Clinical metabolomics: Useful insights, perspectives, and challenges.

Notice

This is an unedited manuscript accepted for publication and provided as an Article in Press for early access at the author’s request. The article will undergo copyediting, typesetting, and galley proof review before final publication. Please be aware that errors may be identified during production that could affect the content. All legal disclaimers of the journal apply.

Year : 2026 | Volume : 3 | 01 | Page :
    By

    Atul Khajuria 1,

  • Mahesh Gaba 2 *,

  1. Dean, Department of Allied & Health Care Sciences, Rayat Bahra Professional University, Hoshiarpur, Chandigarh Rd, VPO, Bohan, Hoshiarpur, Punjab, India
  2. Faculty, department of Medical Laboratory Science, PCTE Group of Institutes, Jhande [Ludhiana], punjab, India

Abstract

Metabolomics provides a comprehensive snapshot of smallmolecule intermediates and end products of cellular processes and thereby links genotype, environment, and phenotype in human disease . Over the last decade, advances in liquid chromatography–mass spectrometry (LC–MS) and nuclear magnetic resonance (NMR) spectroscopy have enabled high-throughput profiling of thousands of metabolites from microliter volumes of clinical samples . Clinical metabolomics is now emerging as a tool for disease diagnosis, risk prediction, therapeutic monitoring, and mechanistic discovery across cardiometabolic, neurologic, renal, and inflammatory disorders. In diabetic kidney disease, metabolomics has identified early alterations in aminoacid, lipid, and energy pathways and candidate biomarkers that precede albuminuria or decline in estimated glomerular filtration rate (eGFR) . In Alzheimer’s disease, targeted and untargeted metabolomics in plasma, cerebrospinal fluid (CSF), and brain tissue have
highlighted disturbances in branchedchain amino acids, nicotinamide adenine dinucleotide (NAD⁺) homeostasis, polyamine and Larginine metabolism, and tryptophan–kynurenine pathways, some of which correlate with amyloid and tau biomarkers and cognitive decline . Despite impressive discovery output, translation into clinical tests remains limited, impeded by issues of analytical standardization, inter- laboratory reproducibility, causal inference, and regulatory and implementation barriers. This
review summarizes principles of clinical metabolomics, highlights key disease-related metabolites in diabetic kidney disease and Alzheimer’s disease, and discusses the main technical, statistical, and translational challenges for bringing metabolomic biomarkers and signatures into routine clinical practice .

Keywords: KEYWORDS -Clinical metabolomics; Disease biomarkers; Diabetic kidney disease; Diabetic nephropathy; Alzheimer’s disease; Mass spectrometry; Metabolic profiling; Translational medicine.

How to cite this article:
Atul Khajuria 1, Mahesh Gaba 2 *. Clinical metabolomics: Useful insights, perspectives, and challenges.. Emerging Trends in Metabolites. 2026; 03(01):-.
How to cite this URL:
Atul Khajuria 1, Mahesh Gaba 2 *. Clinical metabolomics: Useful insights, perspectives, and challenges.. Emerging Trends in Metabolites. 2026; 03(01):-. Available from: https://journals.stmjournals.com/etm/article=2026/view=239640


References

1. Rinschen MM, Ivanisevic J, Giera M, Siuzdak G. Clinical metabolomics: useful insights, perspectives and challenges. Clin Chem Lab Med. 2024;62(7):e1–e15.​
2. Newgard CB. Metabolomics and metabolic diseases: where do we stand? Cell Metab. 2017;25(1):4356.​
3. Lindon JC, Nicholson JK. Spectroscopic and statistical techniques for information recovery in metabonomics and metabolomics. Annu Rev Anal Chem. 2008; 1:4569.​
4. Patti GJ, Yanes O, Siuzdak G. Innovation: metabolomics: the apogee of the omics trilogy. Nat Rev Mol Cell Biol. 2012;13(4):2639.​
5. Holčapek M, Liebisch G, Ekroos K. Lipidomic analysis. Anal Chem. 2018;90(7):424957.​
6. Xiao JF, Zhou B, Ressom HW. Metabolomics and its application in the development of biomarkers for diabetes and cardiovascular diseases. Crit Rev Clin Lab Sci. 2013;50(6):35971.​
7. Xiao JF, Zhou B, Ressom HW. Recent advances in LC–MSbased metabolomics for clinical applications. Mass Spectrom Rev. 2022;41(1):72109.​
8. Dunn WB, Ellis DI. Metabolomics: current analytical platforms and methodologies. TrAC Trends Anal Chem. 2005;24(4):28594.​
9. Johnson CH, Ivanisevic J, Siuzdak G. Metabolomics: beyond biomarkers and towards mechanisms. Nat Rev Mol Cell Biol. 2016;17(7):4519.​
10. Nicholson JK, Lindon JC, Holmes E. ‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR data. Xenobiotica. 1999;29(11):11819.​
11. Roberts LD, Gerszten RE. Toward new biomarkers of cardiometabolic diseases. Cell Metab. 2013;18(1):4350.​
12. Würtz P, Havulinna AS, Soininen P, et al. Metabolite profiling and cardiovascular event risk: a prospective study of 3 populationbased cohorts. Circulation. 2015;131(9):77485.​
13. Nowak C, Ärnlöv J. A metabolomics view on the pathophysiology of cardiovascular disease. Eur J Prev Cardiol. 2018;25(2 suppl):3742.​
14. Würtz P, Raiko JR, Magnussen CG, et al. Highthroughput quantification of circulating metabolites improves prediction of subclinical atherosclerosis. Eur Heart J. 2012;33(18):230716.​
15. MookKanamori DO, Selim MME, Takiddin AH, et al. 1HNMRbased urine metabolomics reveals systemic metabolic alterations in obesity. BMC Syst Biol. 2014;8 Suppl 1:S2.​
16. Tiwari S, et al. Comprehensive metabolomics profiling reveals novel biomarkers and metabolic signatures in Alzheimer’s disease. Brain Commun. 2025;7(6):fcaf410.​
17. Jové M, et al. Integrative metabolomics science in Alzheimer’s disease. Alzheimers Dement. 2023;19(6):204463.​
18. Orešič M, Hyötyläinen T, Herukka SK, et al. Metabolomics of Alzheimer’s disease. Front Neurol. 2018;8:719.​
19. GonzálezDomínguez R, GarcíaBarrera T, GómezAriza JL. Metabolomic study of lipids in serum for biomarker discovery in Alzheimer’s disease using direct infusion mass spectrometry. J Pharm Biomed Anal. 2014;98:3216.​
20. Trushina E, Mielke MM. Recent advances in the application of metabolomics to Alzheimer’s disease. Biochim Biophys Acta. 2014;1842(8):12329.​
21. Graham SF, Chevallier OP, Elliott CT, et al. Untargeted metabolomic analysis of human plasma indicates differentially affected polyamine and Larginine metabolism in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis. 2015;46(2):31327.​
22. Jové M, PorteroOtin M, Naudí A, et al. Plasma lipidomics discloses metabolic signatures of sporadic Alzheimer’s disease and its preclinical stages. Alzheimers Dement. 2015;11(4):43744.​
23. Varma VR, Oommen AM, Varma S, et al. Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: a targeted metabolomics study. PLoS Med. 2018;15(1):e1002482.​
24. Toledo JB, Arnold M, Kastenmüller G, et al. Metabolic network failures in Alzheimer’s disease: a biochemical road map. Alzheimers Dement. 2017;13(9):96584.​
25. Mapstone M, Cheema AK, Fiandaca MS, et al. Plasma phospholipids identify antecedent memory impairment in older adults. Nat Med. 2014;20(4):4158.​
26. Li X, Liu W, Jiang H, et al. Metabolomics in diabetic nephropathy: unveiling novel biomarkers and pathways. Mol Med Rep. 2024;29(2):13280.
27. Li X, Liu W, Jiang H, et al. Metabolomics in diabetic nephropathy: unveiling novel biomarkers for early diagnosis and progression. Mol Med Rep. 2024;29(2):13280.​
28. Kikuchi M, Muraoka H, Ohashi N, et al. Potential progression biomarkers of diabetic kidney disease determined using comprehensive machinelearning analysis of nontargeted metabolomics. Sci Rep. 2022;12:16523.​
29. Niewczas MA, Mathew AV, Croall S, et al. Circulating modified metabolites and their association with kidney function decline in diabetic kidney disease. Nephrol Dial Transplant. 2022;37(12):222434.​
30. Bhensdadia NM, Hunt KJ, LopesVirella MF, et al. Urine haptoglobin levels predict early renal functional decline in patients with type 2 diabetes. Kidney Int. 2013;83(6):113643.​
31. Pena MJ, Lambers Heerspink HJ, Hellemons ME, et al. Urine and plasma metabolites predict the development of diabetic nephropathy in individuals with type 2 diabetes. Diabetologia. 2014;57(6):116473.​
32. PapadopoulouMarketou N, Chrousos GP, KanakaGantenbein C. Diabetic nephropathy in type 1 diabetes: a review of early natural history, pathogenesis and diagnosis. Diabetes Metab Res Rev. 2017;33(2):e2841.​
33. Sharma K, Karl B, Mathew AV, et al. Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease. J Am Soc Nephrol. 2013;24(11):190112.​
34. Liu JJ, Liu S, Gurung RL, et al. Urinary metabolites associated with the rate of kidney function decline in patients with type 2 diabetes. Clin J Am Soc Nephrol. 2020;15(7):94151.​
35. Curovic VR, Suvitaival T, Mathew AV, et al. Plasma metabolomic profiling of advanced diabetic kidney disease. Kidney Int Rep. 2020;5(10):193042.​
36. Lucarelli G, et al. Challenges in metabolomicsbased tests and biomarkers revealed by the metabolomic platform in clinical practice. Metabolites. 2022;12(5):430.​
37. Dettmer K, Aronov PA, Hammock BD. Mass spectrometrybased metabolomics. Mass Spectrom Rev. 2007;26(1):5178.​
38. Alonso A, Marsal S, Julià A. Analytical methods in untargeted metabolomics: state of the art in 2015. Front Bioeng Biotechnol. 2015;3:23.​
39. Beger RD, Dunn W, Schmidt MA, et al. Metabolomics enables precision medicine: “A White Paper, Community Perspective”. Metabolomics. 2016;12(10):149.​
40. Armitage EG, Southam AD. Monitoring cancer prognosis, diagnosis and treatment efficacy using metabolomics and lipidomics. Metabolomics. 2016;12(9):146.​
41. Pinu FR, Beale DJ, Paten AM, et al. Systems biology and multiomics integration: viewpoints from the metabolomics research community. Metabolites. 2019;9(4):76.​
42. Wishart DS. Emerging applications of metabolomics in drug discovery and precision medicine. Nat Rev Drug Discov. 2016;15(7):47384.​
43. Bujak R, StruckLewicka W, Markuszewski MJ, Kaliszan R. Metabolomics for laboratory diagnostics. J Pharm Biomed Anal. 2015;113:10820.​
44. Bujak R, et al. What clinical metabolomics will bring to the medicine of tomorrow. Front Anal Sci. 2023;3:1142606.​
45. Nicholson JK, Holmes E, Elliott P. The metabolomewide association study: a new look at human disease risk factors. J Proteome Res. 2008;7(9):36378


Ahead of Print Subscription Review Article
Volume 03
01
Received 21/02/2026
Accepted 14/03/2026
Published 25/03/2026
Publication Time 32 Days


Login


My IP

PlumX Metrics