Abstract：
The correlation of imbalanced gut microbiota with the onset and progression of colorectal cancer (CRC) has become clear. This work investigates the effect of metformin on gut microbiota and genesis of CRC in mice. Human fecal samples were collected from healthy control (HC) donors and CRC patients. Compared to HC donors, CRC patients had reduced abundance of gut microbiota; however, they had increased abundance of detrimental Bacteroidetes. Mice were injected with azomethane (AOM) to induce colorectal tumorigenesis models. Treatment of CRC patients-sourced fecal microbiota promoted tumorigenesis, and it increased the expression of Ki67, β-catenin, COX-2, and Cyclin D1 in mouse colon tissues. Further treatment of metformin blocked the colorectal tumorigenesis in mice. Fecal microbiota from the metformin-treated mice was collected, which showed decreased Bacteroidetes abundance and suppressed AOM-induced colorectal tumorigenesis in mice as well. Moreover, the metformin- modified microbiota promoted the M1 macrophage-related markers IL-6 and iNOS but suppressed the M2 macrophage-related markers IL-4R and Arg1 in mouse colon tissues. In conclusion, this study suggests that metformin-mediated gut microbiota alteration suppresses macrophage M2 polarization to block colorectal tumorigenesis.
摘要：
肠道菌群失衡与结直肠癌（CRC）发生和发展的相关性已变得清晰。这项工作研究了二甲双胍对小鼠肠道菌群和CRC发生的影响。从健康对照(HC)供体和CRC患者收集人粪便样品。与HC捐赠者相比，CRC患者的肠道菌群丰度降低；然而，他们增加了大量有害的拟杆菌。小鼠注射偶氮甲烷(AOM)以诱导结肠直肠肿瘤发生模型。治疗CRC患者来源的粪便菌群促进肿瘤发生，它增加了Ki67，β-catenin的表达，小鼠结肠组织中的COX-2和CyclinD1。二甲双胍的进一步治疗阻断小鼠结肠直肠肿瘤发生。收集二甲双胍治疗小鼠的粪便微生物群，它显示了减少的拟杆菌丰度，并抑制了AOM诱导的小鼠结直肠肿瘤发生。此外，二甲双胍修饰的微生物群促进小鼠结肠组织中M1巨噬细胞相关标志物IL-6和iNOS,但抑制M2巨噬细胞相关标志物IL-4R和Arg1。总之,本研究提示二甲双胍介导的肠道菌群改变抑制巨噬细胞M2极化,从而阻断结直肠肿瘤发生.
