肠道微生物调节昼夜节律诱导结直肠癌发生、发展的机制研究

近年来，随着社会生活节奏加快、饮食结构变化和生活作息不规律，结直肠癌发病率逐年升高。研究表明多种肠道微生物参与结直肠癌的发生、发展；昼夜节律紊乱促进结直肠癌病程进展，降低了治疗效果；结直肠组织的昼夜节律受到肠道微生物及其代谢产物调节。我们的前期工作证明肠道粘膜定植微生物具有时间和空间异质性；小分子化合物对结直肠癌细胞增殖的抑制作用呈现昼夜节律规律；而且，体内试验还验证了大肠杆菌抑制结肠组织昼夜节律钟蛋白PER1和PER2的表达。因此，我们认为肠道菌群失调引起的昼夜节律紊乱可能参与结直肠癌的发生、发展。我们拟研究肠道菌群失调和昼夜节律紊乱与结直肠癌患者生存率之间的关联，以及相关分子机制。研究工作将有助于阐明结直肠癌患者肠道微生物与宿主昼夜节律互作机制，为肠道微生态联合昼夜节律治疗结直肠癌提供理论基础。

In recent years, colorectal cancer incidence keeps increasing along with rapid living pace, change of diet habit and irregular work routine. Studies reported that intestinal microbes were involved in colorectal carcinoma initiation and development; circadian rhythm disorder aggravated colorectal carcinoma course, decreased therapeutic effects. bacteria and their metabolites orchestrated intestinal transcription; Our previous works indicate that bacterial inhabiting on intestinal mucosa showed a time and location heterogeneity；small molecular compound-decreased inhibitions of colorectal cancer cell proliferation were related to circadian rhythm; further, Escherichia coli insulting depressed expressions of circadian clock proteins PER1 and PER2 in mouse colon tissue. Therefore, we hypothesized that circadian rhythm disorder-induced intestinal microbiota dysbiosis boosts colorectal carcinogenesis and development. Our next works will focus on the connection of circadian rhythm disorder-induced intestinal microbiota dysbiosis with survival of colorectal cancer patients, and related mechanism. Our foci are expected to clear the circadian mutual action between intestinal microbes and host, provide basic supports for colorectal carcinoma therapeutic via combining intestinal microbes and circadian rhythm.