牙龈卟啉单胞菌通过NLRPs炎症小体途径促进结肠上皮细胞恶性转化的机制研究

口腔微生物与消化道肿瘤具有较强的相关性，但前者在肿瘤发生中的演替规律、因果关系及互作机制未能得到深入阐释。本课题组预实验结果显示高糖饮食小鼠粪便中检测到牙龈卟啉单胞菌（Pg）数量增多，而Pg肠道感染模型可诱发结肠癌，该癌变组织微环境中检测到炎症小体NLRPs相关炎性分子表达变化。由此，本研究假设：Pg增多引起的肠道微生态失衡可通过NLRPs炎症小体途径促进结肠上皮恶性转化，且Pg自发诱癌可受全身系统糖代谢影响。本项目以消化道肿瘤中炎癌转换最典型的结肠癌为模型，同时关注肠上皮细胞和黏膜下免疫细胞内炎症小体介导的的分子机制，多层次地研究口腔微生物诱发的肠道微生态失衡与炎癌转化的的调控机制。同时利用元基因组技术探索全身糖代谢因素对此过程的影响，以期为后续代谢互作机制提供理论基础，最终拟为开拓针对营养代谢感应和微生态平衡的全身性重大疾病的临床转化策略提供新思路。

Oral microbiome has a tight association with gastrointestinal cancer, but its causal relationship and interaction mechanism are failed to be described in great depth. The researchers have found the presence of Porphyromonas gingivalis(Pg) correlated with colon cancer. Our preliminary experiments showed that Pg detected in the feces of high-sugar diet mice has a relatively high abundance. Moreover, we also established the colon cancer induced by Pg-intestinal infection model, where the expression changes of NLRPs complex related inflammatory molecules can be detected in the tissue microenvironment. Thus, this research hypothesis: intestinal microflora disorders (mainly increased by Pg) could promote colon cancer growth and metastasis through NLRPs inflammation complex pathways, Pg spontaneously induced tumorigenesis can be affected by systemic glucose metabolism. This project adopts the most typical inflammatory carcinoma transformation model of colon cancer, focusing on the molecular mechanisms mediated by inflammation complex both in intestinal epithelial cells and mucosal immune cells, and the regulation mechanism through multi-level study of oral microbial induced intestinal flora imbalance and inflammatory carcinoma transformation. Meanwhile, we use metagenomics analysis to explore the influence of this progress based on the whole body metabolic factors, providing a theoretical basis for the interaction mechanisms of subsequent metabolism. Ultimately, we intended to propose the new ideas for systemic diseases associated clinical transformation strategy by exploring the nutritional metabolism induction and micro-ecology balance.