Alterations in Docosahexaenoic Acid-Related Lipid Cascades in Inflammatory Bowel Disease Model Mice

Abstract

Background

Inflammatory bowel disease (IBD) is an intestinal disorder, involving chronic and relapsing inflammation of the digestive tract. Dysregulation of the immune system based on genetic, environmental, and other factors seems to be involved in the onset of IBD, but its exact pathogenesis remains unclear. Therefore, radical treatments for ulcerative colitis and Crohn’s disease remain to be found, and IBD is considered to be a refractory disease.

Aims

The aim of this study is to obtain novel insights into IBD via metabolite profiling of interleukin (IL)-10 knockout mice (an IBD animal model that exhibits a dysregulated immune system).

Methods

In this study, the metabolites in the large intestine and plasma of IL-10 knockout mice were analyzed. In our analytical system, two kinds of analysis (gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry) were used to detect a broader range of metabolites, including both hydrophilic and hydrophobic metabolites. In addition, an analysis of lipid mediators in the large intestine and ascites of IL-10 knockout mice was carried out.

Results

The levels of a variety of metabolites, including lipid mediators, were altered in IL-10 knockout mice. For example, high large intestinal and plasma levels of docosahexaenoic acid (DHA) were observed. In addition, arachidonic acid- and DHA-related lipid cascades were upregulated in the ascites of the IL-10 knockout mice.

Conclusions

Our findings based on metabolite profiles including lipid mediators must contribute to development of researches about IBD.

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Funding

This study was supported by a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science (JSPS) (16H05227) [M.Y.]; a Grant-in-Aid for Scientific Research (C) from the JSPS (26350960) [S.N.]; the AMED-CREST by the Japan Agency for Medical Research and Development (AMED) (17gm0710013h0004) [S.N., M.Y.]; and the Special Coordination Funds for Promoting Science and Technology, Creation of Innovation Centers for Advanced Interdisciplinary Research Areas (Innovative Bioproduction Kobe) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan [M.Y.].

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Correspondence to Shin Nishiumi or Masaru Yoshida.

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Nishiumi, S., Izumi, Y. & Yoshida, M. Alterations in Docosahexaenoic Acid-Related Lipid Cascades in Inflammatory Bowel Disease Model Mice. Dig Dis Sci 63, 1485–1496 (2018). https://doi.org/10.1007/s10620-018-5025-4

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Keywords

  • IBD
  • IL-10 knockout mice
  • Metabolite profiling
  • Mass spectrometry