Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Dig Dis Sci. 2018 Jun;63(6):1485-1496. doi: 10.1007/s10620-018-5025-4. Epub 2018 Mar 21.
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.
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).
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.
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.
Our findings based on metabolite profiles including lipid mediators must contribute to development of researches about IBD.
炎症性肠病（IBD）是一种肠道疾病，涉及消化道的慢性和复发性炎症。基于遗传、环境和其他因素的免疫系统失调似乎与 IBD 的发病有关，但确切的发病机制尚不清楚。因此，溃疡性结肠炎和克罗恩病的根治方法仍有待发现，IBD 被认为是一种难治性疾病。
本研究旨在通过白细胞介素（IL）-10 敲除小鼠（一种表现出免疫系统失调的 IBD 动物模型）的代谢组学分析，深入了解 IBD。
在这项研究中，分析了 IL-10 敲除小鼠的大肠和血浆中的代谢物。在我们的分析系统中，使用了两种分析方法（气相色谱/质谱法和液相色谱/质谱法）来检测更广泛的代谢物，包括亲水性和疏水性代谢物。此外，还对 IL-10 敲除小鼠的大肠和腹水的脂质介质进行了分析。
IL-10 敲除小鼠的多种代谢物水平发生了改变，包括脂质介质。例如，观察到高水平的二十二碳六烯酸（DHA）在大肠和血浆中。此外，IL-10 敲除小鼠的腹水中，花生四烯酸和 DHA 相关的脂质级联被上调。
我们基于包括脂质介质在内的代谢组学的发现，必将为 IBD 的研究做出贡献。
