Background: EnterotoxigenicBacteroides fragilis(ETBF) carries thebfttoxin gene, which influences the host immune response and inflammatory pathways and promotes colorectal cancer (CRC). This study investigated the potential role of ETBF in CRC liver metastasis.Methods: We reviewed the records of 226 consecutive patients who underwent curative-intent (R0) resection of CRC liver metastases. ETBF DNA in fresh-frozen metastasis specimens was quantified using droplet digital PCR (ddPCR). Patients were grouped into very-low (≤80%;N= 178), low (80–90%;N= 24), and high (>90%;N= 24) ETBF-DNA groups. Three tissue cores per specimen were stained for CD8, CD4, CD20, FOXP3, CD68, and CD163, and immune-cell densities were measured digitally (cells/mm2).Results: ETBF DNA was detected in 219 of 226 lesions (96.9%). The densities of cytotoxic CD8+T-cells, effector CD4+T-cells, CD20+B-cells, and CD163+macrophages did not differ significantly by ETBF-DNA group (Ptrendall > 0.12). FOXP3+regulatory T-cells (Tregs) decreased (Ptrend= 0.010), and CD68+macrophages increased (Ptrend= 0.020) as ETBF-DNA levels increased. ETBF-DNA levels in CRC liver metastases were not associated with disease-free survival or overall survival or serum C-reactive protein levels.Conclusions: ETBF was present in almost all CRC liver metastases. Higher ETBF levels were associated with a tumor-immune microenvironment enriched in CD68+macrophages and deficient in FOXP3+Tregs, suggesting that ETBF facilitates immune evasion without loss of effector lymphocytes. Although ETBF-DNA levels did not predict survival in this single-center cohort, the potential role of ETBF in immune remodeling and as a candidate biomarker and therapeutic target in metastatic CRC warrants further study.
背景：产肠毒素脆弱拟杆菌（ETBF）携带bft毒素基因，该基因可影响宿主免疫应答与炎症通路，并促进结直肠癌（CRC）发生。本研究旨在探讨ETBF在CRC肝转移中的潜在作用。 方法：回顾性分析连续226例接受根治性（R0）切除的CRC肝转移患者资料。采用微滴式数字PCR（ddPCR）技术对新鲜冷冻转移灶标本中的ETBF DNA进行定量检测。根据ETBF-DNA水平将患者分为极低组（≤80%；N=178）、低组（80-90%；N=24）和高组（>90%；N=24）。每个标本取三个组织芯，分别进行CD8、CD4、CD20、FOXP3、CD68和CD163染色，并通过数字化方法测量免疫细胞密度（细胞数/mm²）。 结果：226个病灶中219个（96.9%）检出ETBF DNA。细胞毒性CD8⁺ T细胞、效应性CD4⁺ T细胞、CD20⁺ B细胞及CD163⁺巨噬细胞的密度在各ETBF-DNA组间无显著差异（趋势检验P值均>0.12）。随着ETBF-DNA水平升高，FOXP3⁺调节性T细胞（Tregs）呈下降趋势（趋势检验P=0.010），而CD68⁺巨噬细胞呈上升趋势（趋势检验P=0.020）。CRC肝转移灶中ETBF-DNA水平与无病生存期、总生存期及血清C反应蛋白水平均无显著关联。 结论：ETBF几乎存在于所有CRC肝转移灶中。较高水平的ETBF与富含CD68⁺巨噬细胞而缺乏FOXP3⁺ Tregs的肿瘤免疫微环境相关，提示ETBF可能在效应淋巴细胞不减少的情况下促进免疫逃逸。尽管在本单中心队列中ETBF-DNA水平未能预测生存结局，但ETBF在免疫重塑中的潜在作用及其作为转移性CRC生物标志物和治疗靶点的价值值得进一步研究。
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