炎症性肠病患者并发艰难梭菌感染预后差，死亡率和结肠切除率高，而常规抗生素治疗效果不理想。艰难梭菌毒素B（TcdB）是艰难梭菌感染后的致病关键毒素因子，可通过受体介导的内吞作用进入细胞，导致细胞变圆、最终死亡。Wnt受体中的卷曲蛋白家族成员（FZDs）也是肠上皮TcdB受体。TcdB与Wnt竞争性结合FZDs，TcdB与FZDs的结合抑制Wnt信号通路。我们发现，Syndecan-1(Sdc1)胞外段HS链脱落在炎症性肠病发病中发挥重要作用。而Sdc1被发现在骨髓瘤细胞可调控Wnt信号及其受体FZD内化。那么，Sdc1在肠上皮细胞是否也有类似作用尚无研究。在前期研究基础上，本项目拟通过毒素刺激、Sdc1基因突变、HS合成酶基因突变、RNA干扰、过表达、干预R-spodin/LGR4信号通路等多重途径验证Sdc1对CDI发生关键环节的影响，探讨IBD患者并发CDI的相关机制。

Patients with inflammatory bowel disease complicated by Clostridium difficile infection have a poor prognosis, high mortality and colon resection rate, while the conventional antibiotic treatment is not satisfactory. Clostridium difficile toxin B (TcdB) is a key disease-causing toxin factor after C. difficile infection and can enter cells through receptor-mediated endocytosis, resulting in rounding of the cells and eventually death. Frizzled family members (FZDs) in Wnt receptors are also intestinal epithelial TcdB receptors. TcdB competes with Wnt for binding to FZDs, and binding of TcdB to FZDs inhibits Wnt signaling. We found that Syndecan-1 (Sdc1) extracellular HS chain shedding plays an important role in the development of inflammatory bowel disease. Sdc1 was found to regulate Wnt signaling and its receptor FZD internalization in myeloma cells. So, Sdc1 in the intestinal epithelial cells have a similar role has not been studied. Based on the previous studies, this project intends to verify the impact of Sdc1 on key CDI occurrence through multiple pathways including toxin stimulation, Sdc1 mutation, HS synthetase gene mutation, RNA interference, overexpression and intervention of R-spodin / LGR4 signaling pathway. Explore the mechanism of CDI in patients with IBD.