具核梭杆菌（Fn）作为肠道核心致癌菌，其能否在诱导细胞癌变过程中存在基因突变选择性尚不清楚。我们前期大样本检测发现Fn在KRAS基因突变患者癌组织中定植显著增多且更易感KRAS G12D突变位点。为此，在成功构建Kras LSL-G12D/Vilin-Cre肠上皮细胞特异活化KRAS小鼠模型的基础上，拟利用小鼠肠癌模型、体外细胞实验以及人体肠道类器官模型验证KRAS G12D引起Fn定植并相互作用；利用荧光原位杂交实验（FISH）、液相色谱-质谱联用技术（LC/MS）和免疫共沉淀实验（Co-IP）明确Fn与KRAS G12D肠上皮细胞互作方式、作用位点及所涉及的分子机制，并通过特异抗体的制备探索靶向Fn特异结合蛋白能否成为干预KRAS突变大肠癌患者的新手段。本项目是在前期研究基础上提出的新探索，不仅有助于推动肠道核心致病菌Fn相关基础研究成果向临床应用转化，更推进CRC个体化精准治疗体系。

It remains unclear that whether fusobacterium nucleatum (Fn) as the core pathogenic bacteria could induce cell carcinogenesis depending on different molecular characteristics. Our previous data show that Fn abundance was significantly increased in cancer tissues of patients with KRAS mutations and was more susceptible to KRAS G12D mutation site. Therefore, we successfully constructed Kras LSL-G12D/Vilin-Cre mouse model which selectively activated KRAS in intestinal epithelial cells. Next, we will verify that KRAS G12D mutation causes Fn colonization and then Fn could interact with KRAS G12D cancerous cells by mouse model, in vitro experiments and human intestinal organoid model. Furthermore, we will clarify the molecular mechanisms by fluorescence in situ hybridization (FISH), liquid chromatography-mass spectrometry (LC/MS) and co-immunoprecipitation (Co-IP) and explore whether targeting Fn-specific binding protein could become a new way for the treatment of CRC patients with KRAS G12D mutation. This project is a new exploration based on the previous research and not only helps to promote the translation of the basic research of Fn to the clinical application, but also promotes the development of the CRC individualized precision treatment system.