Han Xing, Zhang Bo-Wen, Zeng Wei, Ma Meng-Lin, Wang Ke-Xin, Yuan Bao-Juan, Xu Dan-Qi, Geng Jia-Xin, Fan Chao-Yuan, Gao Zhan-Kui, Arshad Muhammad, Gao Shan, Zhao Liangliang, Liu Shu-Lin, Mu Xiao-Qin
Genomics Research Center (Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province), College of Pharmacy, Harbin Medical University, Harbin, China.
National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin Medical University, Harbin, China.
Front Microbiol. 2024 Nov 13;15:1451303. doi: 10.3389/fmicb.2024.1451303. eCollection 2024.
Dysbiosis of the intestinal microbiota is prevalent among patients with colorectal cancer (CRC). This study aims to explore the anticancer roles of the fecal microbiota in inhibiting the progression of colorectal cancer and possible mechanisms. The intestinal microbial dysbiosis in CRC mice was significantly ameliorated by fecal microbiota transplantation (FMT), as indicated by the restored ACE index and Shannon index. The diameter and number of cancerous foci were significantly decreased in CRC mice treated with FMT, along with the restoration of the intestinal mucosal structure and the lessening of the gland arrangement disorder. Key factors in oxidative stress (TXN1, TXNRD1, and HIF-1α); cell cycle regulators (IGF-1, BIRC5, CDK8, HDAC2, EGFR, and CTSL); and a critical transcription factor of the innate immune signal pathway (IRF5) were among the repressed oncogenic targets engaged in the FMT treatment of CRC. Correlation analysis revealed that their expressions were positively correlated with uncultured_bacterium_o_Mollicutes_RF39, Rikenellaceae_RC9_gut_group, and negatively correlated with , , , , , , , and genera of uncultured_bacterium_f_Eggerthellaceae, uncultured_bacterium_f_Xanthobacteraceae, Prevotellaceae_UCG-001, uncultured_bacterium_f_Erysipelotrichaceae, uncul-tured_bacterium_f_Lachnospiraceae, uncultured_bacterium_f_Ruminococcaceae, Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-005, and uncultured_bacterium_f_Peptococcaceae. This study provides more evidence for the application of FMT in the clinical treatment of CRC.
肠道微生物群失调在结直肠癌（CRC）患者中普遍存在。本研究旨在探讨粪便微生物群在抑制结直肠癌进展中的抗癌作用及可能机制。粪便微生物群移植（FMT）显著改善了CRC小鼠的肠道微生物失调，ACE指数和香农指数的恢复表明了这一点。FMT治疗的CRC小鼠癌灶直径和数量显著减少，同时肠道黏膜结构得以恢复，腺体排列紊乱减轻。氧化应激的关键因子（TXN1、TXNRD1和HIF-1α）；细胞周期调节因子（IGF-1、BIRC5、CDK8、HDAC2、EGFR和CTSL）；以及先天免疫信号通路的关键转录因子（IRF5）是FMT治疗CRC所涉及的受抑制致癌靶点。相关性分析显示，它们的表达与未培养细菌_o_柔膜菌纲_RF39、理研菌科_RC9肠道菌群呈正相关，与未培养细菌_f_埃格特菌科、未培养细菌_f_黄杆菌科、普雷沃氏菌科_UCG-001、未培养细菌_f_丹毒丝菌科、未培养细菌_f_毛螺菌科、未培养细菌_f_瘤胃球菌科、真杆菌属产粪甾醇菌群、瘤胃球菌科_UCG-005和未培养细菌_f_消化球菌科的属呈负相关。本研究为FMT在CRC临床治疗中的应用提供了更多证据。
