脱硫弧菌在炎症相关性结肠癌发生中的作用机制

肠道菌群失调在炎症性肠病（IBD）及炎症相关性结肠癌（CAC）发生发展中具有重要作用。我们前期研究发现，在CAC模型小鼠肠道中脱硫弧菌显著增多，且以乳酸杆菌为主的益生菌复合物预防性治疗可显著降低脱硫弧菌含量，减少肠道肿瘤形成。进一步研究发现肠道粘膜脱硫弧菌含量与COX2－PGE2－CXCR2信号通路具有显著相关性。基于此，我们推测脱硫弧菌可能通过激活CXCR2信号轴来发挥其促炎促癌作用。因此，本项目拟利用脱硫弧菌定植伪无菌鼠以及化学诱导方法建立脱硫弧菌诱导的IBD－CAC小鼠模型，研究脱硫弧菌在IBD－CAC发生及发展中的具体作用，并对脱硫弧菌与COX2－PGE2－CXCR2信号通路的关系做进一步探索。本项目的完成有助于阐明在炎症性肠病恶性转化过程中脱硫弧菌的具体作用及内在机制。借此丰富肠道菌群与炎症／肿瘤调控网络理论，为IBD恶性转化治疗提供新策略和理论依据。

Intestinal flora plays a fundamental role in the initiation and progression of inflammatory bowel disease and Colitis-Associated Colorectal Cancer (CAC). Our previous study indicated that the Desulfovibrio was significantly increased in the colon tissues of CAC model mice, and prophylactic treatment with Lactobacillus-based probiotics could significantly reduce the relative abundance of Desulfovibrio and reduce the tumor formation. Further study demonstrated that Desulfovibrio was significantly correlated with COX2-PGE2-CXCR2 signaling pathway. Therefore, our project intends to establish a Desulfovibrio-CAC mouse model using the pseudo-sterile mice and chemical-induced methods and figures out the critical role of the Desulfovibrio in the initiation and progression of CAC. The downstream mechanisms concerning Desulfovibrio and COX2-PGE2-CXCR2 signaling pathway are necessary to be elucidated. The completion of this project will be instrumental to clarify the specific relationship between Desulfovibrio and colonic tumorigenesis. The project also can enrich the theory of regulatory network inculding gut microbiota and inflammation / tumor, and provide new strategies and theoretical basis for the treatment of IBD-CAC transformation.