Title |
Metformin Regulates Gut Microbiota Abundance to Suppress M2 Skewing of Macrophages and Colorectal Tumorigenesis in Mice |
Author |
Linfeng Fan1, Xiangfu Zeng1, and Guofeng Xu2* |
Address |
1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Gannan Medical College, Ganzhou 341000, Jiangxi, People’s Republic of China, 2Department of Gastroenterology, The First Affiliated Hospital of Gannan Medical College, Ganzhou 341000, Jiangxi, People’s Republic of China |
Bibliography |
Journal of Microbiology, 61(1),109-120, 2023,
|
DOI |
10.1007/s12275-022-00010-8
|
Key Words |
Gut microbiota · Metformin · Microbiota transplantation · Colorectal cancer · Macrophage polarization |
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. |