梭杆菌感染在结肠癌发生发展中的作用及机制初步研究

Although it is definite that the relevant abundance of Fusobacterium is increased in colorectal mucosa of colorectal cancer (CRC) patients, and also Fusobacterium can invade intestinal tissue and lead to the inflammatory response of the host, whether the association between Fusobacterium and CRC is involved in colon carcinoma pathology, or simply the result of Fusobacterium exploitation of an ecological niche created as a result of the cancer tumor microenvironment, remains to be tested. This project uses molecular biology and histotomy methods in mice model of CRC to reveal the answer of this question through dynamic observation of CRC development and progression. Meanwhile, based on "Alpha-Bug" hypothesis-certain microbiome members that possessing unique virulence traits, such as enterotoxigenic Bacteroides fragilis, are not only directly pro-oncogenic but are capable of remodeling the microbiome as a whole, thus promoting mucosal immune responses and colonic epithelial cell changes and resulting in colon cancer, we try to preliminarily reveal why bacteria could induce disease iniation or development through detection of intestinal epithelial hyperplasia, inflammation, DNA injury, especially structure changes of intestine lumial microbiota respectively. This research will be demonstration of relationship between CRC development (or progression) and bacterial infections. And the result will be facilitated to the prevention and effective treatment of CRC.

梭杆菌在结直肠癌患者粘膜中大量增加及其能入侵肠道导致宿主炎症反应的事实，已在申请人前期工作以及其他多份研究报告中得到了确认，但究竟是因为梭杆菌的感染促进了结直肠癌的发生发展，还是仅仅是结直肠癌的发生导致了梭杆菌的大量增殖，这个问题还没有答案。本项目利用分子生物学方法和组织切片技术等手段，通过对梭杆菌预感染的AOM诱导小鼠的动态观察研究，来探讨其是否能促进直肠癌的发生或发展。同时，依据细菌致癌的Alpha-bug假说- - "特定细菌不仅本身能作为一种致癌的因素，引起宿主炎症反应、DNA损伤和上皮细胞病变，而且还能改变微生物菌群的结构，并使之作为一个整体进一步促进宿主炎症反应，引起上皮细胞恶性增殖，最终导致癌症发生"，我们从肠道上皮增生、炎症、DNA损伤，特别是从肠道菌群结构变化的角度，来初步探讨梭杆菌的致病机制。本研究将初步探讨细菌感染对结直肠癌发生发展的影响，对直肠癌的病因学研究有重要意义。