异基因造血干细胞移植术后微生物多样性的变化与肠道移植物抗宿主病的关系

Relationship Between the Change of Microbial Diversity and Gastrointestinal Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation

目的:探讨异基因造血干细胞移植术后患者肠道微生物多样性的变化及其与肠道(gastrointestinal,GI)移植物抗宿主病(graft-versus-host disease,GVHD)的关系。方法:收集65例血液病患者移植前2周(移植前组),移植后1个月(移植后组)及GI GVHD发生时的粪便样品;同时收集26例供者及10例健康人(对照组)的粪便样品;提取粪便微生物中的16S rRNA并扩增其V4可变区,扩增产物在Illumina HiSeq 2500平台测序,对测序结果进行分析对比。结果:移植前组微生物多样性为5.70(3.74,10.60),对照组为7.30(4.89,11.41),2组比较差异无统计学意义;移植后组微生物多样性为3.88(2.39,6.49),低于对照组及移植前组。移植后微生物多样性在不发生GI GVHD的患者中为4.24(2.47,7.16),随后发生GI GVHD的患者中为2.90(1.48,5.64),2组比较差异无统计学意义;GI GVHD发生时的患者中微生物多样性为2.13(1.76,3.75),低于不发生GI GVHD的患者。结论:异基因造血干细胞移植术后肠道微生物多样性降低,并与GI GVHD相关。

Objective: To investigate the change of microbial diversity and its relation with gastrointestinal(GI) graft-versus-host disease(GVHD) following allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods: Fecal samples were collected at the time point of 2 weeks before transplantation(pre-transplant group), 1 month after transplantation(post-tranplant group) and onset of GI GVHD in 65 hematonosis patients, which were also collected in 26 donors and 10 healthy subjects(control group). 16 S rRNA was extracted from fecal microbiotas whose V4 variable region was amplified. The amplification products were sequenced in Illumina HiSeq 2500 platform, and the sequencing results were analyzed and compared. Results: The microbial diversity was 5.70(3.74, 10.60)in pre-transplant group, 7.30(4.89, 11.41)in control group, and the differences between them were not statistically significant. The microbial diversity was 3.88(2.39, 6.49)in post-transplant group, lower than that in control group and pre-transplant group. After transplantation, the microbial diversity was 4.24(2.47, 7.16)in the patients without GI GVHD, while the microbial diverosity was 2.90(1.48, 5.64) in patients subsequently suffered from GI GVHD, but the differences between them were not statistically significant. The microbial diversity was 2.13(1.76, 3.75)onset of GI GVHD, which was lower than that without GI GVHD. Conclusion: Intestinal microbial diversity decreases after allo-HSCT, and is associated with with Gl GVHD.