UPLC-QTOF/MS based metabolomics reveals metabolic alterations associated with severe sepsis

Abstract

Severe sepsis (SS) remains among the leading causes of death in both developed and developing countries. There is an urgent need for accurate biomarkers for early diagnosis of SS. Non-targeted mass-spectrometry was used to characterize sensitive and economical peripheral biomarker(s) associated with the serum metabolome from SS patients. In this study, serum samples were obtained from healthy controls and age-matched patients with SS. Multivariate statistical analysis was performed, and the metabolites identified were studied in relation to subsequent intervention procedures by receiver operating characteristic curve analysis. Metabolic differences among SS and control subjects were identified based on orthogonal signal correction-partial least squares discriminant analysis. Sphingosine, 5-methylcytidine, 3-dehydrocarnitine, 4-acetamido-2-aminobutanoic acid and phenyllactic acid in the SS subjects were significantly different from the controls. Three metabolites comprising sphingosine, 5-methylcytidine and 3-dehydrocarnitine were selected as candidate biomarkers and validated in separate, independent patient cohorts. These metabolite markers hold great potential for further development of SS early diagnostic markers. These findings suggest mass-spectrometry serum metabolomics may possess great potential for early diagnosis of SS patients.