结直肠癌(CRC)的发生发展受遗传因素和包括肠道菌群在内的环境因素之共同影响，其 中肠菌与黏膜免疫存在密切关系。具核梭杆菌(FN)是主要的参与结直肠癌发生发展的肠菌，我们曾发现其通过结合CRC细胞的TLR4并经表观遗传修饰改变和激活自噬而引起术后耐药与复发(Cell,2017)。具核梭杆菌可影响肠黏膜免疫功能，如分泌黏附因子Fap2产生免疫逃逸等。我们的预试验显示CRC癌灶cGAS通路蛋白低表达，具核梭杆菌抑制cGAS通路活性且部分依赖 其下调m6A-mRNA甲基化的作用。有理由假设具核梭杆菌通过调控mRNA的m6A修饰而影响cGAS免 疫通路进而参与CRC发生发展。但其详细机制和免疫应答调控细节等科学问题均值得深究。为此，我们将在体内外实验和临床标本进行免疫学、表观遗传和分子微生物学研究，以阐释CRC发生发展中肠菌等环境因素与宿主免疫和表观遗传修饰的网络关系。

The occurrence and development of colorectal cancer (CRC) is affected by both genetic and environmental factors including intestinal flora, in which there is a network relationship between intestinal bacteria and mucosal immunity. Fusobacterium nucleatum (FN) is the most important factor involved in the occurrence and development of colorectal cancer. We both have found that they can bind to the TLR4 of CRC cells and cause postoperative drug-resistance or relapse through epigenetic modulation and autophagic activation (Cell, 2017). FN may also affect intestinal mucosal immune function, such as the secretion of adhesion factor Fap2 to cause immune escape. Our preliminary experiments showed that FN reduced the activity of the cGAS pathway, which was partially dependent on the downregulation of m6A-mRNA methylation level. Therefore, it is reasonable to assume that FN is involved in the development of colorectal cancer by regulating the m6A modification of mRNA and affecting the cGAS immune pathway. However, scientific issues such as detailed mechanisms and regulatory details are worthy of further investigation. To this end, we will further clarify the network relationship among the environmental factors such as intestinal bacteria, host immunity and epigenetic modification.