新近研究指出溃疡性结肠炎（UC）易感基因在肠道菌群影响UC的发病模式中意义重大。申请者前期研究发现，作为UC易感基因，腺癌中低表达离子转运体（DRA）与肠道炎症存在交互作用，且其下调可导致肠道厚壁菌/拟杆菌（F/B）比例失调。同时研究显示，不同种属间细菌数量及密度改变可使细菌间信号分子AI-2浓度变化，作用于宿主肠道免疫系统，参与炎症反应。然而DRA相关肠道F/B比例失调是否通过改变AI-2浓度在DRA调控肠道炎症中发挥重要作用及其调控途径未明。故本项目拟首先在UC患者标本中观察DRA表达与肠道F/B比例变化、AI-2浓度相关性；其次应用转基因小鼠研究DRA缺失影响F/B比例的机制，并研究F/B比例失调对AI-2浓度的调节及AI-2调控肠道炎症的免疫学途径；最后在肠道炎症中上调DRA表达，评估其对肠道菌群的调控作用及对肠道炎症的影响及机制，为寻找UC新的潜在干预靶点提供理论及实验依据。

Recent data suggest that ulcerative colitis (UC) susceptibility genes play an important role in dysbiotic gut microbiota associated pathogenesis of UC. Ion transporter down regulated in adenoma (DRA) is one of the UC susceptibility genes. Our previous data suggested that DRA acted reciprocally with intestinal inflammation. Moreover, down regulation of DRA resulted in gut microbiota dysbiosis characterized by disequilibrium of Firmicutes/Bacteroidetes ratio (F/B ratio). However, whether DRA-related F/B ratio disequilibrium plays role in regulating intestinal inflammation and the underlying mechanism is yet to be clear. Studies have shown that the concentration of bacterial signal molecules autoinducer 2 (AI-2) alters while the number and density of bacteria in different species changed. AI-2 subsequently acts on the host gut immune system and participate in gut inflammatory reaction. Therefore, this project aims to investigate the regulatory effect of DRA-associated gut microbiota dysbiosis on intestinal inflammation and the underlying mechanism as follow: Firstly, the relation among DRA expression, intestinal F/B ratio and AI-2 concentration is evaluated in colonic biopsies and stool specimens of UC patients and healthy control. Secondly, the regulatory mechanism of DRA deficiency on gut flora F/B ratio disequilibrium is studied in transgenic mice. The effect of imbalanced F/B ratio on the concentration of AI-2 and the immunological pathway of AI-2 in regulating intestinal inflammation is investigated at the cellular level. Finally, the effect of DRA upregulation during intestinal inflammation on intestinal flora and inflammation is studied, so as to provide theoretical and experimental evidence for seeking new potential therapeutic target of UC.