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.

在本研究项目中，利用t-RFLP分析显示了炎症性肠病患者肠道微生物区系的新方面，即溃疡性结肠炎患者的t-RFLP谱显示出与正常人明显不同的独特谱。用上皮电阻法测定二次胆汁酸阻断粘膜屏障的机制主要依赖于氧自由基的合成，推测XO参与了上信号通路，ERK1/2、PI3K、p38MAPK和MLCK参与了ROS合成的下游信号通路。将UGT1A3基因导入Caco-2细胞，可抑制胆石酸诱导的IL-8mRNA表达，提示溃疡性结肠炎中独特的肠道微生物区系所产生的胆汁酸成分改变可能在IBD的发病机制中发挥了新的作用。

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.