结肠癌的发生受遗传因素与环境因素共同影响，后者主要包括肠道菌群与肠黏膜免疫组成的肠道微环境。然而，肠道微环境稳态调控在炎症相关结肠癌（CAC）发生中的作用及机制并不清楚。既往研究表明，宿主基因可通过改变肠道菌群结构而参与肠道微环境稳态的调控。我们前期发现，TRPV4可促进结肠炎症而致肠道菌群结构改变进而促进CAC发生，而巨噬细胞及IL-23/IL-17A信号可能在其中发挥重要作用。据此推测TRPV4可促进炎症反应调控抗菌肽表达而致菌群结构改变，而TRPV4介导的菌群结构可激活巨噬细胞表达IL-23进而通过IL-23/IL-17A信号促进肠上皮无限增殖及恶性转化，最终导致CAC的发生。本研究拟通过基因敲除、无菌动物模型、16S扩增子测序、Cohousing及粪菌移植（FMT）等阐明肠道菌群参与介导TRPV4促CAC发生的作用及机制，为结肠癌的防治提供新的靶点及理论依据。

Genetic and environmental factors are responsible for the pathogenesis of colon cancer, while the intestinal microenvironment comprised of gut microbiota and mucosal immune system is a key component of the environmental factors. However, the function and mechanism of microenvironment dysbiosis in pathogenesis of colitis-associated colon cancer (CAC) remain unclear. Previous research showed that the host genes could regulate the homeostasis of intestinal microenvironment through shaping the microbiota. Our previous results showed that TRPV4 could shape the gut microbiota by promoting the colitis to promote the carcinogenesis of CAC, in which the macrophages and IL-23/IL-17A signaling may play an important role. Based on the previous studies and our results, we speculate that TRPV4 could shape the gut microbiota by promoting the inflammation and regulating the antimicrobial peptides expression, and the TRPV4-mediated microbiota could activate the macrophages to express IL-23, and further promote the intestinal epithelium cells uncontrolled proliferation and transformation through IL-23/IL-17A signaling and carcinogenesis of CAC. Our study will apply the knockout mice, germ-free mice, 16S sequencing, cohousing and fecal microbiota transplantation to illustrate the function and mechanism of gut microbiota in TRPV4-induced pathogenesis of CAC, and to provide novel target and evidence for prevention and treatment of colon cancer.