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.

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。

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.