Introduction
Sepsis is an important cause of mortality and morbidity for preterm and hospitalized newborn babies. Today, no single test satisfies the criteria as being the ideal marker for the early diagnosis of neonatal sepsis. Analysis of the entire metabolome is a promising method for determining metabolic variations correlated with sepsis [1-6].
Metabolomics profiling and sepsis
Works on metabolomics concerning sepsis conducted on animals and humans of different ages (newborn and adults) have recently been published and are presented in Table 1. In septic patients compared to controls (in plasma and urine) it is possible to observe an increase of metabolites which are part of the oxidative metabolism of fatty acids (such as hydroxybutyrate, acylcarnitines and acetoacetate). Briefly stated, alterations in the glucose metabolism in critical conditions can be seen as a redistribution of glucose consumption from the mitochondrial oxidative phosphorylation to other metabolic pathways, such as the production of lactate and the pentose phosphate pathway. In the study by Fanos et al. [7] a combined approach based on both nuclear magnetic resonance (1)H-NMR) and gas-chromatography-mass spectrometry (GC-MS) techniques was used applied to neonatal infections. The study population included 25 neonates: 9 patients had a diagnosis of sepsis and 16 were healthy controls. This study showed a unique metabolic profile of the patients affected by sepsis compared to non-affected ones with a statistically significant difference between the two groups (p = 0.05). Mickiewicz et al [8] examined serum samples collected from 60 patients with septic shock (by Gram- and/or Gram+), 40 patients with SIRS and 40 healthy children by nuclear magnetic resonance spectroscopy spectra. Some of the metabolite concentrations were able to separate between patient groups. The main messages from the published studies are as follows. a) Metabolomics is able to early diagnose the infection (in some cases in preclinical conditions). b) Metabolomics is able to predict the outcome in single individuals and the AUC values are close to 1. c) Metabolomics appears to be a promising and useful instrument also in the diagnosis of sepsis. d) In the next future some easy tools, like urinary dipsticks, with the discriminant metabolites will be available in clinical settings, bedside.
Table 1.
Metabolomic studies that have analyzed the metabolic profiles of septic patients and of experimental animals (From ref. 6, mod.)
| Author | Population study | Sample | Metabolomic analysis | Metabolite alterations |
|---|---|---|---|---|
| Fanos et al. 2014 | 9 septic newborns vs 16 control newborns | Urine | GC-MS 1H NMR |
Lactate, glucose, maltose, ribitol, ribonic acid, pseudo-uridine, 2,3,4 trihydroxybutiric acid, 2-ketpgluconic acid, 3,4 hydroxybutanoic acid, 3,4,5 trihydroxypentanoic acid <(GC-MS) Acetate, acetone, citrate, creatinine, glycine, lactate, lysine, glucose (1H-NMR) |
| Mickiewicz et al. 2013 | 60 septic shock vs 40 SIRS vs 40 control pediatric patients | Serum | 1H-NMR | 2-hydroxybutyrate, 2-hydroxyisovalerate, lactate, glucose, 2-oxoisocaproate, creatine, creatinine, histidine, and phenylalanine |
| Schmerler et al. 2012 | 74 SIRS vs 69 septic vs 16 control human adults | Blood | LC-MS/MS | Acylcarnitines and glycerophosphatidylcholines |
| Mickiewitz et al. 2014 | 39 septic shock adult patients vs 20 ICU control patients | Serum | 1H-NMR | Isobutyrate, phenylalanine, 2 hydroxyisovalerate, myoinositol, acetylcarnitine, creatine, lactate, valine, arginine, methanol, glucose, glycine |
| Liu et al. 2010 | 40 septic vs control rats | Plasma | UPLC–Q-TOF-MS | Hypoxanthine, indoxyl sulfate, glucuronic acid, gluconic acid, proline, uracil, nitrotyrosine, uric acid and trihydroxy cholanoic acid |
| Lin et al. 2009 | 40 septic vs 20 control rats | Serum | 1H NMR | Lactate, alanine, acetate, acetoacetate, hydroxybutyrate and formate |
| Izquierdo-Garcìa et al. 2011 | 14 septic vs 14 control rats | Lung tissue, BALF and serum | 1H NMR | Alanine, creatine, phosphoethanolamine and myoinositol |
Conclusions
Present-day methods and procedures for the diagnosis of systemic neonatal infections are hindered by low sensitivity and long response times. Metabolomics is showing promise of becoming a most effective method, even in neonatology and paediatrics.
References
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