Eubacterium limosum modulates tumor microenvironments and produces antitumor metabolites active against colorectal cancer

作者：Yao Lu, Ruiting Lan, Qianhua Fan, Huijing Tang, Dalong Hu, Shuwei Zhang, Xiaoying Lin, Ruoshi Wang, R. Zhao, Hui Sun, Liyun Liu, Jianguo Xu · 发表于：The ISME Journal · 年份：2025 · DOI：10.1093/ismejo/wraf130 · 被引用次数：5 · 研究领域：Cancer Research and Treatments、Probiotics and Fermented Foods、Gut microbiota and health

Gut microbiota play a key role in ameliorating colorectal cancer (CRC). Eubacterium limosum is a potential probiotic with anti-CRC functions. However, the mechanistic basis of its anti-CRC effect remains largely unknown. In vitro, we detected the effects of the E. limosum strain El1405 on cell proliferation, colony formation, cell cycle, and apoptosis of CRC cells, and found that El1405CS specifically suppressed cell proliferation by altering cell cycle distribution and inducing apoptosis. In the CT26 syngeneic mouse model, daily gavage with live El1405, inactivated El1405, culture supernatant of El1405, and El1405-derived indole derivatives, including indole-3-lactic acid (ILA), indole-3-acetic acid (IAA), L-arginine, and butyrate, inhibited tumor growth. Analysis of the 16S rRNA gene sequences revealed that El1405 altered the microbiota compositions within tumors, primarily reducing the abundance of Enterobacter, Pseudomonas, and Staphylococcus. Staphylococcus succinus isolated from the tumors of CT26 syngeneic mice promoted abdominal metastasis of tumors. Moreover, El1405 intervention significantly increased the levels of TNF-α, INF-γ, and CD8 in the tumor microenvironment, while decreasing the levels of CD4, IL-6, IL-10, and TGF-β. Metabolomic analysis indicated that El1405 induced antitumor effects through changing the serum metabolome of mice by producing indole derivatives such as ILA and IAA. Furthermore, 16S rRNA gene sequencing demonstrated that El1405 intervention ...