Microbiota-induced tumorigenesis is well established in solid tumors of the gastrointestinal tract but rarely explored in hematologic malignancies. To determine the role of gut microbiota in lymphoma progression, we performed metagenomic sequencing on human primary gastrointestinal B cell lymphomas. We identified a distinct microbiota profile of intestinal lymphoma, with significantly decreased symbiotic microbes, particularly the genus Eubacterium and notably butyrate-producing Eubacterium rectale. Transfer of E. rectale-deficit microbiota of intestinal lymphoma patients to mice caused inflammation and tumor necrosis factor (TNF) production. Conversely, E. rectale treatment reduced TNF levels and the incidence of lymphoma in sensitized Eμ-Myc mice. Moreover, lipopolysaccharide from the resident microbiota of lymphoma patients and mice synergizes with TNF signaling and reinforces the NF-κB pathway via the MyD88-dependent TLR4 signaling, amalgamating in enhanced intestinal B cell survival and proliferation. These findings reveal a mechanism of inflammation-associated lymphomagenesis and a potential clinical rationale for therapeutic targeting of gut microbiota.

微生物群诱导的肿瘤发生在胃肠道实体瘤中得到了很好的证实，但很少在血液系统恶性肿瘤中进行探索。为了确定肠道微生物群在淋巴瘤进展中的作用，我们对人类原发性胃肠道 B 细胞淋巴瘤进行了宏基因组测序。我们确定了肠道淋巴瘤的独特微生物群谱，共生微生物显着减少，特别是真杆菌属，尤其是产丁酸盐的直肠真杆菌。将肠淋巴瘤患者的直肠大肠杆菌缺陷微生物群转移到小鼠体内会引起炎症和肿瘤坏死因子 (TNF) 的产生。相反，E. rectale治疗降低了致敏的 Eμ-Myc小鼠的 TNF 水平和淋巴瘤的发病率。此外，来自淋巴瘤患者和小鼠的常驻微生物群的脂多糖与 TNF 信号通路协同作用，并通过 MyD88 依赖性 TLR4 信号通路增强 NF-κB 通路，从而增强肠道 B 细胞的存活和增殖。这些发现揭示了炎症相关淋巴瘤发生的机制和肠道微生物群治疗靶向的潜在临床原理。