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- Metformin Regulates Gut Microbiota Abundance to Suppress M2 Skewing of Macrophages and Colorectal Tumorigenesis in Mice
- Linfeng Fan , Xiangfu Zeng , Guofeng Xu
- J. Microbiol. 2023;61(1):109-120. Published online January 26, 2023
- DOI: https://doi.org/10.1007/s12275-022-00010-8
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- 5 Web of Science
- 4 Crossref
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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.
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Citations
Citations to this article as recorded by
- Metformin alleviates colitis-associated colorectal cancer via inhibition of the TLR4/MyD88/NFκB/MAPK pathway and macrophage M2 polarization
Xueying Lai, Bin Liu, Yu Wan, Ping Zhou, Wanjun Li, Wei Hu, Wei Gong
International Immunopharmacology.2025; 144: 113683. CrossRef - Metformin as an immunomodulatory agent in enhancing head and neck squamous cell carcinoma therapies
Wenting Li, Nanshu Liu, Mingwei Chen, Dongjuan Liu, Sai Liu
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2025; 1880(2): 189262. CrossRef - Clinical efficacy of metformin in familial adenomatous polyposis and the effect of intestinal flora
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Orphanet Journal of Rare Diseases.2024;[Epub] CrossRef - An AMPK agonist suppresses the progress of colorectal cancer by regulating the polarization of TAM to M1 through inhibition of HIF-1α and mTOR signal pathway
Yuanyuan Cao, Mingyi Wo, Chan Xu, Xianming Fei, Juan Jin, Zhiming Shan
Journal of Cancer Research and Therapeutics.2023; 19(6): 1560. CrossRef
- Metformin alleviates colitis-associated colorectal cancer via inhibition of the TLR4/MyD88/NFκB/MAPK pathway and macrophage M2 polarization
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