice: insights from studies on dietary requirements for choline. Am J Clin Nutr 2007; 86(3): 542-8.

García-Cañas V, Simó C, León C, Cifuentes A. Advances in Nutrigenomics research: novel and future analytical approaches to investigate the biological activity of natural compounds and food functions. J Pharm Biomed Anal 2010; 51(2): 290-304. http://dx.doi.org/10.1016/j.jpba.2009.04.019

Kussmann M, Blum S. OMICS-derived targets for inflammatory gut disorders: opportunities for the development of nutrition related biomarkers. Endocr Metab Immune Disord Drug Targets 2007; 7(4): 271-87. http://dx.doi.org/10.2174/187153007782794317

Ovesná J, Slaby O, Toussaint O, et al. High throughput 'omics' approaches to assess the effects of phytochemicals in human health studies. Br J Nutr 2008; 99(E Suppl 1): ES127-34.

Workshop Report: “The 2010 Project”. Chory J, Ecker JR, Briggs S, et al. A Blueprint for Understanding How Plants Are Built and How to Improve Them. Plant Physiology 2000; 123: 423-425. www.plantphysiol.org.

Consensus Report. Board on Healthcare Services. Review of Omics-Based Tests for Predicting Patient Outcomes in Clinical Trials. Evolution of Translational Omics: Lessons Learned and the Path Forward. March 23, 2012.

Stover PJ, Caudill MA. Genetic and epigenetic contributions to human nutrition and health: managing genome-diet interactions. J Am Diet Assoc 2008; 108(9): 1480-7. http://dx.doi.org/10.1016/j.jada.2008.06.430

Kussmann M, Panchaud A, Affolter M. Proteomics in nutrition: status quo and outlook for biomarkers and bioactives. J Proteome Res 201; 9(10): 4876-87.

Wolfram Weckwerth. Metabolomics in Systems Biology. Ann Rev Plant Biol 2003; 54: 669-89. http://dx.doi.org/10.1146/annurev.arplant.54.031902.135014

Kussmann M, Affolter M, Nagy K, Holst B, Fay LB. Mass spectrometry in nutrition: understanding dietary health effects at the molecular level. Mass Spectrom Rev 2007; 26(6): 727- 50. http://dx.doi.org/10.1002/mas.20147

Freyhult E, Prusis P, Lapinsh M, Wikberg JES, Moulton V, Gustafsson MG. Unbiased descriptor and parameter selection confirms the potential of proteochemometric modelling. BMC Bioinformatics 2005, 6: 50. http://dx.doi.org/10.1186/1471-2105-6-50

Börsbo B, Gerdle B, Peolsson M. Impact of the interaction between selfefficacy, symptoms and catastrophizing on disability, quality of life and health in chronic pain patients. Disability Rehabilitation 2010; 17(32): 1387-1396. http: //dx.doi.org/10.3109/09638280903419269 Copyright: Informa Healthcare http: //informahealthcare.com/Postprint available at: Linköping University Electronic Press http: //urn.kb.se/resolve?urn=urn: nbn: se: liu: diva-15690

Grainger DJ. Megavariate Statistics meets High Data-density Analytical Methods: The Future of Medical Diagnostics? IRTL Reviews 2003; 1: 1-6.

Magidson J. Regression Modeling and Classification with Many Correlated Predictors: Key Driver Regression and Other Applications Using CCR Methods. SI online course. Session 1. Jan 13-20. Cross-validation: Assessing/Validating model performance with and without cut-points; Holdout samples and M-fold cross-validation; Generalizability and R2; Repeated rounds of M-folds.

Rypka EW. Methods to evaluate and develop the decision process in tests. In Nakamura R. ed. Clinics in Laboratory Medicine. Phila., PA. WB Saunders 1992; 12(2): 351-86.

Kullback S, Liebler RA. On information and sufficiency. Ann Math Statist 1951; 38(22): 79-86. http://dx.doi.org/10.1214/aoms/1177729694

Akaike H. Information theory as an extension of the maximum likelihood principle. In BN Petrov and F Csaki, Eds. Second International Symposium on Information Theory. Akdemiai Kiado, Budapest 1973; pp. 267-281.

Fisher RA. On the Mathematical Foundations of Theoretical Statistics. Philosophical Trans Royal Soc Lond A 1922; 222: 309-68. http://dx.doi.org/10.1098/rsta.1922.0009

Rudolph RA, Bernstein LH, Babb J. Information induction for predicting acute myocardial infarction. Clin Chem 1988; 34: 2031-8.

David G, Bernstein L, Coifman RR. Generating evidence based interpretation of hematology screens via anomaly characterization. Open Clin Chem J 2011; 4: 101-6. http://dx.doi.org/10.2174/1874241601104010010

DeBusk R. The Role of Nutritional Genomics in Developing an Optimal Diet for Humans. Nutr in Clin Pract 2010; 25(6): 627-633. © 2010. (10.1177/0884533610385700 http: //ncp.sagepub.com. http: //online.sagepub.com)

Bell JK, Mullen GE, Leifer CA, Mazzoni A, Davies DR, Segal DM. Leucine-rich repeats and pathogen recognition in Tolllike receptors. Trends Immunol 2003; 24: 528-33. http://dx.doi.org/10.1016/S1471-4906(03)00242-4

Pritz JH, et al. Nod-like proteins in immunity, inflammation and diseases. Nat Immunol 2006; 7: 1250-57. http://dx.doi.org/10.1038/ni1412

Kanneganti T-D, Lamkanfi M, Nunez G. Intracellular NODlike receptors in Host Defense and Disease. Immunity 2007; 27: 549-59.

Creagh EM, O’Neill LAJ. TLRs, NLRs, and RLRs: a trinity of pathogen sensors that cooperate in innate immunity. Trends Immunol 27: 352-57. http://dx.doi.org/10.1016/j.it.2006.06.003

McGonagle D, Savic S, McDermott MF. The NLR network and the immunological disease continuum of adaptive and innate immune-mediated inflammation against self. Semin Immunopathol 2007; 29: 303-13. http://dx.doi.org/10.1007/s00281-007-0084-1

Corella D, Ordovas JM. Nutrigenomics in cardiovascular medicine. Circ Cardiovasc Genet 2009; 2: 637-51. http://dx.doi.org/10.1161/CIRCGENETICS.109.891366

Corella D, Ordovas JM. Single nucleotide polymorphisms that influence lipid metabolism: interaction with dietary factors. Annu Rev Nutr 2005; 25: 341-90. http://dx.doi.org/10.1146/annurev.nutr.25.050304.092656

Seeberg E, Eide L, Bjørås M. The base excision repair pathway. Trends Biochem Sci 1995; 20(10): 391-97. http://dx.doi.org/10.1016/S0968-0004(00)89086-6

Booth MJ, Branco MR, Ficz G, Oxley D, Krueger F, Reikhttp: //www.sciencemag.org/content/336/6083/934 - corresp-1 W, et al. Quantitative Sequencing of 5-Methylcytosine and 5- Hydroxymethylcytosine at Single-Base Resolution. Science 2012; 336(6083): 934-937. DOI: 10.1126/science.1220671; Pub Online April 26 2012.

Pereira J, Ralston C, Douglas N, et al., Mechanism of nucleotide sensing in group II Chaperonins. EMBO J 2012; 31: 731-740. http://dx.doi.org/10.1038/emboj.2011.468

Torres DA, Azagarsamy MA, Thayumanavan S. Supramolecular Displacement-Mediated Activation of a Silent Fluorescence Probe for Label-Free Ligand Screening. J Am Chem Soc 2012; 134(17): 7235-37. DOI: 10.1021/ ja301204z

Heiss; C, Keen CL, Kelm M. Flavanols and Cardiovascular Disease Prevention. Eur Heart J 2010; 31(21): 2583-92.

Kussmann M, Rezzi S, Daniel H. Profiling techniques in nutrition and health research. Curr Opin Biotechnol 2008; 19(2): 83-99. http://dx.doi.org/10.1016/j.copbio.2008.02.003

Ohashi N, Ito C, Fujikawa R, et al. The impact of visceral adipose tissue and high-molecular weight adiponectin on cardia-ankle vascular index in asymptomatic Japanese subjects. Metabolism 2009; 58: 1023-9.

Zha JM, Di WJ, Zhu T, et al. Comparison of gene transcription between subcutaneous and visceral adipose tissue in chinese adults. Endocr J 2009; 56: 934-44.

Albert L, Girola A, Gilardini L, et al. Type 2 diabetes and metabolic syndrome are associated with increased expression of 11 beta-hydroxysteroid dehydrogenase 1 in obese subjects. Int J Obesity (Lond) 2007; 31: 1826-31. http://dx.doi.org/10.1038/sj.ijo.0803677

Fabbrini E, Markos F, Mohammed BS, et al. Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. PNAS 2009; 106: 15430-5. http://dx.doi.org/10.1073/pnas.0904944106

Tong J, Boyko EJ, Utzschneider KM, et al. Intraabdominal fat accumulation predicts the development of the metabolic syndrome in non-diabetic Japanese-Americans. Diabetologia 2007; 50: 1156-60. http://dx.doi.org/10.1007/s00125-007-0651-y

Kim K, Valentine RJ, Shin Y, Gong K. Association of visceral adiposity and exercise participation with C- reactive protein, insulin resistance, and endothelial dysfunction in Korean healthy adults. Metabolism 2008; 57: 1181-9.

Villaret A, Galitzky J, Decaunes P, et al. Adipose tisue endothelial cells from obese human subjects: differences among depots in angiogenic, metabolic, and inflammatory gene expression and cellular senescence. Diabetes 2010; 59: 2755-63. http://dx.doi.org/10.2337/db10-0398

van Dijk -, Feskens EJ, Bos MB, et al. A saturated fatty acidrich diet induces an obesity-linked proinflammatory gene expression profile in adipose tissue of subjects at risk of metabolic syndrome. Am J Clin Nutr 2009; 90: 1656-64.

Theurl I, Aigner E, Theurl M, et al. Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications. Blood 2009; 113(21): 5277-86. http://dx.doi.org/10.1182/blood-2008-12-195651

Cheng PP, Jiao XY, Wang XH, Lin JH, Cai YM. Hepcidin expression in anemia of chronic disease and concomitant iron-deficiency anemia. Clin Exp Med 2010;

Spratlin JL, Serkova NJ, Eckhardt SG. Clinical Applications of Metabolomics in Oncology: A Review. Clin Cancer Res 5(2): 431–440.

Fischer PM, Lane DP. Small molecule inhibitors of thep53 suppressor HDM2: have protein-protein interactions come of age as drug targets? Trends in Pharm Sci 2004; 25(7): 343- 46. http://dx.doi.org/10.1016/j.tips.2004.04.011

Visser M, Bouter LM, McQuillan GM, Wener HM. Elevated CReactive Protein Levels in Overweight and Obese Adults. JAMA 1999; 282: 2131-35. http://dx.doi.org/10.1001/jama.282.22.2131

Yudkin JS, Stehouwer CDA, Emeis JJ, Coppack SW. C-Reactive Protein in Healthy Subjects: Associations With Obesity, Insulin Resistance, and Endothelial Dysfunction: A Potential Role for Cytokines Originating From Adipose Tissue? Arterioscler. Thromb. Vasc. Biol. 1999; 19: 972-78. http://dx.doi.org/10.1161/01.ATV.19.4.972

Visvikis-Siest S, Siest G. The STANISLAS cohort: a 10-year followup of supposed healthy families. Gene-environment interactions, reference values and evaluation of biomarkers in prevention of cardiovascular diseases. Clin Chem Lab Med 2008; 46: 733-47. http://dx.doi.org/10.1515/CCLM.2008.178

Schmidt MI, Duncan BB. Diabesity: an inflammatory metabolic condition. Clin Chem Lab Med 2003; 41: 1120-30. http://dx.doi.org/10.1515/CCLM.2003.174

dos Santos MM, Gombert AK, Christensen B, Olsson L, Nielsen J. Identification of in vivo enzyme activities in the cometabolism of glucose and acetate by Saccharomyces cerevisiae using 13C-labeled substrates. Eukaryot Cell 2003; 2: 599-608. http://dx.doi.org/10.1128/EC.2.3.599-608.2003

Fenkci S, Rota S, Sabir N, Akdag B. Ultrasonographic and biochemical evaluation of visceral obesity in obese women with non-alcoholic fatty liver disease. Eur J Med Res 2007; 12: 68-73. (VAT, HOMA)

Lee JW, Lee HR, Shim JY, et al. Viscerally obese women with normal body weight have greater brachial-ankle pulse wave velocity than non viscerally obese women with excessive body weight. Clin Endocrinol (Oxf) 2007; 66: 572- 8.

Kaysen GE. The Microinflammatory State in Uremia: Causes and Potential Consequences. J Am Soc Nephrol 2001; 12: 1549-57.

Kaysen GE. Role of Inflammation and Its Treatment in ESRD Patients. Blood Purif 2002; 20: 70-80. http://dx.doi.org/10.1159/000046988

Bar-Or D, Thomas GW, Yukl RL, et al. Copper stimulates the synthesis and release of interleukin-8 in human endothelial cells: a possible early role in systemic inflammatory responses. Shock 2003; 20(2): 154-58. http://dx.doi.org/10.1097/01.shk.0000068318.49350.3a

Dugina TN, Kiseleva EV, Chistov IV, Umarova BA, Strukova SM. Receptors of the PAR Family as a Link between Blood Coagulation and Inflammation. Biochemistry (Moscow), 2002; 67(1): 65-74.

Monaco C, Andreakos E, Kiriakidis S, Feldmann M, Ewa Paleolog. T-Cell-Mediated Signalling in Immune, Inflammatory and Angiogenic Processes: The Cascade of Events Leading to Inflammatory Diseases. Curr Drug Targets - Inflammation & Allergy 2004; 3: 35-42. http://dx.doi.org/10.2174/1568010043483881

Monaco C, Grosjean J, and Paleolog E. The role of the NF?B pathway in atherosclerosis.

Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002; 105: 1135-43. http://dx.doi.org/10.1161/hc0902.104353

Karin M, Yamamoto Y, Wang QM. The IKK NF-kappa B system: a treasure trove for drug development. Nat Rev Drug Discov 2004; 3: 17-26. http://dx.doi.org/10.1038/nrd1279

Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-[kappa

Ingenbleek Y. The Oxidative Stress OF Hyperhomocysteinemia Results from Reduced Bioavailability of Sulfur- Containing Reductants. Open Clin Chem J 2011; 4: 34-44. http://dx.doi.org/10.2174/1874241601104010034

Ingenbleek Y, McCully KS. Vegetarianism produces subclinical malnutrition, hyperhomocysteinemia and atherogenesis. Nutrition 2011; 21872435.

Elshorbagy AK, Valdivia-Garcia M, Refsum H, Smith AD, Mattocks DAL, Perrone CE. Sulfur amino acids in methionine-restricted rats: Hyperhomocysteinemia. Nutrition. 2010 Jan 15; 20080389 (marked reduction in serum concentrations of methionine, cystathionine, cysteine, and taurine in methionine-restricted rats).

Ingenbleek Y. Hyperhomocysteinemia is a biomarker of sulfur-deficiency in human morbidities. Open Clin Chem J 2009; 2: 49-60. http://dx.doi.org/10.2174/1874241600902010049

Sen U, Givvimani S, Abe OA, Lederer ED, Tyagi SC. Cystathionine ?-synthase and cystathionine ?-lyase double gene transfer ameliorate homocysteine-mediated mesangial inflammation through hydrogen sulfide generation. Am J Physiol Cell Physiol 2011; 300(1): C155-C163. http://dx.doi.org/10.1152/ajpcell.00143.2010

Ingenbleek Y. The nutritional relationship linking sulfur to nitrogen in living organisms. J Nutr 2006; 136(6): 1641S-51S. 16702334.

Lee DY, Bowen BP, Northen TR. Mass spectrometry–based metabolomics, analysis of metabolite-protein interactions, and imaging. BioTechniques 2010; 49: 557-65. http://dx.doi.org/10.2144/000113451

Faca V, Krasnoselsky A, and Hanash S. Innovative proteomic approaches for cancer biomarker discovery. Biotechniques 2007; 43(3): 279, 281-3, 285. http://dx.doi.org/10.2144/000112541

Sharp P, and MIT faculty. 'Convergence' offers potential for revolutionary advance in biomedicine. The Third Revolution: Convergence of the Life Sciences, Physical Sciences and Engineering. White paper. Reported in Biotechnology Jan 5, 2011.

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