GCMS-based metabolomic study in mice with colitis induced by dextran sulfate sodium

Authors

  • Yuuki Shiomi MD,

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
    Search for more papers by this author
  • Shin Nishiumi PhD,

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
    2. The Integrated Center for Mass Spectrometry, Graduate School of Medicine, Kobe University, Kobe, Japan
    Search for more papers by this author
  • Makoto Ooi MD,

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
    Search for more papers by this author
  • Naoya Hatano PhD,

    1. The Integrated Center for Mass Spectrometry, Graduate School of Medicine, Kobe University, Kobe, Japan
    Search for more papers by this author
  • Masakazu Shinohara MD, PhD,

    1. The Integrated Center for Mass Spectrometry, Graduate School of Medicine, Kobe University, Kobe, Japan
    Search for more papers by this author
  • Tomoo Yoshie MD,

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
    Search for more papers by this author
  • Yasuyuki Kondo MD,

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
    Search for more papers by this author
  • Keisuke Furumatsu MD,

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
    Search for more papers by this author
  • Hideyuki Shiomi MD,

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
    Search for more papers by this author
  • Hiromu Kutsumi MD, PhD,

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
    Search for more papers by this author
  • Takeshi Azuma MD, PhD,

    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
    Search for more papers by this author
  • Masaru Yoshida MD, PhD

    Corresponding author
    1. Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan
    2. The Integrated Center for Mass Spectrometry, Graduate School of Medicine, Kobe University, Kobe, Japan
    3. Division of Metabolomics Research, Graduate School of Medicine, Kobe University, Kobe, Japan.
    • Division of Metabolomics Research, Division of Gastroenterology, The Integrated Center for Mass Spectrometry, Graduate School of Medicine, Kobe University, 7-5-1, Chuo-ku, Kusunoki-cho, Kobe, Hyogo, 650-0017, Japan
    Search for more papers by this author

Abstract

Background:

Metabolomics provides data about all the metabolic processes of a cell or organism. So far, the changes that occur in the levels of metabolites during the development of colitis have not been fully elucidated. Here we examined the changes of metabolite levels in the serum and colon tissue of colitis mice using gas chromatography mass spectrometry (GC/MS) with the aim of achieving a detailed understanding of the pathogenesis of inflammatory bowel disease (IBD).

Methods:

To induce colitis, C57BL/6J mice were administered 3.0% dextran sulfate sodium (DSS) in their drinking water for 5 days and were subsequently given drinking water alone.

Results:

A total of 77 and 92 metabolites were detected in serum and colon tissue, respectively, and among the metabolites the compositions of TCA cycle intermediates and amino acids changed depending on the degree of colitis. Then, partial least square discriminant analysis (PLS-DA), a multiple classification analysis, showed distinct clustering and clear separation of the groups according to the degree of colitis. Furthermore, PLS-DA loadings plots revealed that succinic acid, indole-3-acetic acid, glutamic acid, and glutamine were the main contributors to the separation of each stage of colitis. In addition, it was revealed that supplementation with glutamine, the level of which was significantly decreased in the acute phase of colonic inflammation, attenuated colitis induced by DSS.

Conclusions:

Our results suggest that metabolomics is capable of representing the various degrees of colitis, and our findings will aid in the discovery of therapeutic agents for IBD and other inflammatory disorders by metabolomic approaches. (Inflamm Bowel Dis 2011;)

Ancillary