Abstract
Background
The gut microbiota has become one of the main risk factors for the formation and development of colorectal cancer (CRC). CRC intensification may be due to the microbial pathogens’ colonization and their released metabolites. Here, we analyzed Bacteroidetes and Clostridia bacteria in CRC patients and studied bacterial metabolome in cancerous tissues compared to their adjacent normal tissues.
Methods and results
The population of selected bacteria in biopsy specimens of 30 patients with CRC was studied by RT-qPCR. The mutagenicity and cytotoxicity effects of microbiota metabolites were evaluated by Ames test and MTT Assay, respectively. Moreover, gene expression in carcinogenic pathways was studied by RT-qPCR, and genes with different expressions in tumor and non-tumor tissues were diagnosed. Based on microbiota analysis, the relative abundance of Clostridia and C. difficile was significantly higher in CRC tissue, whereas C. perfringens showed higher relative abundance in normal tissue. AIMES test confirmed the proliferation and mutagenicity effects of the bacterial metabolites in CRC patients. Significant upregulation of C-Myc, GRB2, IL-8, EGFR, PI3K, and AKT and downregulation of ATM were observed in CRC samples compared to the control.
Conclusions
The influence of bacterial metabolites on inflammation and altered expression of genes in the cell signaling pathways was observed. The findings confirm the role gut microbiota composition and bacterial metabolites as key players in CRC onset and development.
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Data availability
All relevant data are within the manuscript and its supporting information files.
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Acknowledgements
The authors wish to thank all members of the Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases and Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Funding
This study was supported financially by a grant [no. RIGLD 1090] from Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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S.J.S and M.A.: microbiological culture and experiments, molecular assays, cell culture experiments; S.J.S and M.R.N: proposal writing and project design. S.J.S, M.A, H.R. and MAL: statistical analysis, M.A, H.R. and S.T: drafting the manuscript; S.M, M.R.N and AY critical manuscript revision. M.R.Z.: clinical mentorship. All authors approved the final version of the manuscript and authorship list.
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The study was approved by Institutional Ethical Review Committee of the Research Institute for Gastroenterology and Liver Diseases at Shahid Beheshti University of Medical Sciences (IR.SBMU.RIGLD.REC.1399.011). Documented informed consent has been signed with all subjects or their legal guardians prior to sample collection. All experiments were performed in accordance with relevant guidelines and regulations.
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Jahani-Sherafat, S., Azimirad, M., Raeisi, H. et al. Alterations in the gut microbiota and their metabolites in human intestinal epithelial cells of patients with colorectal cancer. Mol Biol Rep 51, 265 (2024). https://doi.org/10.1007/s11033-024-09273-3
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DOI: https://doi.org/10.1007/s11033-024-09273-3