Department of Gastrointestinal Surgery, The First Affiliated Hospital of Gannan Medical College, Ganzhou, 341000, Jiangxi, People's Republic of China.
Department of Gastroenterology, The First Affiliated Hospital of Gannan Medical College, Ganzhou, 341000, Jiangxi, People's Republic of China.
J Microbiol. 2023 Jan;61(1):109-120. doi: 10.1007/s12275-022-00010-8. Epub 2023 Jan 26.
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.
肠道微生物群落失衡与结直肠癌（CRC）的发生和发展密切相关。本研究旨在探讨二甲双胍对小鼠肠道微生物群落和CRC 发生的影响。收集健康对照（HC）供体和 CRC 患者的人粪便样本。与 HC 供体相比，CRC 患者的肠道微生物群落丰度降低，但有害的拟杆菌丰度增加。通过注射偶氮甲烷（AOM）诱导小鼠结直肠肿瘤发生模型。CRC 患者来源的粪便微生物群促进肿瘤发生，并增加了小鼠结肠组织中 Ki67、β-连环蛋白、COX-2 和细胞周期蛋白 D1 的表达。进一步用二甲双胍治疗可阻断小鼠的结直肠肿瘤发生。收集二甲双胍治疗小鼠的粪便微生物群，发现其拟杆菌丰度降低，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了 M1 巨噬细胞相关标志物 IL-6 和 iNOS，但抑制了 M2 巨噬细胞相关标志物 IL-4R 和 Arg1 在小鼠结肠组织中的表达。综上所述，本研究表明，二甲双胍介导的肠道微生物群改变抑制巨噬细胞 M2 极化，从而阻断结直肠肿瘤的发生。
