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Application of LC-MS-based metabolomics method in differentiating septic survivors from non-survivors

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Abstract

Septic shock is the most severe form of sepsis, which is still one of the leading causes of death in the intensive care unit (ICU). Even though early prognosis and diagnosis are known to be indispensable for reaching an optimistic outcome, pathogenic complexities and the lack of specific treatment make it difficult to predict the outcome individually. In the present study, serum samples from surviving and non-surviving septic shock patients were drawn before clinical intervention at admission. Metabolic profiles of all the samples were analyzed by liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. One thousand four hundred nineteen peaks in positive mode and 1878 peaks in negative mode were retained with their relative standard deviation (RSD) below 30 %, in which 187 metabolites were initially identified by retention time and database in the light of the exact molecular mass. Differences between samples from the survivors and the non-survivors were investigated using multivariate and univariate analysis. Finally, 43 significantly varied metabolites were found in the comparison between survivors and non-survivors. Concretely, metabolites in the tricarboxylic acid (TCA) cycle, amino acids, and several energy metabolism-related metabolites were up-regulated in the non-survivors, whereas those in the urea cycle and fatty acids were generally down-regulated. Metabolites such as lysine, alanine, and methionine did not present significant changes in the comparison. Six metabolites were further defined as primary discriminators differentiating the survivors from the non-survivors at the early stage of septic shock. Our findings reveal that LC-MS-based metabolomics is a useful tool for studying septic shock.

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Acknowledgments

We sincerely thank to the support of the University of Paris-XIII and the help from the Jean Verdier Hospital. The study has been supported by the key foundation (No. 21435006) from the National Natural Science Foundation of China.

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Authors and Affiliations

  1. Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, Liaoning, 116023, China

    Zhicheng Liu, Peiyuan Yin & Guowang Xu

  2. Sorbonne Paris Cité, Laboratoire de Chimie, Structures et Propriétés de Biomateriaux et d’Agents Therapeutiques, UMR 7244, Université Paris 13, Rue de Chablis 1, 93000, Bobigny, France

    Zhicheng Liu, Roland Amathieu & Philippe Savarin

  3. Intensive Care Unit, Jean Verdier Teaching Hospital, AP-HP, 93140, Bondy, France

    Roland Amathieu

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  1. Zhicheng Liu
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  5. Guowang Xu
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Correspondence to Guowang Xu.

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The Institutional Review Board of Jean Verdier University Hospital approved the protocol and the French Research Delegation Office accepted the creation of a dedicated bio-collection for the patients included in the protocol. The CNIL (National Informatics and Liberty Commission) also approved the creation of both bio-collection and database. Depending of the mental status of the patient, the written consent was obtained directly from the patient at inclusion or from the Person of Confidence designed by the patient (pre-emptively) or by the family relatives. In case of survival, a secondary written consent from the patient was systematically seek.

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The authors declare that they have no conflict of interest.

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Liu, Z., Yin, P., Amathieu, R. et al. Application of LC-MS-based metabolomics method in differentiating septic survivors from non-survivors. Anal Bioanal Chem 408, 7641–7649 (2016). https://doi.org/10.1007/s00216-016-9845-9

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  • DOI: https://doi.org/10.1007/s00216-016-9845-9

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