炎症小体已被报道在造血系统恶性肿瘤的发病机制和进展中起着重要作用。作为急性淋巴细胞性白血病（ALL）的骨干药物之一，巯基嘌呤（6-MP）的抗炎作用以及6-MP引起的肠道微生物群变化对抗炎小体的影响尚不明确。我们旨在探究6-MP治疗效果与微生物介导的炎症反应之间的关联。利用静脉内注射小鼠L1210细胞于DBA/2小鼠中建立ALL小鼠模型（模型组）。细胞注射后两周，连续口服6-MP 14天（6-MP组）。在不同时间点收集小鼠的粪便样本。采用液相色谱串联质谱法测定盲肠短链脂肪酸（SCFAs）的浓度。采用流式细胞仪珠子阵列测定血清细胞因子。采用16S rRNA基因测序探讨小鼠的肠道菌群组成。证实了6-MP在ALL小鼠模型中的抗肿瘤效果。6-MP给药后，炎性因子IL-6和TNFα的水平显著下降。盲肠内容物中的乙酸、丙酸和丁酸水平与IL-6（相关系数：乙酸，-0.24；丙酸，-0.26；丁酸，-0.17）和TNFα（相关系数：乙酸，-0.45；丙酸，-0.42；丁酸，-0.31）的变化呈负相关。f_Lachnospiraceae.g_ASF356和f_Peptococcaceae.g_uncultured的相对丰度变化与丁酸水平变化一致，与炎症水平的变化相反。肠道微生物群和其代谢物SCFAs，尤其是丁酸，对6-MP的抗炎反应起着重要作用，改善ALL的发展。© 2023 Elsevier B.V.保留所有权利。

Inflammasome has been reported to play an important role in the pathogenesis and progression of hematologic malignancies. As one of the backbone drugs for treating acute lymphoblastic leukemia (ALL), the anti-inflammatory effect of mercaptopurine (6-MP) and the impact of gut microbiome changes caused by 6-MP on anti-inflammasome remain unclear.We aimed to explore the association between 6-MP therapeutic effects and microbiome-involved inflammatory responses in ALL mice models.ALL murine model was built by i.v. injecting murine L1210 cells into DBA/2 mice (model group). Two weeks after cell injections, 6-MP was orally administrated for 14 days (6-MP group). Fecal samples of mice were collected at different time points. Cecum short-chain fatty acids (SCFAs) concentrations were determined by LC-MS/MS method. Serum cytokines were measured using a cytometric bead array. Gut microbiota composition in mice was explored using 16S rRNA gene sequencing.The anti-tumor effect of 6-MP was proved in ALL mice models. The levels of pro-inflammatory factors IL-6 and TNFα significantly decreased after the administration of 6-MP. Cecum contents' acetate, propionate, and butyrate levels were negatively correlated with IL-6 (correlation coefficient: acetate, -0.24; propionate, -0.26; butyrate, -0.17) and TNFα (correlation coefficient: acetate, -0.45; propionate, -0.42; butyrate, -0.31) changes. Relative abundance changes of f_Lachnospiraceae.g_ASF356 and f_Peptococcaceae.g_uncultured were in accordance with the changes of butyrate levels and opposite to the changes of pro-inflammatory levels.The anti-inflammatory response of 6-MP influenced by intestinal microbiota and its metabolites SCFAs, especially butyrate, played an essential role in improving ALL progression.Copyright © 2023 Elsevier B.V. All rights reserved.