Inflammatory bowel disease caused by microbial dysbiosis is an important factor contributing to colorectal cancer (CRC) initiation. The ‘driver-passenger’ model in human gut microbial dysbiosis suggests that ‘driver’ bacteria may colonize with low relative abundance on tumor site but persistently induce chronic change in normal intestinal epithelium and initiate CRC. They are gradually replaced by ‘passenger’ bacteria later on, due to their low adaptability to the on-tumor site niche. To reveal site-specific bacterial taxon markers in CRC patients, we analyzed the gut mucosal microbiome of 75 paired samples of on-tumor and tumor-adjacent sites, 75 off-tumor sites, and 26 healthy controls. Linear discriminant analysis of relative abundance profiles revealed unique bacterial taxon distribution correlated with specific tumor sites, with Eubacterium having the distribution characteristic of potential driver bacteria. We further show that Eubacterium rectale endotoxin activates the transcription factor NF-κΒ, which regulates multiple aspects of innate and adaptive immune responses in normal colon epithelial cells. Unlike the ‘passenger’ bacterium Fusobacterium nucleatum, E. rectale promotes dextran sodium sulfate-induced colitis in Balb/c mice. Our findings reveal that E. rectale functions as a ‘driver’ bacterium and contributes to cancer initiation via promoting inflammation.

中文翻译：

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直肠真细菌通过促进结肠炎促进大肠癌的发生

由微生物营养不良引起的炎症性肠病是导致结直肠癌（CRC）发生的重要因素。人类肠道微生物功能失调的“驾驶员-乘客”模型表明，“驾驶员”细菌可能以较低的相对丰度在肿瘤部位定居，但会持续诱导正常肠上皮的慢性变化并引发CRC。由于它们对肿瘤部位利基的适应性低，后来逐渐被“客体”细菌取代。为了揭示CRC患者中特定于站点的细菌分类标记，我们分析了75个配对的肿瘤上和肿瘤相邻位点，75个非肿瘤位点以及26个健康对照的肠道粘膜微生物组。相对丰度分布的线性判别分析显示，与特定肿瘤部位相关的独特细菌分类群分布，真细菌具有潜在的驱动细菌分布特征。我们进一步显示，真细菌真核内毒素激活了转录因子NF-κΒ，后者调节正常结肠上皮细胞中先天性和适应性免疫反应的多个方面。与“客体”细菌核梭菌不同，直肠大肠杆菌在Balb / c小鼠中促进右旋糖酐硫酸钠诱导的结肠炎。我们的研究结果表明，直肠大肠杆菌作为一种“驱动程序”细菌起作用，并通过促进炎症促进癌症的发生。与“客体”细菌核梭菌不同，直肠大肠杆菌在Balb / c小鼠中促进右旋糖酐硫酸钠诱导的结肠炎。我们的研究结果表明，直肠大肠杆菌作为一种“驱动程序”细菌起作用，并通过促进炎症促进癌症的发生。与“客体”细菌核梭菌不同，直肠大肠杆菌在Balb / c小鼠中促进右旋糖酐硫酸钠诱导的结肠炎。我们的研究结果表明，直肠大肠杆菌作为一种“驱动程序”细菌起作用，并通过促进炎症促进癌症的发生。