title: 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 (1)H 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.
authors: Instituto de Estudios Biofuncionales, Universidad Complutense de Madrid, Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors: José L
authors: JL
authors: Izquierdo-García
authors: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Hospital Universitario de Getafe, Madrid, Spain.
authors: Nicolás
authors: N
authors: Nin
authors: Instituto de Estudios Biofuncionales, Universidad Complutense de Madrid, Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors: Jesús
authors: J
authors: Ruíz-Cabello
authors: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Hospital Universitario de Getafe, Madrid, Spain.
authors: Yeny
authors: Y
authors: Rojas
authors: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Hospital Universitario de Getafe, Madrid, Spain.
authors: Marta
authors: M
authors: de Paula
authors: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Hospital Universitario de Getafe, Madrid, Spain.
authors: Sonia
authors: S
authors: López-Cuenca
authors: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Hospital Universitario de Getafe, Madrid, Spain.
authors: Luis
authors: L
authors: Morales
authors: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Hospital Universitario de Getafe, Madrid, Spain.
authors: Leticia
authors: L
authors: Martínez-Caro
authors: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Hospital Universitario de Getafe, Madrid, Spain.
authors: Pilar
authors: P
authors: Fernández-Segoviano
authors: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Hospital Universitario de Getafe, Madrid, Spain.
authors: Andrés
authors: A
authors: Esteban
authors: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain. jlorente.hugf@salud.madrid.org.|Hospital Universitario de Getafe, Madrid, Spain. jlorente.hugf@salud.madrid.org.|Department of Critical Care, Hospital Universitario de Getafe, 28905, Madrid, Spain. jlorente.hugf@salud.madrid.org.
authors: José A
authors: JA
authors: Lorente
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D016018:Least-Squares Analysis; D008168:Lung / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008954:Models, Biological; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D015415:Biomarkers