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Alterations in the Gut Microbiota and Their Metabolites in Human Intestinal Epithelial Cells of Patients With Colorectal Cancer Publisher Pubmed



Jahanisherafat S1, 2, 3 ; Azimirad M1 ; Raeisi H1 ; Azizmohammad Looha M4 ; Tavakkoli S4 ; Ahmadi Amoli H5 ; Moghim S3 ; Rostaminejad M4, 6, 7 ; Yadegar A1 ; Zali MR4
Authors
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Authors Affiliations
  1. 1. Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Shahid Arabi Ave., Yemen St, Tehran, Velenjak, Iran
  2. 2. Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  3. 3. Microbiology Department, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  7. 7. Celiac Disease and Gluten Related Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Source: Molecular Biology Reports Published:2024


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. © 2024, The Author(s), under exclusive licence to Springer Nature B.V.
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