肠道菌群在结直肠癌(CRC)化疗中起重要作用。改善CRC化疗敏感相关细菌及其作用机制尚未明确。以益生菌Sb干预肠道炎症及CRC小鼠肠道菌群，小鼠肠道炎症缓解、肠道肿瘤及新生血管减少，肠壁KC(IL8)表达降低。IL8与CRC化疗敏感性、复发相关，阻断TLR9可降低IL8表达。同时，p-MKK4与CRC预后及铂类化疗敏感相关。我们猜测相关细菌可能通过TLRs信号通路、作用于p-MKK4或CRC耐药基因并改善肠道炎症、肠壁血管发生、降低肿瘤代谢从而改善CRC化疗敏感性。本研究拟1）对CRC化疗敏感及耐药患者粪菌16SrRNA基因高通量测序，分析肠道菌群丰度改变与CRC化疗敏感相关性，明确改善CRC化疗敏感相关菌株；2)明确相关细菌是否通过TLRs信号通路、p-MKK4与CRC耐药基因改善CRC化疗敏感性；3)明确相关细菌是否通过缓解肠道炎症、血管发生及肿瘤代谢改善CRC化疗敏感性。

Gut microbiota play important roles in the chemotherapy of colorectal cancer (CRC). The molecular mechanisms by which bacterial metabolite might improves chemotherapy efficiency are still not clear. Probiotics Sb treatment can attenuate intestinal inflammation, angiogenesis and tumorigenesis significantly in colitis and CRC mice model. IL8/KC is an important inflammatory cytokine which can stimulate angiogenesis. IL8 was found had a strong relation with CRC chemotherapy and prognosis. Blockage of TLR9 would induce significant reduction of IL8. Meanwhile, we found that p-MKK4 had a strong relation with prognosis and Platin-sensitivity of CRC. We suppose that the certain bacteria which might improve the chemosensitivity of CRC through TLRs signaling pathways, influence of p-MKK4 and chemoresistant genes or remission of intestinal inflammation, angiogenesis and tumor metabolism. In the present study, we are going to identify the chemosensitivity-promoting bacteria species in the gut microbiota from chemosensitive CRC patients by 16S rRNA gene sequencing and to character the working mechanisms of TLRs signaling pathway, p-MKK4 and chemoresistant genes and intestinal inflammation and angiogenesis and tumor metabolism in the bacteria mediated chemosensitivity promotion. The results of this study can provide valuable information for gut microbiota targeted individual therapy to improve the chemosensitivity or the antagonism of chemoresistance in CRC patients.