A metabolomic approach for diagnosis of experimental sepsis

Abstract

Background

The search for reliable diagnostic biomarkers of sepsis remains necessary. Assessment of global metabolic profiling using quantitative nuclear magnetic resonance (NMR)-based metabolomics offers an attractive modern methodology for fast and comprehensive determination of multiple circulating metabolites and for defining the metabolic phenotype of sepsis.

Objective

To develop a novel NMR-based metabolomic approach for diagnostic evaluation of sepsis.

Methods

Male Sprague–Dawley rats (weight 325–375 g) underwent cecal ligation and puncture (n = 14, septic group) or sham procedure (n = 14, control group) and 24 h later were euthanized. Lung tissue, bronchoalveolar lavage (BAL) fluid, and serum samples were obtained for 1H NMR and high-resolution magic-angle spinning analysis. Unsupervised principal components analysis was performed on the processed spectra, and a predictive model for diagnosis of sepsis was constructed using partial least-squares discriminant analysis.

Results

NMR-based metabolic profiling discriminated characteristics between control and septic rats. Characteristic metabolites changed markedly in septic rats as compared with control rats: alanine, creatine, phosphoethanolamine, and myoinositol concentrations increased in lung tissue; creatine increased and myoinositol decreased in BAL fluid; and alanine, creatine, phosphoethanolamine, and acetoacetate increased whereas formate decreased in serum. A predictive model for diagnosis of sepsis using these metabolites classified cases with sensitivity and specificity of 100%.

Conclusions

NMR metabolomic analysis is a potentially useful technique for diagnosis of sepsis. The concentrations of metabolites involved in energy metabolism and in the inflammatory response change in this model of sepsis.

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Acknowledgments

We thank Palmira Villa and Elena Sáez of the NMR Center of Complutense University of Madrid for NMR spectra acquisition, and Instituto de Salud Carlos III (FIS 08/1726), Spanish MICINN (SAF2008-05412), PI-NET European Network (ITN-FP7-264864), Fundación Mutua Madrileña (AP/67842009), and Lilly Foundation Spain.

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Correspondence to José A. Lorente.

Additional information

J. L. Izquierdo-García and N. Nin contributed equally to the manuscript.

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Izquierdo-García, J.L., Nin, N., Ruíz-Cabello, J. et al. A metabolomic approach for diagnosis of experimental sepsis. Intensive Care Med 37, 2023–2032 (2011). https://doi.org/10.1007/s00134-011-2359-1

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Keywords

  • Sepsis
  • Metabolomics
  • Chemometrics
  • Diagnosis
  • Biomarker
  • Spectroscopy