Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Shahid Arabi Ave., Yemen St, Velenjak, Tehran, Iran.
Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mol Biol Rep. 2024 Feb 1;51(1):265. doi: 10.1007/s11033-024-09273-3.
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.
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.
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.
肠道微生物群已成为结直肠癌（CRC）形成和发展的主要危险因素之一。CRC 的恶化可能是由于微生物病原体的定植及其释放的代谢物。在这里，我们分析了 CRC 患者的拟杆菌门和梭菌细菌，并研究了癌组织与相邻正常组织中的细菌代谢组。
通过 RT-qPCR 研究了 30 名 CRC 患者活检标本中选定细菌的种群。通过 Ames 试验和 MTT 分析分别评估了微生物群代谢物的致突变性和细胞毒性作用。此外，通过 RT-qPCR 研究了致癌途径中的基因表达，并诊断了肿瘤组织和非肿瘤组织中差异表达的基因。基于微生物组分析，CRC 组织中梭菌和艰难梭菌的相对丰度明显更高，而产气荚膜梭菌在正常组织中的相对丰度更高。AIMES 试验证实了 CRC 患者中细菌代谢物的增殖和致突变作用。与对照组相比，CRC 样本中 C-Myc、GRB2、IL-8、EGFR、PI3K 和 AKT 的表达显著上调，而 ATM 的表达下调。
观察到细菌代谢物对炎症和细胞信号通路中基因表达的改变的影响。这些发现证实了肠道微生物群组成和细菌代谢物作为 CRC 发生和发展的关键因素的作用。
