Metabolomic profiles as a new understanding of disease processes
https://doi.org/10.22416/1382-4376-2022-32-1-46-52
Abstract
Aim. This review will demonstrate possibilities of using metabolomic profiling to identify biomarkers of various internal organs diseases.
Key points. A new diagnostic direction is associated with high-sensitive spectral analysis of biomarker molecules. This review will discuss some of the latest advances with an emphasis on the use of metabolomics to identify major metabolic changes in various diseases. The possibility of finding diagnostic markers in diseases of the gastrointestinal tract, respiratory and cardiovascular systems, in oncology, endocrinology, neurology are discussed. These results define new potential therapeutic strategies, making metabolomics useful for a wide range of biomedical and pharmaceutical research.
Conclusion. Metabolomic profile changes in different types of diseases will help to improve understanding of the pathogenesis. New therapeutic approaches may be developed. They will take into account individual characteristics of the patient, identified by using current molecular technologies. The results of metabolomic studies can be used to monitor treatment outcomes.
About the Authors
O. Yu. Zolnikova
Sechenov First Moscow State University (Sechenov University)
Russian Federation
Russian Federation
Oxana Yu. Zolnikova — Dr. Sci. (Med.), Associate Prof., Department of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology, I.M. Sechenov First Moscow State Medical University (Sechenov University).
119435, Moscow, Pogodinskaya str., 1, bld. 1.
M. S. Reshetova
Sechenov First Moscow State University (Sechenov University)
Russian Federation
Russian Federation
Maria S. Reshetova — graduate student, Department of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology, I.M. Sechenov First Moscow State Medical University (Sechenov University).
119435, Moscow, Pogodinskaya str., 1, bld. 1.
M. N. Ivanova
Sechenov First Moscow State University (Sechenov University)
Russian Federation
Russian Federation
Marina N. Ivanova — graduate student, Department of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology, I.M. Sechenov First Moscow State Medical University (Sechenov University).
119435, Moscow, Pogodinskaya str., 1, bld. 1.
V. T. Ivashkin
Sechenov First Moscow State University (Sechenov University)
Russian Federation
Russian Federation
Vladimir T. Ivashkin — Dr. Sci. (Med.), RAS Academician, Prof., Department Head, Department of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology, I.M. Sechenov First Moscow State Medical University (Sechenov University).
119435, Moscow, Pogodinskaya str., 1, bld. 1.
References
1. Wishart D. Emerging applications of metabolomics in drug discovery and precision medicine Nat Rev Drug Discov. 2016;15(7):473–84. DOI: 10.1038/nrd.2016.32
2. van de Velde B., Guillarme D., Kohler I. Supercritical fluid chromatography — Mass spectrometry in metabolomics: Past, present, and future perspectives. J Chromatogr B Analyt Technol Biomed Life Sci. 2020;1161:122444. DOI: 10.1016/j.jchromb.2020.122444
3. Kelly R.S., Kelly M.P., Kelly P.Т. Metabolomics, physical activity, exercise and health: A review of the current evidence. Biochim Biophys Acta Mol Basis Dis. 2020;1866(12):165936. DOI: 10.1016/j.bbadis.2020.165936
4. Ghosh T., Philtron D., Zhang W., Kechris K., Ghosh D. Reproducibility of mass spectrometry based metabolomics data. BMC Bioinformatics. 2021;22(1):423. DOI: 10.1186/s12859-021-04336-9
5. Kondoh H., Kameda M., Yanagida M. Whole Blood Metabolomics in Aging Research. Int J Mol Sci. 2020;22(1):175. DOI: 10.3390/ijms22010175
6. Ma C., Tian B., Wang J., Yang G., Pan C., Lu J. Metabolic characteristics of acute necrotizing pancreatitis and chronic pancreatitis. Mol Med Rep. 2012;6(1):57–62. DOI: 10.3892/mmr.2012.881
7. Díaz C., Jiménez-Luna C., Diéguez-Castillo C. Untargeted metabolomics for the diagnosis of exocrine pancreatic insufficiency in chronic pancreatitis. Med. 2021;57(9):1–9. DOI: 10.3390/medicina57090876
8. Franzosa E.A., Sirota-Madi A., Avila-Pacheco J. Gut microbiome structure and metabolic activity in inflammatory bowel disease. Nat Microbiol. 2019;4(2):293–305. DOI: 10.1038/s41564-018-0306-4
9. Gallagher K., Catesson A., Griffin J., Holmes E., Williams H. Metabolomic Analysis in Inflammatory Bowel Disease: A Systematic Review. 2021;15(5):813–26. DOI: 10.1093/ecco-jcc/jjaa227
10. Sitkin S.I., Tkachenko E.I., Vakhitov T.Ya., Oreshko L.S., Zhigalova T.N., Avalueva E.B. Serum metabolome and intestinal microbiota in ulcerative colitis and celiac disease. Bulletin of the North-Western State Medical University named after I.I. Mechnikov. 2014;3:12–23 (In Russ.).
11. Masarone M., Troisi J., Aglitti A., Torre P., Colucci A., Dallio M. Untargeted metabolomics as a diagnostic tool in NAFLD: discrimination of steatosis, steatohepatitis and cirrhosis. Metabolomics. 2021;17(2):12. DOI: 10.1007/s11306-020-01756-1
12. Nimer N., Choucair I., Wang Z., Nemet I., Li L., Gukasyan J. Bile acids profile, histopathological indices and genetic variants for non-alcoholic fatty liver disease progression. Metabolism. 2020; 116:154457. DOI: 10.1016/j.metabol.2020.154457
13. Anokhina T.N., Anaev E.Kh., Chuchalin A.G., Revelsky A.I., Rodionov A.A., Revelsky I.A., et al. Metabolomic approach in the diadnosis of astma and COPD. Russian Biomedical Journal. 2011;4:1266–77 (In Russ.).
14. Bowerman K., Rehman S., Vaughan A., Lachner N., Budden K. Disease-associated gut microbiome and metabolome changes in patients with chronic obstructive pulmonary disease. Nat Commun. 2020;11(1):5886. DOI: 10.1038/s41467-020-19701-0
15. Zhu Т., Li S., Wang J., Liu Ch, Gao L., Zeng Yu., et al. Induced sputum metabolomic profiles and oxidative stress are associated with chronic obstructive pulmonary disease (COPD) severity: potential use for predictive, preventive, and personalized medicine. EPMA J. 2020;11(4):645–59. DOI: 10.1007/s13167-020-00227-w
16. Albornoz A., Alarcon P., Morales N., Uberti B., Henriquez C., Manosalva C., et al. Metabolomics analysis of bronchoalveolar lavage fluid samples in horses with naturally-occurring asthma and experimentally-induced airway inflammation. Res Vet Sci. 2020;133:276–82. DOI: 10.1016/j.rvsc.2020.09.033
17. Villaseñor A., Eguiluz-Gracia I., Moreira A., Wheelock C.E., Escribese M.M. Metabolomics in the Identification of Biomarkers of Asthma. Metabolites. 2021;11(6):346. DOI: 10.3390/metabo11060346
18. Lee-Sarwar K.A., Kelly R.S., Lasky-Su J., Zeiger R.S., O’Connor G.T., Sandel M.T., et al. Integrative analysis of the intestinal metabolome of childhood asthma. J Allergy Clin Immunol. 2019;144(2):442–54. DOI: 10.1016/j.jaci.2019.02.032
19. Ivashkin V., Zolnikova O., Potskherashvili N., Trukhmanov A., Kokina N., Dzhakhaya N., et al. A metabolic activity of the intestinal microflora in patients with bronchial asthma. Clinics and Practice. 2019;9:1126. DOI: 10.4081/cp.2019.1126
20. Xu S., Panettieri R., Jude J. Metabolomics in asthma: A platform for discovery. Mol Aspects Med. 2021;3:100990. DOI: 10.1016/j.mam.2021.100990
21. Wang C., Jiang S., Zhang S., Ouyang Z., Wang G., Wang F. Research Progress of Metabolomics in Asthma. Metabolites. 2021;11(9):567. DOI: 10.3390/meta-bo11090567
22. Papamichael M., Katsardis C., Sarandi E., Georgaki S., Frima E.S., Varvarigou A. et al. Application of Metabolomics in Pediatric Asthma: Prediction, Diagnosis and Personalized Treatment. Metabolites. 2021;11(4):251. DOI: 10.3390/metabo11040251
23. Hasegawa K., Stewart C.J., Celedón J.C., Mansbach J.M., Tierney C., Camargo C.A. Serum 25-hydroxyvitamin D, metabolome, and bronchiolitis severity among infants-A multicenter cohort study. Pediatr Allergy Immunol. 2018;29(4):441–5. DOI: 10.1111/pai.12880
24. Grassin-Delyle S., Roquencourt C., Moine P., Saffroy G., Carn S., Heming N. Metabolomics of exhaled breath in critically ill COVID-19 patients: A pilot study. EBioMedicine. 2021;63:103154. DOI: 10.1016/j.ebiom.2020.103154
25. Tang W.H., Wang Z., Levison B.S., Koeth R.A., Britt E.B. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368:1575–84. DOI: 10.1056/NEJMoa1109400
26. Amin A.M. Metabolomics applications in coronary artery disease personalized medicine. Adv Clin Chem. 2021;102:233–70. DOI: 10.1016/bs.acc.2020.08.003
27. Murthy V.L., Reis J.P., Pico A.R., Kitchen R., Lima J.A., Lloyd-Jones D., et al. Comprehensive Metabolic Phenotyping Refines Cardiovascular Risk in Young Adults. Circulation. 2020;142(22):2110–27. DOI: 10.1161/CIRCULATIONAHA.120.047689
28. Koeth R. A., Wang Z., Levison B., Buffa J., Org E., et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 2013;19:576–85. DOI: 10.1038/nm.3145
29. Wang Z., Tang W., Buffa J., Fu X., Britt E., et al. Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur Heart J. 2014:35;904–10. DOI: 10.1093/eurheartj/ehu002
30. Nayor M., Brown K.J., Vasan R.S. The Molecular Basis of Predicting Atherosclerotic Cardiovascular Disease Risk. Circ Res. 2021;128(2):287–303. DOI: 10.1161/CIRCRESAHA.120.315890
31. Warrier M., Shih D., Burrows A., Ferguson D., Gromovsky A., Brown A., et al. The TMAO-generating enzyme flavin monooxygenase 3 is a central regulator of cholesterol balance. Cell Rep. 2015;10:326–38. DOI: 10.1016/j.celrep.2014.12.036
32. Chen X., Liu L., Palacios G. Plasma metabolomics reveals biomarkers of the atherosclerosis. Journal of Separation Science. 2010;33:2776–83. DOI: 10.1002/jssc.201000395
33. Deidda M., Piras C., Dessalvi C. Metabolomic approach to functional and metabolic myocardial changes in heart failure. Journal of Translational Medicine. 2015;13:297. DOI: 10.1186/s12967-015-0661-3
34. Zordoky B.N., Sung M.M., Ezekowitz J. Metabolomic Fingerprint of Heart Failure with Preserved Ejection Fraction. PLoS ONE. 2015;10(5):e0124844. DOI: 10.1371/journal.pone. 0124844
35. Wishart D.S. Is cancer a genetic disease or a metabolic disease? EBioMedicine. 2015;2(6):478–9. DOI: 10.1016/j.ebiom.2015.05.022
36. Qu W., Oya S., Lieberman B., Ploessl K., Wang L., et al. Preparation and characterization of L-[5-11C]-glutamine for metabolic imaging of tumors. J Nucl Med. 2012;53(1):98–105. DOI: 10.2967/jnumed.111.093831
37. Losman J.A., Looper R., Koivunen P. (R)-2-hydroxy-glutarate is sufficient to promote leukemogenesis and its effects are reversible. Science. 2013;339(6127):1621–5. DOI: 10.1126/science.1231677
38. Zhu L., Ploessl K., Zhou R., Mankoff D., Kung H. Metabolic Imaging of Glutamine in Cancer. J Nucl Med. 2017;58(4):533–7. DOI: 10.2967/jnumed.116.182345
39. Lisitsa A.V., Ponomarenko E.A., Lokhov P.G., Archakov A.I. Postgenomic Medicine: Alternative to Biomarkers. Annals of the Russian Academy of Medical Sciences. 2016;71(3):255–60 (In Russ.). DOI: 10.15690/vramn64
40. Davis V.W., Schiller D.E., Eurich D. Urinary metabolomic signature of esophageal cancer and Barrett’s esophagus. World J Surg Onc. 2021;10:271. DOI: 10.1186/1477-7819-10-271
41. Bhatt A.P., Redinbo M.R., Bultman S.J. The role of the microbiome in cancer development and therapy. CA Cancer J Clin. 2017;67(4):326–44. DOI: 10.3322/caac.21398
42. Bar N., Korem T. , Weissbrod O., Zeevi D, Rothschildm D., et al. A reference map of potential determinants for the human serum metabolome. Nature. 2020;588(7836):135–40. DOI: 10.1038/s41586-020-2896-2
43. De Angelis M., Garruti G., Minervini F., Bonfrate L., Portincasa P., Gobbetti M. The Food-gut Human Axis: The Effects of Diet on Gut Microbiota and Metabolome. Curr Med Chem. 2019;26(19):3567–83. DOI: 10.2174/0929867324666170428103848
44. Chen Z.Z., Gerszten R.E. Metabolomics and Proteomics in Type 2 Diabetes. Circ Res. 2020;126(11):1613–27. DOI: 10.1161/CIRCRESAHA.120.315898
45. Willkommen D., Lucio M., Moritz F., Forcisi S., Kanawati B., Smirnov K., et al. Metabolomic investigations in cerebrospinal fl uid of Parkinson’s disease. PLoS One. 2018;13(12):e0208752. DOI: 10.1371/journal.pone.0208752
46. He R., Yan X., Guo J., Xu Q., Tang B., Sun Q. Recent Advances in Biomarkers for Parkinson’s Disease. Front Aging. Neurosci. 2018;10:305. DOI: 10.3389/fnagi.2018.00305
47. Orešič M., Tang J., Seppänen-Laakso T., Mattila I., Saarni S.E., Saarni S.I., et al. Metabolome in schizophrenia and other psychotic disorders: a general population-based study. Genome Med. 2011;3(3):19. DOI: 10.1186/gm233
48. Tripp B.A., Dillon S.T., Yuan M., Asara J.M., Vasunilashorn S.M., Fong T.G., et al. Targeted metabolomics analysis of postoperative delirium. Sci Rep. 2021;11(1):1521. DOI: 10.1038/s41598-020-80412-z
49. Liu L., Zhao J., Chen Y., Feng R. Metabolomics strategy assisted by transcriptomics analysis to identify biomarkers associated with schizophrenia. Anal Chim Acta. 2020;1140:18–29. DOI: 10.1016/j.aca.2020.09.054
50. Wu L., Han Y., Zheng Z., Peng G., Liu P., Yue S., et al. Altered Gut Microbial Metabolites in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: Signals in Host-Microbe Interplay. Nutrients. 2021;13(1):228. DOI: 10.3390/nu13010228.
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For citations:
Zolnikova O.Yu., Reshetova M.S., Ivanova M.N., Ivashkin V.T. Metabolomic profiles as a new understanding of disease processes. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2022;32(1):46-52. https://doi.org/10.22416/1382-4376-2022-32-1-46-52
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