Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L vs 74.35 (33.50-139.50) μg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.
目的： 探讨粪菌移植（FMT）治疗糖皮质激素耐药胃肠道急性移植物抗宿主病（GI-aGVHD）的临床疗效。 方法： 纳入2017年3月至2022年3月期间在徐州医科大学附属淮安医院行异基因造血干细胞移植（allo-HSCT）后发生糖皮质激素耐药GI-aGVHD的29例血液病患者，其中19例行FMT治疗（FMT组），10例未接受FMT治疗（对照组）。观察疗效及安全性，分析FMT治疗前后肠道菌群丰度、淋巴细胞亚群比例、外周血炎症因子及GVHD生物标志物的变化。 结果： ①13例患者（68.4%）在FMT后临床症状达到完全缓解，对照组2例患者（20.0%）达到完全缓解，差异有统计学意义（P<0.05）。FMT后肠道微生物群多样性增加，并逐渐恢复至正常水平，未发生FMT相关感染。②与对照组比较，FMT组治疗后CD3(+)、CD8(+)细胞占比降低，CD4(+)、调节性T细胞（Treg）及CD4(+)/CD8(+)细胞比值升高（P值均<0.05），IL-6浓度低于对照组[4.15（1.91~5.71）ng/L对6.82（2.40~8.91）ng/L，P=0.040]，IL-10浓度高于对照组[12.11（5.69~20.36）ng/L对7.51（4.10~9.58）ng/L，P=0.024]。胰岛衍生蛋白3α（REG3α）在发生GI-aGVHD时明显升高，FMT组治疗后REG3α水平低于对照组[30.70（10.50~105.00）μg/L对74.35（33.50~139.50）μg/L，P=0.021]。 结论： FMT是糖皮质激素耐药GI-aGVHD的有效、安全治疗方法。FMT可促进肠道菌群多样性的恢复、调节炎症因子和上调Treg细胞表达。.
Keywords: Acute graft-versus-host disease; Allogeneic hematopoietic stem cell transplantation; Fecal microbiota transplantation; Inflammatory cytokines; Intestinal microbiota; Lymphocyte subpopulation.