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. 2021 Dec 21;12(1):1. doi: 10.3390/metabo12010001

Table 1.

Metabolomics-assisted diagnosis of sepsis in critically ill patients.

Age
(Sample Size)		 APACHE-II Score Samples Since Admission Methods Major Findings in Sepsis Group Interpretation Citation
Serum Plasma Others Metabolic Pathways Decreased Increased
N/A
(102)
vs.
N/A
(56)		 N/A
vs.
N/A		 ✓
D1		 Targeted (LC-MS/MS) At D1 Patients with sepsis had increased ceramides, but decreased phospholipids when compared to patients without sepsis [8]
Fatty acids

  • Ceramides

 C23:0, C24:0

  • Ceramides

 C16:0, C18:0, C20:0, C22:1, C24:1, and total form
Phospholipids

  • LysoPC
T: 64 ± 11
(30)
vs.
67 ± 10
(33)
V: 64 ± 15
(39)
vs.
67 ± 10
(41)		 23 ± 8
vs.
18 ± 7
26 ± 9
vs.
19 ± 7		 ✓
within 24 h/ at onset of SIRS		 Targeted
(LC-MS/MS)		 Fatty acids -

  • AC C3, C5, C6 (C4:1-DC), C8, C10:1

 Fatty acids and phospholipids are potential markers for discriminating sepsis from SIRS [9]
Phospholipids -

  • PCaa

  • PCae
64 ± 17 (35)
vs.
59 ± 19 (15)		 22 ± 7
vs.
11 ± 9		 ✓
within
24 h		 Targeted
(LC-MS/MS) 		Amino acids and amine

  • S-phenyl-d-cysteine

  • N-nonanoyl glycine

 Amino acids and lactitol dihydrate could differentiate sepsis from SIRS [10]
Others

  • Lactitol dihydrate

  • S-(3-methyl-butanoyl)-dihydrolipoamide-E
57 ± 22 (35)
vs.
47 ± 13 (14)		 18 ± 8
vs.
9 ± 3		 ✓
within
24 h		 Targeted
(LC-MS/MS)		 Amino acids and amine

  • Anserine

  • Lysine

  • Phosphoethano-lamine

  • δ-Hydroxylysine

  • Ethanolamine

  • Homocitrulline

  • Cystathionine

 Critically ill patients with sepsis had a wide range of amino acid spectral changes that differ from SIRS [11]
T: 70 ± 17 (123)
vs.
63 ± 16
(42)
V: 64 ± 24
(59)
vs.
60 ± 18
(2)		 11 ± 6
vs.
11 ± 8
13 ± 11
vs.
9 ± 6		 ✓
within 24 h		 Targeted
(LC-MS/MS)		 Amino acids and amine -

  • Serine

  • Aspartate

  • Phenylalanine

  • Dimethylarginine

  • Acetylornithine

  • Kynurenine

  • Spermine

  • Spermidine

 Amino acids, fatty acids, and phospholipids can potentially be used as sepsis biomarkers [12]
Fatty acids

  • AC C16:2(OH)

  • AC C6(C4:1-DC)
Phospholipids

  • PCaa C32:2, C36:6, C40:4, C42:6

  • PCae

  • LysoPCa

  • SM C20:2, C22:3, C24:0, C26:1

  • SM-OH C22:1, C24:1

  • PCaaC32:0

  • SM C16:1
56 ± 18
(20)
vs.
58 ± 11
(20)		 15 ± 6
vs.
N/A		 ✓
within
36 h		 Targeted
(LC-MS and GC-MS)		 Phospholipids

  • LysoPC

  • PC


C16:0/20:1,
 C16:0/20:3

  • SM

  • PC

 C15:0/18:2, C16:0/18:1,
 C16:0/18:2,
 C16:0/20:5		 Fatty acids and phospholipids detected in plasma and erythrocytes could signal sepsis vs. non-sepsis [13]
Erythrocytes
✓
within
36 h		 GC-MS Fatty acids

  • n-3 PUFA

 DPA (C22:5 n-3)
 DHA (C22:6 n-3)

  • Total MUFA

  • Oleic (C18:1 n-9)
Phospholipids

  • LysoPC

  • PC C15:0/18:2

  • SM

  • PC

 C16:0/18:2,
 C16:0/20:4, C16:0/20:5

  • PS

Continuous data are presented in mean ± SD; N/A not available. Abbreviations: a, acyl; aa, diacyl; ae, acyl-akyl; AC, acylcarnitine; APACHE-II score, Acute Physiology and Chronic Health Evaluation-II score; C, number of carbons in the fatty acid side chain; DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; LysoPC, lysophosphatidylcholine; LC-MS/MS, liquid chromatography-tandem mass spectrometry; MUFA, monounsaturated fatty acid; PC, phosphatidylcholine; PS, phosphatidylserine; PUFA, polyunsaturated fatty acid; SM, sphingomyelin; SIRS, systemic inflammatory response syndrome; T, training dataset; V, validation dataset.