肠道微生态如何和宿主作用导致IBD机制尚不清楚。我们前期研究发现TNF-α可下调DRA破坏肠上皮屏障，而用DRA干预DSS结肠炎小鼠可修复肠上皮屏障，减轻肠道炎症；同时肠菌A.muciniphia等上调，菌群多样性改变。有研究发现DRA可转运肠菌代谢产物SCFA，我们也证实SCFA干预DSS结肠炎小鼠后DRA表达增加，提示肠菌及SCFA与DRA存在相关性。结合前期研究和预实验结果，我们提出肠菌及SCFA可通过DRA影响肠上皮屏障。本研究拟利用肠organoids这一有力工具，通过临床、动物和细胞实验，证实肠菌及SCFA调节DRA的表达和功能，并通过激活/阻断TNF-α/NF-κB途径和启动子激活探讨肠菌及SCFA调控DRA的分子机制，通过沉默或抑制DRA证实SCFA通过其转运而发挥作用，阐明肠菌及SCFA-TNF-α/NF-κB-DRA在肠上皮屏障中的地位及作用机制，以期寻找潜在干预靶点。

Intestinal microbiota is closely related to inflammatory bowel disease (IBD), but how they act with the host to lead to the development of IBD remains unclear. We previously identified that TNF-α can damage the intestinal epithelial barrier through downregulating Slc26a3 (DRA)，whereas intervention with DRA in DSS-induced colitis mice can improve the expression of tight junction (TJ), leading to repairment of intestinal epithelial barrier and eventually alleviate intestinal inflammation. In addition, we also found the intestinal bacteria such as A.muciniphia were upregulated, and the diversity of bacterial flora was also changed. Furthermore, previous studies demonstrated that DRA can transport short-chain unsaturated fatty acids (SCFA), the main metabolite product of dietary fiber fermented by intestinal flora. We also confirmed that the expression of DRA was significantly increased after SCFA treatment in DSS-induced colitis mice, which suggesting that there are correlations among enterobacteria, SCFA and DRA. Based on previous studies and our preliminary experimental results, we pose a hypothesis that intestinal bacteria such as A.muciniphia and the metabolite SCFA can affect intestinal epithelial barrier by regulating DRA. Therefore, we want to clarify that intestinal bacteria and the metabolite SCFA can regulate the expression and function of DRA in a series of clinical, animal and cellular experiments using intestinal organoids as a powerful tool. At the same time, the possible signal pathway and molecular mechanisms of intestinal bacteria and SCFA in regulating DRA are explored by activating/blocking TNF-α/NF-κB pathway and the promoter activation analysis at cellular level. The role of SCFA in transporting and regulating DRA is also confirmed by silencing or inhibiting DRA in cells. In this way, we want to illustrate the role and mechanisms of intestinal bacteria and SCFA-TNF-α/NF-κB-DRA involved in intestinal epithelial barrier in IBD, and to explore the potential intervention targets of IBD in future.