Involvement of intestinal microbiota derived secondary bile acids in the patho-physiology of inflammatory baowel disease and the expression of UGT by intestinal epithelial cells.

肠道微生物群衍生的次级胆汁酸参与炎症性鲍威尔病的病理生理学以及肠上皮细胞 UGT 的表达。

• 批准号: 14570462
• 负责人: FUJIYAMA Yoshihide
• 金额: $ 1.92万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570462/
• 关键词: IBD; intestinal micorbiota; bile acid; UGT; hyodeoxycholic acid; hodeoxcholic acid

In this research project, new aspect of intestinal microbiota in patients with inflammatory bowel disease has been demonstrated using t-RFLP analysis, i.e., the t-RFLP profile of patients with ulcerative colitis showed a unique profile which was apparently different from that of normal individuals. The major mechanism of interruption of mucosal barrier induced by secondary bile acids using ransepithelial electrical resistance determination method was depend on the synthesis of radical oxygen species, and it was estimated that XO was involved as upper signaling pathway and ERK1/2,PI3K,p38MAPK and MLCK were involved as down-stream signaling pathway of ROS synthesis. Transfection of UGT1A3 to CaCo-2 cells diminished IL-8 mRNA expression induced by lithocholic acid.These observations are indicative that alterations of bile acid composition produced by an unique intestinal microbiota profile in ulcerative colits might play a novel pathoetiological role in IBD.

在该研究项目中，使用t-RFLP分析证明了炎症性肠病患者肠道微生物群的新方面，即，溃疡性结肠炎患者的t-RFLP图谱显示出明显不同于正常个体的独特图谱。跨上皮电阻测定法表明，次级胆汁酸引起粘膜屏障功能障碍的主要机制是通过氧自由基的合成，推测XO是ROS合成的上游信号通路，ERK 1/2、PI 3 K、p38 MAPK和MLCK是ROS合成的下游信号通路。UGT 1A 3转染CaCo-2细胞可降低石胆酸诱导的IL-8 mRNA表达，提示溃疡性结肠炎肠道菌群独特的胆汁酸组成改变可能在IBD发病中发挥新的病理作用。

项目成果

Bamba T, Kanauchi O, Andoh A, Fujiyama Y.: "A new prebiotic from germinated barley foodstuff for nutraceutical treatment of ulcerative colitis"J. Gastroenterol Hepatol. 17(8). 818-824 (2002)

Bamba T、Kanauchi O、Andoh A、Fujiyama Y.：“一种来自发芽大麦食品的新型益生元，用于营养治疗溃疡性结肠炎”J.

Suppression of interleukin-1beta- and tumor necrosis factor-alpha-induced inflammatory responses by leukocytapheresis therapy in patients with ulcerative colitis.

通过白细胞去除疗法抑制溃疡性结肠炎患者的白细胞介素-1β-和肿瘤坏死因子-α诱导的炎症反应。

• 发表时间: 2004
• 期刊: J Gastroenterol. 39
• 作者: Andoh A他8名;Fujiyama Y(9番目)
• 通讯作者: Fujiyama Y(9番目)

B1-B cells are the main antigen presenting cells in CpG-ODN-stimulated peritoneal exudate cells

• DOI: 10.1111/j.1348-0421.2005.tb03633.x
• 发表时间: 2005-01-01
• 期刊: MICROBIOLOGY AND IMMUNOLOGY
• 影响因子: 2.6
• 作者: Bamba, H;Ishigaki, H;Ogasawara, K
• 通讯作者: Ogasawara, K

Andoh A 他3名 Fujiyama Y(4番目): "Epimorphin expression in human colonic myofibroblasts."Int J Mol Med.. 13巻1号. 57-61 (2004)

Andoh A 和其他 3 人 Fujiyama Y（第 4 期）：“人结肠肌成纤维细胞中的表吗啡表达。” Int J Mol Med.. Vol. 13，No. 1. 57-61 (2004)

Ogawa A 他4名 Fujiyama Y(5番目): "Neutralization of interleukin-17 aggravates dextransulfate sodium-induced colitis in mice."Clin Immunol.. 110巻1号. 55-62 (2004)

Okawa A 和其他 4 人 Fujiyama Y（第 5 期）：“白细胞介素 17 的中和会加重小鼠右旋硫酸钠诱导的结肠炎。”Clin Nutrition.. Vol. 110，No. 1. 55-62 (2004)