Gut commensal bacteria influence colorectal cancer development by modulating immune response in AOM/DSS-treated mice

作者：Danlei Zhou, Yujing Sun, Peipei Ding, Xiaochao Wang, Ling Li, Luying Li, Xinyue Lv, Tian Liao, Jianfeng Chen, Wei Zhang, Qi Wang, Qinghai Ji, Feng Gao, Weiguo Hu · 发表于：Microbiology Spectrum · 年份：2025 · DOI：10.1128/spectrum.02792-24 · 被引用次数：6 · 研究领域：Gut microbiota and health、Clostridium difficile and Clostridium perfringens research、Probiotics and Fermented Foods

ABSTRACT The gut microbiota has been closely associated with the pathogenesis of colorectal cancer (CRC). However, precise identification of particular microorganisms promoting CRC carcinogenesis, and more importantly those blocking tumor development, has been challenging based on human gut microbiota profiling studies. With a well-established azoxymethane/dextran sodium sulfate induction murine CRC model, we found a subset of mice consistently failed to develop CRC. This genetically homogeneous but cancer-refractory population gave us a unique opportunity to reveal that the microbial compositions between mice with and without CRC formation are indeed distinct, indicating key different gut microbiota between those groups are responsible for the differential susceptibility of the animals to CRC development. Our analysis revealed that Ruminococcus flavefaciens (R.f) and Fibrobacter succinogenes (F.s) were significantly enriched in CRC-free mice, while the presence of Eubacterium dolichum (E.d) was dramatically reduced. The correlative evidence was further substantiated as important causal factors, with subsequent bacteria intragastric administration experiments demonstrating independent, protective roles of R.f and F.s and a correspondingly detrimental role of E.d in inflammation-induced CRC initiation. Notably, E.d strongly activates NF-κB and promotes the local accumulation of myeloid-derived suppressor cells and macrophages. Significant disturbance of gut immune homeostasis,...