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. 2023 Mar 20;8:132. doi: 10.1038/s41392-023-01399-3

Table 1.

Small-molecule metabolites and relevant metabolic alterations associated with human diseases in recent clinical studies

Disease type Reference No. of patient Biological matrix Research aim Analytical platform Potential biomarkers Key pathways
Hepatolithiasis Cong Wang et al.475 30 Serum Phenotype UPLC-MS

18-β-Glycyrrhetinic acid,

PC (4:0/16:2)

 Taurine and hypotaurine metabolism, bile secretion
Traumatic brain injury Elani A. Bykowski et al.478 8 Urine Phenotype NMR

Homovanillate,

L-methionine, thymine

 Purine metabolism
COVID-19 Laura Ansone et al.477 32 Serum Phenotype LC-MS L-phenylalanine, tyrosine Tryptophan and arginine metabolism
Asthma Ying Liu et al.473 119 Sputum Phenotype UPLC-MS Adenosine 5′-monophosphate, allantoin, nicotinamide Histidine metabolism, nicotinate, nicotinamide metabolism
Diabetic kidney disease Shijia Liu et al.526 1513 Serum diagnosis GC-MS Glycerol-3-galactoside Galactose metabolism, glycerolipid metabolism
Nonalcoholic fatty liver disease Xuemei Wang et al.519 149 Serum diagnosis UPLC-MS Theophylline, 2-hydroxyphenylacetic acid, lysophosphatidylcholine (24:1(15Z)) Caffeine metabolism, choline metabolism and sphingolipid metabolism
Tuberculosis Xin Hu et al.520 64 Plasma diagnosis UPLC-MS

9-OxoODE,

DL-Norvaline,

Ethyl 3-hydroxybutyrate

 Lipid synthesis and biosynthesis of glutathione
Breast cancer Rui An et al.521 216 Plasma diagnosis UPLC-MS Sphingomyelins, glutamate, cysteine Alanine, aspartate and glutamate pathways, glutamine metabolic pathway
Oral squamous cell carcinoma Xibo Li et al.524 72 Plasma diagnosis UPLC-MS Decanoylcarnitine, cysteine, cholic acid Cholic and amino acid metabolism
Salivary gland tumors Mengmeng Wu et al.544 30 Serum Classification UPLC-MS Serine, lactic acid Metabolism of fats and fatty acids, anaerobic glycolysis
Endometrial diseases Xingxu Yan et al.552 326 Serum Classification UPLC-MS

6-ketoPGF1α,

PA(37:4),

LysoPC(20:1)

 Glycerophospholipid metabolism
Papillary thyroid cancer Shuang Yu et al.550 148 Plasma Classification UPLC-MS Capryloylglycine, valeric acid, triethanolamine, imidazoleacetic acid, etc.
COVID-19 AlbertoValdés et al.551 145 Plasma Classification HPLC-MS

3-Hydroxibutirate, linoleic acid,

LPC (14:0 and 18:2),

LPE (22:6), kynurenic acid

 Metabolism of carnitines, ketone bodies, fatty acids, and lysophosphatidylcholines
Bladder Cancer, Prostate Cancer, Renal Cell Carcinoma Sujin Lee et al.554

24,

29,

12

 Urine Classification NMR

4-Hydroxybenzoate,

N-methylhydantoin,creatinine, glutamine, acetate
Coronary atherosclerotic heart disease Yuxuan Fan et al.547 60 Serum Classification UPLC-MS

5-Cholesten-3β,

N-Acetyl-lysine, tyramine, biliverdin, urocanate, etc.

 Energy, lipid m and amino acid metabolism
COVID-19 IvaylaRoberts et al.577 120 Serum Prognosis UPLC-MS Deoxycytidine, ureidopropionate, kynurenine, multiple short chain acylcarnitines Pyrimidine, kynurenine, and energy metabolism
Type 2 diabetes mellitus Julia Brunmair et al.580 8 Sweat, tear fuid Prognosis HPLC-MS Nicotinic acid, taurine
Acute ischemic stroke Chaofu Ke et al.579 143 Blood Prognosis HPLC-MS

LysoPC(18:1),

Lys Val Phe Lys,

LysoPC(18:2),

PS(O-18:0/0:0)
COVID-19 Victòria Ceperuelo-Mallafre et al.575 273 Serum Prognosis GC-MS Pyruvate, lactate, succinate, a-ketoglutarate Krebs cycle
COVID-19 Lucas Barbosa Oliveira et al.537 242 Plasma Prognosis HESI-Q-Orbitrap Cholesteryl ester CE (18:3) Glycerophospholipid and porphyrin metabolism
Neuroblastoma Sebastiano Barco et al.578 172 Plasma Prognosis HRMS 3-O-methyldopa
Colorectal Cancer Xinyi Shen et al.581 197 Tissues Prognosis UPLC-MS, HPLC-MS Asparagine, serine Asparagine synthesis pathway, serine metabolism
Allergic rhinitis Rui-Li Yu et al.619 43 Serum Treatment GC-MS Hypotaurine, taurine, L-alanine, Taurine and hypotaurine metabolism, and alanine metabolism
Epileptic spasms Jingya Yan et al.621 34 Cerebrospinal fluid Treatment LC-MS

Kynurenic acid,

3-hydroxykynurenine, xanthurenic acid, anthranilic acid, quinolinic acid, picolinic acid, etc.

 Kynurenine pathway
Rheumatoid arthritis Matthew R. Medcalf et al.624 20 Plasma Treatment GC-MS

N-methylisoleucine,

2,3-dihydroxybutanoic acid
Schizophrenia Xiaoni Guan et al.622 25 Plasma Treatment UPLC-MS Methyl n-formylanthranilate Kynurenine pathway of tryptophan metabolism
Psoriasis vulgaris Dan Dai et al.623 88 Blood Treatment UPLC-MS

SM (d16: 0/17:1),

SM (d19:1/20:0),

Cer (d18:1/18:0),

PC (18:0/22:4),

PC (20:0/22:4)

 Lipid metabolism dysfunction
Polypoidal choroidal vasculopathy Yinchen Shen et al.620 93 Serum Treatment UPLC-MS Dacylglycerophosphocholines, lysophosphatidylcholine, fatty acids, phosphocholine Lysophosphatidylcholine and diacylglycerophosphocholine metabolism
Breast cancer Ehsan Irajizad et al.617 88 Plasma Treatment UPLC-MS Polyamines
Bladder Cancer Juntao Zhuang et al.618 18 Serum Treatment NMR, UPLC-MS Glutamine, glutamate, hypoxanthine Amino acid pathways
Colorectal cancer Yu Yuan et al.676 30 Serum Function UPLC-MS Glycodeoxycholic acid Poly (ADP-ribose) polymerase-1
Breast cancer Yi Xiao et al.22 330 Tissues Function LC-MS Sphingosine-1-phosphate Ceramide pathway
Acute traumatic brain injury Ilias Thomas et al.673 716 Serum Function UPLC-MS Lysophosphatidylcholines, ether phosphatidylcholines, sphingomyelins
Type 2 diabetes Maria Giovanna Scarale et al.675 279 Serum Function LC-MS Hexanoylcarnitine, kynurenine, tryptophan
Kawasaki disease Qiongjun Zhu et al.674 79 Blood Function LC-MS Palmitic acid Generation of reactive oxygen species
Aortic aneurysm Hongtu Cui et al.164 1705 Plasma Function UPLC-MS Succinate p38a/CREB/OGDH axis

UPLC-MS ultra performance liquid chromatography-tandem mass spectrometry, NMR nuclear magnetic resonance, LC-MS liquid chromatography-tandem mass spectrometry, GC-MS gas chromatography coupled to mass spectrometry