Streptococcus gallolyticus supernatant induces M2 macrophage polarization and activates IL-17 F signaling in colorectal tumorigenesis

作者：Jiaqi Wang, Yan Zhang, Duo Luo, Jing Xu, Xin Nie, Chen Huang, Hailan Zhao, Min‐zheng Zhu, Xue Guo, Yong Zhang, Wenjing Qiu, Haoming Xu, Yuqiang Nie, Youlian Zhou · 发表于：Gut Pathogens · 年份：2025 · DOI：10.1186/s13099-025-00731-2 · 被引用次数：5 · 研究领域：Gut microbiota and health、Oral microbiology and periodontitis research、Streptococcal Infections and Treatments

Background Colorectal cancer (CRC) is a prevalent global malignancy where gut microbiota plays a key role. Streptococcus gallolyticus (Sg), a gut commensal and opportunistic pathogen, is associated with CRC. This study investigates the impact of the supernatant derived from Sg cultures (hereafter referred to as Sgsup) on CRC progression and examines the underlying mechanisms. Methods Quantitative PCR (qPCR) was employed to assess Sg colonization in paired tumors and adjacent normal tissues from 46 CRC patients. CRC cell lines (HCT116, HT29) were treated with Sgsup, and cell proliferation was measured using the CCK-8 assay. Non-targeted metabolomic profiling of Sgsup was performed via liquid chromatography-mass spectrometry (LC-MS). An azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mouse model of CRC was used to evaluate in vivo tumor burden, inflammation, and macrophage polarization (flow cytometry). Transcriptomic analysis via RNA-seq was conducted to identify enriched signaling pathways. Results The detection rate of Sg was significantly higher in tumor tissues compared to adjacent tissues (47.8% vs. 30.4%, P < 0.01). Sgsup significantly increased CRC cell proliferation (P < 0.05). Non-targeted metabolomic analysis revealed an enrichment of metabolites, including inosine monophosphate (IMP), methionine, uridine, and creatine in Sgsup. In vivo, Sgsup increased tumor number/burden (P < 0.05), elevated inflammation scores (P < 0.05), and shortened colon length. Flow cyt...