Lu Haiyang, Xu Xiaoqiang, Fu Di, Gu Yubei, Fan Rong, Yi Hongmei, He Xiangyi, Wang Chaofu, Ouyang Binshen, Zhao Ping, Wang Li, Xu Pengpeng, Cheng Shu, Wang Zhifeng, Zou Duowu, Han Lizhong, Zhao Weili
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Laboratory of Molecular Pathology, Shanghai 200025, China.
Department of Bioinformatics, 01life Institute, Shenzhen 518000, Guangdong, China.
Cell Host Microbe. 2022 Aug 10;30(8):1139-1150.e7. doi: 10.1016/j.chom.2022.07.003.
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已得到充分证实，但在血液系统恶性肿瘤中很少被研究。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独特的微生物群特征，共生微生物显著减少，尤其是真杆菌属，特别是产丁酸的直肠真杆菌。将肠道淋巴瘤患者的直肠真杆菌缺陷微生物群转移到小鼠体内会导致炎症和肿瘤坏死因子（TNF）产生。相反，直肠真杆菌治疗降低了致敏Eμ-Myc小鼠的TNF水平和淋巴瘤发病率。此外，淋巴瘤患者和小鼠常驻微生物群中的脂多糖与TNF信号协同作用，并通过依赖MyD88的TLR4信号增强NF-κB途径，共同促进肠道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以及针对肠道微生物群进行治疗的潜在临床依据。
