大肠癌(colorectal cancer)是常见的恶性肿瘤之一，膳食结构的变化、高脂食物比重增加与大肠癌发病率增高密切相关，但其中机制尚不明确。我们基于前期对大肠癌特征性代谢模式、大肠癌相关miRNA调控网络及益生菌对肠癌干预效果的研究为基础，提出膳食结构的改变可能通过影响肠道微生态及代谢模式，引起结肠上皮细胞内miRNA调控网络的变化，进而通过下游相关信号通路导致大肠癌的发生发展。为此，我们率先利用高通量测序技术及代谢组学方法筛选二个社区人群肠道中共生菌群谱的差异、找出特征性致癌菌；同时分析高脂饮食及其代谢产物、肠道菌群严重失衡与肠癌发生的关联性；通过细胞及动物模型实验进一步阐明miRNA及相关信号通路在其中发挥的重要作用。同时，在上述地区观察优化肠道微生态平衡对大肠癌发病风险的影响，为添加微生态制剂以调整肠道菌群、降低致癌性菌株的丰度，从而降低肠癌发病提供理论基础和实践依据。

Colorectal cancer is a common malignancy, and the changes of dietary structure, the increase in the proportion of high-fat foods is related to the incidence of colorectal cancer, although the mechanism is not yet clear. On the basis of our previous research of colorectal characteristic metabolic, miRNA related regulation network and probiotic intervention in colorectal cancer (CRC), we hypothesized that dietary changes in the structure may affect the gut microflora and metabolism, causing changes in the miRNA regulatory network in the colonic epithelial cells, and then lead to the development of colorectal carcinoma through the downstream signaling pathways. To test this hypothesis, we take the lead in screening different intestinal symbiotic microflora spectrum, the metabolism of food spectrum and its regular change in between the people of two communities with different diet and finding carcinogenic bacterium using high-throughput sequencing technology and metabolomics approach, explore the pathway of diet- intestinal flora- metabolites-miRNA regulatory network-tumor, to study the the influence of high fat - intestinal microecology - miRNA related signaling pathways on the occurrence and development of CRC in cell, animal and human specimens levels; and further to elucidate the effect of the optimization of dietary structure and the maintence of intestinal microecological balance on the CRC risk in the two communities mentioned above. This research will provide important theoretical foundation and practice basis for clearifing the intestinal flora and the metabolism model of high risk population, and exploring the reduction of CRC incidence through adjusting diet structure and reducing the abundance of carcinogenic bacterium.