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© 2025 The Korean Society of Emergency Medicine
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/).
Conflicts of interest
The author has no conflicts of interest to declare.
Funding
The author received no financial support for this study.
Data availability
Data sharing is not applicable as no new data were created or analyzed in this study.
| Study | Platform | Subject | Metabolite identified |
|---|---|---|---|
| Lin et al. [22] (2009) | 1H NMR | CLP-induced sepsis survivors | ↑ Alanine, formate, lactate, acetoacetate, hydroxybutyrate, and acetate |
| CLP-induced sepsis nonsurvivors | |||
| Sham controls | |||
| Liu et al. [21] (2010) | LC-MS/MS | CLP-induced sepsis | (1) Sepsis and burns single pathology groups: |
| CLP-induced sepsis and burns | ↓ Uric acid and bile acid | ||
| Burns | (2) Sepsis and dual pathology groups: | ||
| Sham of CLP-induced sepsis and burns | ↑ Uracil and nitrotyrosine | ||
| (3) Exclusively in dual pathology group: | |||
| ↑ Hypoxanthine; indoxyl sulfate tryptophan; ↑ glucuronic acid and gluconic acid and proline ↑ | |||
| Izquierdo-Garcia et al. [23] (2011) | 1H NMR | CLP-induced sepsis | ↑ Alanine, formate, acetoacetate, creatine and phosphoethanolamine and myoinositol |
| Sham surgical controls | |||
| Laiakis et al. [24] (2012) | LC-MS/MS | LPS endotoxin model | (1) LPS endotoxin group: |
| Radiation with 3 Gy of γ rays | ↑ Cytosine, adenosine and O-propanolylcarnitine | ||
| Radiation with 8 Gy of γ rays | (2) LPS endotoxin and 15 Gy radiation group: | ||
| Radiation with 15 Gy of γ rays | ↑ Isethionic acid, 2-hydroxyethane-1-sulfonic acid | ||
| Controls | |||
| Li et al. [25] (2012) | LC-MS/MS | CLP-induced sepsis | Sepsis vs. noninfected sham controls: |
| Sham surgical controls | ↑ Palmitoyl-L-carnitine, creatinine, phenylalanine, isonicotinic acid; choline 5-azacytidine and ↓ 1-O-Hexadecyl-2-lyso-glycero-3-phosphorylcholine, alanine, 4-amino-5-hydroxymethyl-2-methylpyrimidine, asymmetric dimethylarginine | ||
| Li et al. [26] (2013) | 1H NMR | CLP-induced sepsis model | Sepsis vs. noninfected surgical sham: |
| CLP-induced sepsis model (+herb A) | ↑ Isobutyrate, 3-hydroxybutyrate, alanine, acetate, lactate and glucose; ↑ TAGs and FAs, ↓ proline, taurine, valine, isoleucine, arginine, lysine and ↑ threonine; ↓ choline and trimethylamine N-oxide | ||
| CLP-induced sepsis model (+herb B) | |||
| Sham surgical control | |||
| Steelman et al. [17] (2014) | LC-MS/MS | Cohort 1: | Preinduction vs. postinduction of acute laminitis: |
| Preinduction of acute laminitis | ↑ Acylcarnitine and amino acids including alanine, kynurenine, taurine and aromatic amino acids and ↓ 3-hydroxybutyrate, citrulline, cysteine, phosphatidylcholine | ||
| Postinduction of acute laminitis | (1) Combined good and poor outcome groups vs. healthy control: ↓ Citrulline | ||
| Cohort 2: | (2) Citrulline as a predictive marker of the development of acute laminitis or nonsurvival | ||
| Poor outcome | (3) Poor outcome and good outcome vs. healthy control: | ||
| Good outcome | ↑ Alanine, valine, glycine, and ↓ serine in the good and poor outcome groups compared to healthy controls. | ||
| Healthy controls | (4) Poor outcome and good outcome vs. healthy controls: | ||
| Glycine differed significantly between the two outcome | |||
| Langley et al. [27] (2014) | LC-MS/MS | Inoculation of primates with Escherichia coli | Sepsis nonsurvivors vs. survivors and differentiation of sepsis vs. healthy control: |
| Sepsis nonsurvivors | ↓ Acyl-GPCs, and↑ kynurenine, bile acids, carnitine, TCA cycle | ||
| Sepsis survivors | |||
| Healthy controls |
| Study | Platform | Subject | Metabolite identified |
|---|---|---|---|
| Mao et al. [32] (2009) | 1H NMR | Severe trauma and SIRS | MODS vs. SIRS and both trauma vs. healthy controls |
| Severe trauma and MODS | MODS: ↑ Free FAs, glycerol, creatinine, and lactate | ||
| Healthy controls | SIRS: ↑ Amino acids (predominantly BCAAs) and glucose | ||
| Cohen et al. [33] (2010) | 1H NMR | Severe trauma survivors | Survivor vs. nonsurvivors and both trauma vs. healthy control: |
| Severe trauma and nonsurvivors | ↑ Glucose, glutamate, ketone bodies, lactate, TAGs, mono-unsaturated FAs and glycerophospholipids. | ||
| Healthy controls | |||
| Park et al. [34] (2011) | 1H NMR | Acute lung injury treatment | Acute lung injury treatment vs. acute lung injury placebo: |
| Acute lung injury placebo | ↑ Lysyl moiety of albumin; alanine, LDL, VLDL, valine, cholesterol. | ||
| Healthy controls | |||
| Stringer et al. [37] (2011) | 1H NMR | Sepsis-related ALI | Sepsis-related ALI vs. healthy controls: |
| Healthy controls | ↑ Adenosine, glutathione and phosphatidylserine; ↓ sphingomyelin. | ||
| Bruegel et al. [38] (2012) | LC-MS/MS | Sepsis | LPS-activated whole blood vs. healthy controls: |
| Healthy controls | ↓ AA, PGE2, 11-HETE; TXB2. | ||
| Langley et al. [10] (2013) | LC-MS/MS | Sepsis nonsurvivors | Sepsis nonsurvivors vs. survivors: |
| Sepsis survivors | ↑ 17 Amino acid catabolites, 16 carnitine esters, 11 nucleic acid catabolites, citrate, dihydroxyacetone, malate, pyruvate, 4 free FAs; in addition to ↓ 7 GPCs and GPE, ↑ lactate, and acylcarnitines-carnitines. | ||
| Noninfected SIRS | Sepsis survivors vs. noninfected SIRS: | ||
| ↓ Citrate and malate, glycerol, glycerol 3-phosphate, phosphate, 21 amino acids and their catabolites, 12 GPCs and GPE esters, and 6 carnitine esters. | |||
| Blaise et al. [46] (2013) | 1H NMR | Trauma + sepsis | Trauma + sepsis vs. trauma – sepsis: |
| Trauma – sepsis | ↑ Aspartate, citrate, valine, hydroxybutyrate, and allantoin. | ||
| Seymour et al. [47] (2013) | LC-MS/MS | Sepsis nonsurvivors | Sepsis nonsurvivors vs. survivors: |
| Sepsis survivors | ↑ Taurochenolate sulfate and glycochenolate sulfate; ↑ cortisol, cortisone, and sulfated hormones allantoin, N1-methyladenosine, N methyladenosine, N2, N2-dimethylguanosine, N6-carbamoylthreonyladenosine, and pseudouridine | ||
| Su et al. [49] (2014) | LC-MS/MS | Severe sepsis | Sepsis vs. noninfected SIRS: |
| Uncomplicated sepsis | ↓ Lactitol dehydrate and S-phenyl-d-cysteine and ↑ in S-(3-methylbutanoyl)-dihydrolipoamide-E and N-non-anoyl glycine | ||
| Noninfected SIRS | Severe sepsis vs. uncomplicated sepsis: | ||
| Healthy controls | ↓ Glyceryl-phosphoryl-ethanolamine, Ne, Ne-dimethyl-lysine, phenylacetamide and d cysteine | ||
| Death within 24 hr: | |||
| ↓ S-(3-methylbutanoyl)-dihydrolipoamide-E, phosphatidylglycerol, glycerophosphocholine GPC, and S-succinyl glutathione | |||
| Kamisoglu et al. [30] (2015) | LC-MS/MS | Sepsis nonsurvivors | Sepsis and healthy control vs. LPS-induced endotoxemia vs. noninfected SIRS: |
| Sepsis survivors | ↑ 2-Hydroxybutyrate, mannose, bilirubin, and lipids | ||
| LPS-induced endotoxemia in healthy controls | Sepsis survivors vs nonsurvivors: | ||
| Noninfected SIRS | ↑ Acylcarnitines-carnitines were the most discriminatory metabolites | ||
| Mickiewicz et al. [51] (2014) | 1H NMR | Septic shock | Discriminatory metabolite between septic shock, SIRS, and healthy controls: |
| SIRS | 2 Hydroxybutyrate, lactate, histidine, phenylalaninephenylalanine, and arginine | ||
| Healthy controls | |||
| Mickiewicz et al. [52] (2015) | 1H NMR | Septic shock | Discriminatory metabolite between sepsis survivors and nonsurvivors: |
| ICU controls | 20 Metabolites differentiated the profiles of survivors and nonsurvivors | ||
| Garcia-Simon et al. [59] (2015) | 1H NMR | Septic shock | Discriminatory metabolite between sepsis survivors and nonsurvivors: |
| Arginine, methionine, glutamine, phenylalanine, glucose, ethanol, and hippurate showing differences between nonsurvivors and survivors | |||
| Liu et al. [53] (2016) | LC-MS/MS | Septic shock | Discriminatory metabolite: |
| 43 Significant metabolites varied in their levels when compared between survivors with nonsurvivors | |||
| 6 Primary discriminators: valine, leucine, isoleucine, citrulline, carnitine 2:0, and betanin | |||
| Ferrario et al. [54] (2016) | LC-MS/MS | Septic shock | Upregulated in nonsurvivors: |
| Polyamines, glucogenic amino acids, and kynurenine | |||
| Downregulated in nonsurvivors: | |||
| Phosphatidylcholines and lysophosphatidylcholines | |||
| Neugebauer et al. [45] (2016) | LC-MS/MS | SIRS | Discriminatory metabolite: |
| Sepsis | Acylcarnitines, glycerophospholipids and sphingolipids were altered in sepsis compared to SIRS | ||
| Cambiaghi et al. [62] (2018) | LC-MS/MS | Septic shock | Discriminatory metabolite: |
| Alteration in the lipidome of nonsurvivors was found | |||
| PC aa C42:6, PC aa C40:6, and lyso-PC species | |||
| Dalli et al. [55] (2017) | LC-MS/MS | Septic shock | Discriminatory metabolite: |
| Elevation in the levels prostaglandin F2α, leukotriene B4, resolvin E1 resolvin D5, and 17R-protectin D1 were found in nonsurvivors | |||
| Chung et al. [56] (2019) | UHPLC-MS | Septic shock | Discriminatory metabolite: |
| A significantly higher level of plasma acetylcarnitine was found in sepsis nonsurvivors when compared with survivors | |||
| Liu et al. [58] (2019) | 1H NMR | Septic shock | Discriminatory metabolite: |
| The concentrations of alanine, glutamate, glutamine, methionine, aromatic amino acids, ketone bodies, 3-hydroxybutyrate, and acetate were increased in the nonsurvivors as compared to the survivors | |||
| N-acetyl glycoprotein level was found decreased in nonsurvivors | |||
| Jaurila et al. [40] (2020) | 1H NMR | Sepsis | Discriminatory metabolite: |
| Healthy controls | Significantly higher serum lactate and citrate concentrations in nonsurvivors compared with survivors | ||
| Liang et al. [39] (2016) | LC-MS/MS | Septic shock | Discriminatory metabolite: |
| Healthy controls | Sphingosine, 5 methylcytidine, 3 dehydrocarnitine, 4 acetamido-2-aminobutanoic acid and phenyllactic acid in the septic shock subjects were significantly different from the controls | ||
| Feng et al. [48] (2022) | LC-MS/MS | Multiple trauma (non-SIRS) | Discriminatory metabolite: |
| Sepsis | 9 Potential biomarkers, namely, acrylic acid, 5-amino-3-oxohexanoate, 3b-hydroxy-5-cholenoic acid, cytidine, succinic acid semialdehyde, PE [P-18:1(9Z)/16:1(9Z)], sphinganine, uracil, and uridine were identified | ||
| Mecatti et al. [36] (2018) | LC-MS/MS | Septic shock | Discriminatory metabolite: |
| Healthy controls | FAs and phospholipids detected in plasma and erythrocytes could signal sepsis vs. nonsepsis | ||
| Lyso-PCs and SMs were downregulated, whereas the saturated and unsaturated PCs were upregulated in the plasma and erythrocytes of septic patients | |||
| Pandey et al. [41] (2021) | 1H NMR | Septic shock | Discriminatory metabolite: |
| Healthy controls | The potential biomarkerspotential biomarkers for septic shock are lactate, 3 hydroxybutyrate, 3 hydroxyisovalerate, proline, 1,2 propanediol, creatine, glycine, phenylalanine, and myoinositol, bile, NAG, and VLDL, which were significantly upregulated in septic shock patients, whereas citrate, carnitine, HDL, LDL, and lipoprotein with phosphocholine head group were downregulated in septic shock patients | ||
| Septic shock with comorbid conditions (diabetes and hypertension) | |||
| Septic shock with primary diagnosis (respiratory illness and encephalopathy) | |||
| Pandey et al. [57] (2023) | 1HNMR | Septic shock pretreatment | Discriminatory metabolite: |
| Septic shock posttreatment | The study showed time-dependent metabolite alteration in ketone bodies, amino acids, choline, and NAG in patients undergoing treatment. | ||
| Cambiaghi et al. [65] (2017) | LC- MS/MS | Treatment response in septic shock | Discriminatory metabolite: |
| Lipidome alterations play an important role in individual patients' responses to infection | |||
| Furthermore, alanine indicates a possible alteration in the glucose-alanine cycle in the liver, providing a different picture of liver functionality from bilirubin | |||
| Kauppi et al. [50] (2016) | LC-MS/MS | Sepsis | Discriminatory metabolite: |
| Healthy controls | 6 Metabolites were identified for bacteremic sepsis | ||
| Winkler et al. [61] (2018) | LC- MS/MS | Sepsis | Discriminatory metabolite: |
| SDMA and ADMA associated with sepsis mortality | |||
| Huang et al. [60] (2019) | LC- MS/MS | Septic shock | Discriminatory metabolite: |
| Phenylalanine- and leucine-defined risk classifications provide metabolic information with prognostic value for patients with severe infection | |||
| Li et al. [44] (2023) | LC-MS/MS | Sepsis | Discriminatory metabolite: |
| Healthy controls | 3-Phenyl lactic acid, N-phenylacetylglutamine, phenylethylamine, traumatin, xanthine, methyl jasmonate, indole, l-tryptophan | ||
| Chen et al. [66] (2022) | LC-MS/MS | Sepsis | Discriminatory metabolite: |
| Healthy controls | 73 Differentially expressed metabolites that could predict sepsis were identified. | ||
| Pandey et al. [42] (2022) | 1H NMR | Septic shock survivor (male/female) | Discriminatory metabolite: |
| Septic shock nonsurvivor (male/female) | The energy-related metabolites, ketone bodies, choline, and NAG were found to be primarily responsible for differentiating survivors and nonsurvivors | ||
| The sex-based mortality stratification identified a female-specific association of the anti-inflammatory response, innate immune response, and β oxidation, and a male-specific association of the proinflammatory response to septic shock | |||
| Puskarich et al. [64] (2015) | LC- MS/MS | Carnitine treatment response in septic shock | Drug responsive metabolite: |
| Responsive towards carnitine treatment | |||
| Evans et al. [63] (2019) | LC- MS/MS | Carnitine treatment response in septic shock | Drug responsive metabolite: |
| Metabolic signature of L-carnitine-treated nonsurvivors is associated with a severity of illness (e.g., vascular inflammation) that is not routinely clinically detected | |||
| Pandey et al. [43] (2023) | 1H NMR | Treatment response in septic shock | Drug responsive metabolite: |
| 3 Hydroxybutyrate, lactate, and phenylalanine which were lower, whereas glutamate and choline higher in patients showing responsiveness |
NMR, nuclear magnetic resonance; SIRS, systemic inflammatory response syndrome; MODS, multiorgan dysfunction syndrome; FA, fatty acid; BCAA, branched-chain amino acid; TAG, triacylglyceride; LDL, low-density lipoprotein; VLDL, very low-density lipoprotein; ALI, acute liver injury; LC-MS/MS, liquid chromatography coupled mass spectrometry; LPS, lipopolysaccharides; AA, arachidonic acid; PGE2, prostaglandin E2; 11-HETE, 11-hydroxyeicosatetraenoic acid; TXB2, thromboxane B2; GPC, glycerophosphocholine; GPE, glycerophosphoethanolamine; ICU, intensive care unit; PC, phosphatidylcholine; UHPLC-MS, ultrahigh performance liquid chromatography coupled with mass spectrometry; SM, sphingomyelin; NAG, N-acetylglycoprotein; HDL, high-density lipoprotein; SDMA, symmetric dimethylarginine; ADMA, assymmetric dimethylarginine.
Adapted from Pandey [35], available under the Creative Commons License.
| Study | Platform | Subject | Metabolite identified |
|---|---|---|---|
| Lin et al. [22] (2009) | 1H NMR | CLP-induced sepsis survivors | ↑ Alanine, formate, lactate, acetoacetate, hydroxybutyrate, and acetate |
| CLP-induced sepsis nonsurvivors | |||
| Sham controls | |||
| Liu et al. [21] (2010) | LC-MS/MS | CLP-induced sepsis | (1) Sepsis and burns single pathology groups: |
| CLP-induced sepsis and burns | ↓ Uric acid and bile acid | ||
| Burns | (2) Sepsis and dual pathology groups: | ||
| Sham of CLP-induced sepsis and burns | ↑ Uracil and nitrotyrosine | ||
| (3) Exclusively in dual pathology group: | |||
| ↑ Hypoxanthine; indoxyl sulfate tryptophan; ↑ glucuronic acid and gluconic acid and proline ↑ | |||
| Izquierdo-Garcia et al. [23] (2011) | 1H NMR | CLP-induced sepsis | ↑ Alanine, formate, acetoacetate, creatine and phosphoethanolamine and myoinositol |
| Sham surgical controls | |||
| Laiakis et al. [24] (2012) | LC-MS/MS | LPS endotoxin model | (1) LPS endotoxin group: |
| Radiation with 3 Gy of γ rays | ↑ Cytosine, adenosine and O-propanolylcarnitine | ||
| Radiation with 8 Gy of γ rays | (2) LPS endotoxin and 15 Gy radiation group: | ||
| Radiation with 15 Gy of γ rays | ↑ Isethionic acid, 2-hydroxyethane-1-sulfonic acid | ||
| Controls | |||
| Li et al. [25] (2012) | LC-MS/MS | CLP-induced sepsis | Sepsis vs. noninfected sham controls: |
| Sham surgical controls | ↑ Palmitoyl-L-carnitine, creatinine, phenylalanine, isonicotinic acid; choline 5-azacytidine and ↓ 1-O-Hexadecyl-2-lyso-glycero-3-phosphorylcholine, alanine, 4-amino-5-hydroxymethyl-2-methylpyrimidine, asymmetric dimethylarginine | ||
| Li et al. [26] (2013) | 1H NMR | CLP-induced sepsis model | Sepsis vs. noninfected surgical sham: |
| CLP-induced sepsis model (+herb A) | ↑ Isobutyrate, 3-hydroxybutyrate, alanine, acetate, lactate and glucose; ↑ TAGs and FAs, ↓ proline, taurine, valine, isoleucine, arginine, lysine and ↑ threonine; ↓ choline and trimethylamine N-oxide | ||
| CLP-induced sepsis model (+herb B) | |||
| Sham surgical control | |||
| Steelman et al. [17] (2014) | LC-MS/MS | Cohort 1: | Preinduction vs. postinduction of acute laminitis: |
| Preinduction of acute laminitis | ↑ Acylcarnitine and amino acids including alanine, kynurenine, taurine and aromatic amino acids and ↓ 3-hydroxybutyrate, citrulline, cysteine, phosphatidylcholine | ||
| Postinduction of acute laminitis | (1) Combined good and poor outcome groups vs. healthy control: ↓ Citrulline | ||
| Cohort 2: | (2) Citrulline as a predictive marker of the development of acute laminitis or nonsurvival | ||
| Poor outcome | (3) Poor outcome and good outcome vs. healthy control: | ||
| Good outcome | ↑ Alanine, valine, glycine, and ↓ serine in the good and poor outcome groups compared to healthy controls. | ||
| Healthy controls | (4) Poor outcome and good outcome vs. healthy controls: | ||
| Glycine differed significantly between the two outcome | |||
| Langley et al. [27] (2014) | LC-MS/MS | Inoculation of primates with Escherichia coli | Sepsis nonsurvivors vs. survivors and differentiation of sepsis vs. healthy control: |
| Sepsis nonsurvivors | ↓ Acyl-GPCs, and↑ kynurenine, bile acids, carnitine, TCA cycle | ||
| Sepsis survivors | |||
| Healthy controls |
| Study | Platform | Subject | Metabolite identified |
|---|---|---|---|
| Mao et al. [32] (2009) | 1H NMR | Severe trauma and SIRS | MODS vs. SIRS and both trauma vs. healthy controls |
| Severe trauma and MODS | MODS: ↑ Free FAs, glycerol, creatinine, and lactate | ||
| Healthy controls | SIRS: ↑ Amino acids (predominantly BCAAs) and glucose | ||
| Cohen et al. [33] (2010) | 1H NMR | Severe trauma survivors | Survivor vs. nonsurvivors and both trauma vs. healthy control: |
| Severe trauma and nonsurvivors | ↑ Glucose, glutamate, ketone bodies, lactate, TAGs, mono-unsaturated FAs and glycerophospholipids. | ||
| Healthy controls | |||
| Park et al. [34] (2011) | 1H NMR | Acute lung injury treatment | Acute lung injury treatment vs. acute lung injury placebo: |
| Acute lung injury placebo | ↑ Lysyl moiety of albumin; alanine, LDL, VLDL, valine, cholesterol. | ||
| Healthy controls | |||
| Stringer et al. [37] (2011) | 1H NMR | Sepsis-related ALI | Sepsis-related ALI vs. healthy controls: |
| Healthy controls | ↑ Adenosine, glutathione and phosphatidylserine; ↓ sphingomyelin. | ||
| Bruegel et al. [38] (2012) | LC-MS/MS | Sepsis | LPS-activated whole blood vs. healthy controls: |
| Healthy controls | ↓ AA, PGE2, 11-HETE; TXB2. | ||
| Langley et al. [10] (2013) | LC-MS/MS | Sepsis nonsurvivors | Sepsis nonsurvivors vs. survivors: |
| Sepsis survivors | ↑ 17 Amino acid catabolites, 16 carnitine esters, 11 nucleic acid catabolites, citrate, dihydroxyacetone, malate, pyruvate, 4 free FAs; in addition to ↓ 7 GPCs and GPE, ↑ lactate, and acylcarnitines-carnitines. | ||
| Noninfected SIRS | Sepsis survivors vs. noninfected SIRS: | ||
| ↓ Citrate and malate, glycerol, glycerol 3-phosphate, phosphate, 21 amino acids and their catabolites, 12 GPCs and GPE esters, and 6 carnitine esters. | |||
| Blaise et al. [46] (2013) | 1H NMR | Trauma + sepsis | Trauma + sepsis vs. trauma – sepsis: |
| Trauma – sepsis | ↑ Aspartate, citrate, valine, hydroxybutyrate, and allantoin. | ||
| Seymour et al. [47] (2013) | LC-MS/MS | Sepsis nonsurvivors | Sepsis nonsurvivors vs. survivors: |
| Sepsis survivors | ↑ Taurochenolate sulfate and glycochenolate sulfate; ↑ cortisol, cortisone, and sulfated hormones allantoin, N1-methyladenosine, N methyladenosine, N2, N2-dimethylguanosine, N6-carbamoylthreonyladenosine, and pseudouridine | ||
| Su et al. [49] (2014) | LC-MS/MS | Severe sepsis | Sepsis vs. noninfected SIRS: |
| Uncomplicated sepsis | ↓ Lactitol dehydrate and S-phenyl-d-cysteine and ↑ in S-(3-methylbutanoyl)-dihydrolipoamide-E and N-non-anoyl glycine | ||
| Noninfected SIRS | Severe sepsis vs. uncomplicated sepsis: | ||
| Healthy controls | ↓ Glyceryl-phosphoryl-ethanolamine, Ne, Ne-dimethyl-lysine, phenylacetamide and d cysteine | ||
| Death within 24 hr: | |||
| ↓ S-(3-methylbutanoyl)-dihydrolipoamide-E, phosphatidylglycerol, glycerophosphocholine GPC, and S-succinyl glutathione | |||
| Kamisoglu et al. [30] (2015) | LC-MS/MS | Sepsis nonsurvivors | Sepsis and healthy control vs. LPS-induced endotoxemia vs. noninfected SIRS: |
| Sepsis survivors | ↑ 2-Hydroxybutyrate, mannose, bilirubin, and lipids | ||
| LPS-induced endotoxemia in healthy controls | Sepsis survivors vs nonsurvivors: | ||
| Noninfected SIRS | ↑ Acylcarnitines-carnitines were the most discriminatory metabolites | ||
| Mickiewicz et al. [51] (2014) | 1H NMR | Septic shock | Discriminatory metabolite between septic shock, SIRS, and healthy controls: |
| SIRS | 2 Hydroxybutyrate, lactate, histidine, phenylalaninephenylalanine, and arginine | ||
| Healthy controls | |||
| Mickiewicz et al. [52] (2015) | 1H NMR | Septic shock | Discriminatory metabolite between sepsis survivors and nonsurvivors: |
| ICU controls | 20 Metabolites differentiated the profiles of survivors and nonsurvivors | ||
| Garcia-Simon et al. [59] (2015) | 1H NMR | Septic shock | Discriminatory metabolite between sepsis survivors and nonsurvivors: |
| Arginine, methionine, glutamine, phenylalanine, glucose, ethanol, and hippurate showing differences between nonsurvivors and survivors | |||
| Liu et al. [53] (2016) | LC-MS/MS | Septic shock | Discriminatory metabolite: |
| 43 Significant metabolites varied in their levels when compared between survivors with nonsurvivors | |||
| 6 Primary discriminators: valine, leucine, isoleucine, citrulline, carnitine 2:0, and betanin | |||
| Ferrario et al. [54] (2016) | LC-MS/MS | Septic shock | Upregulated in nonsurvivors: |
| Polyamines, glucogenic amino acids, and kynurenine | |||
| Downregulated in nonsurvivors: | |||
| Phosphatidylcholines and lysophosphatidylcholines | |||
| Neugebauer et al. [45] (2016) | LC-MS/MS | SIRS | Discriminatory metabolite: |
| Sepsis | Acylcarnitines, glycerophospholipids and sphingolipids were altered in sepsis compared to SIRS | ||
| Cambiaghi et al. [62] (2018) | LC-MS/MS | Septic shock | Discriminatory metabolite: |
| Alteration in the lipidome of nonsurvivors was found | |||
| PC aa C42:6, PC aa C40:6, and lyso-PC species | |||
| Dalli et al. [55] (2017) | LC-MS/MS | Septic shock | Discriminatory metabolite: |
| Elevation in the levels prostaglandin F2α, leukotriene B4, resolvin E1 resolvin D5, and 17R-protectin D1 were found in nonsurvivors | |||
| Chung et al. [56] (2019) | UHPLC-MS | Septic shock | Discriminatory metabolite: |
| A significantly higher level of plasma acetylcarnitine was found in sepsis nonsurvivors when compared with survivors | |||
| Liu et al. [58] (2019) | 1H NMR | Septic shock | Discriminatory metabolite: |
| The concentrations of alanine, glutamate, glutamine, methionine, aromatic amino acids, ketone bodies, 3-hydroxybutyrate, and acetate were increased in the nonsurvivors as compared to the survivors | |||
| N-acetyl glycoprotein level was found decreased in nonsurvivors | |||
| Jaurila et al. [40] (2020) | 1H NMR | Sepsis | Discriminatory metabolite: |
| Healthy controls | Significantly higher serum lactate and citrate concentrations in nonsurvivors compared with survivors | ||
| Liang et al. [39] (2016) | LC-MS/MS | Septic shock | Discriminatory metabolite: |
| Healthy controls | Sphingosine, 5 methylcytidine, 3 dehydrocarnitine, 4 acetamido-2-aminobutanoic acid and phenyllactic acid in the septic shock subjects were significantly different from the controls | ||
| Feng et al. [48] (2022) | LC-MS/MS | Multiple trauma (non-SIRS) | Discriminatory metabolite: |
| Sepsis | 9 Potential biomarkers, namely, acrylic acid, 5-amino-3-oxohexanoate, 3b-hydroxy-5-cholenoic acid, cytidine, succinic acid semialdehyde, PE [P-18:1(9Z)/16:1(9Z)], sphinganine, uracil, and uridine were identified | ||
| Mecatti et al. [36] (2018) | LC-MS/MS | Septic shock | Discriminatory metabolite: |
| Healthy controls | FAs and phospholipids detected in plasma and erythrocytes could signal sepsis vs. nonsepsis | ||
| Lyso-PCs and SMs were downregulated, whereas the saturated and unsaturated PCs were upregulated in the plasma and erythrocytes of septic patients | |||
| Pandey et al. [41] (2021) | 1H NMR | Septic shock | Discriminatory metabolite: |
| Healthy controls | The potential biomarkerspotential biomarkers for septic shock are lactate, 3 hydroxybutyrate, 3 hydroxyisovalerate, proline, 1,2 propanediol, creatine, glycine, phenylalanine, and myoinositol, bile, NAG, and VLDL, which were significantly upregulated in septic shock patients, whereas citrate, carnitine, HDL, LDL, and lipoprotein with phosphocholine head group were downregulated in septic shock patients | ||
| Septic shock with comorbid conditions (diabetes and hypertension) | |||
| Septic shock with primary diagnosis (respiratory illness and encephalopathy) | |||
| Pandey et al. [57] (2023) | 1HNMR | Septic shock pretreatment | Discriminatory metabolite: |
| Septic shock posttreatment | The study showed time-dependent metabolite alteration in ketone bodies, amino acids, choline, and NAG in patients undergoing treatment. | ||
| Cambiaghi et al. [65] (2017) | LC- MS/MS | Treatment response in septic shock | Discriminatory metabolite: |
| Lipidome alterations play an important role in individual patients' responses to infection | |||
| Furthermore, alanine indicates a possible alteration in the glucose-alanine cycle in the liver, providing a different picture of liver functionality from bilirubin | |||
| Kauppi et al. [50] (2016) | LC-MS/MS | Sepsis | Discriminatory metabolite: |
| Healthy controls | 6 Metabolites were identified for bacteremic sepsis | ||
| Winkler et al. [61] (2018) | LC- MS/MS | Sepsis | Discriminatory metabolite: |
| SDMA and ADMA associated with sepsis mortality | |||
| Huang et al. [60] (2019) | LC- MS/MS | Septic shock | Discriminatory metabolite: |
| Phenylalanine- and leucine-defined risk classifications provide metabolic information with prognostic value for patients with severe infection | |||
| Li et al. [44] (2023) | LC-MS/MS | Sepsis | Discriminatory metabolite: |
| Healthy controls | 3-Phenyl lactic acid, N-phenylacetylglutamine, phenylethylamine, traumatin, xanthine, methyl jasmonate, indole, l-tryptophan | ||
| Chen et al. [66] (2022) | LC-MS/MS | Sepsis | Discriminatory metabolite: |
| Healthy controls | 73 Differentially expressed metabolites that could predict sepsis were identified. | ||
| Pandey et al. [42] (2022) | 1H NMR | Septic shock survivor (male/female) | Discriminatory metabolite: |
| Septic shock nonsurvivor (male/female) | The energy-related metabolites, ketone bodies, choline, and NAG were found to be primarily responsible for differentiating survivors and nonsurvivors | ||
| The sex-based mortality stratification identified a female-specific association of the anti-inflammatory response, innate immune response, and β oxidation, and a male-specific association of the proinflammatory response to septic shock | |||
| Puskarich et al. [64] (2015) | LC- MS/MS | Carnitine treatment response in septic shock | Drug responsive metabolite: |
| Responsive towards carnitine treatment | |||
| Evans et al. [63] (2019) | LC- MS/MS | Carnitine treatment response in septic shock | Drug responsive metabolite: |
| Metabolic signature of L-carnitine-treated nonsurvivors is associated with a severity of illness (e.g., vascular inflammation) that is not routinely clinically detected | |||
| Pandey et al. [43] (2023) | 1H NMR | Treatment response in septic shock | Drug responsive metabolite: |
| 3 Hydroxybutyrate, lactate, and phenylalanine which were lower, whereas glutamate and choline higher in patients showing responsiveness |
NMR, nuclear magnetic resonance; CLP, cecal ligation and puncture; LC-MS/MS, liquid chromatography coupled mass spectrometry; LPS, lipopolysaccharide; TAG, triacylglyceride; FA, fatty acid; GPC, glycerophosphocholine; TCA, tricarboxylic acid.
NMR, nuclear magnetic resonance; SIRS, systemic inflammatory response syndrome; MODS, multiorgan dysfunction syndrome; FA, fatty acid; BCAA, branched-chain amino acid; TAG, triacylglyceride; LDL, low-density lipoprotein; VLDL, very low-density lipoprotein; ALI, acute liver injury; LC-MS/MS, liquid chromatography coupled mass spectrometry; LPS, lipopolysaccharides; AA, arachidonic acid; PGE2, prostaglandin E2; 11-HETE, 11-hydroxyeicosatetraenoic acid; TXB2, thromboxane B2; GPC, glycerophosphocholine; GPE, glycerophosphoethanolamine; ICU, intensive care unit; PC, phosphatidylcholine; UHPLC-MS, ultrahigh performance liquid chromatography coupled with mass spectrometry; SM, sphingomyelin; NAG, N-acetylglycoprotein; HDL, high-density lipoprotein; SDMA, symmetric dimethylarginine; ADMA, assymmetric dimethylarginine.
Adapted from Pandey [
