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造血干细胞移植期间接受选择性或全肠道去污染治疗的儿童肠道微生物组的动态变化。

Dynamics of the Gut Microbiota in Children Receiving Selective or Total Gut Decontamination Treatment during Hematopoietic Stem Cell Transplantation.

机构信息

Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands.

Department of Medical Microbiology, Leiden University Medical Center, Leiden, the Netherlands; Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, the Netherlands.

出版信息

Biol Blood Marrow Transplant. 2019 Jun;25(6):1164-1171. doi: 10.1016/j.bbmt.2019.01.037. Epub 2019 Feb 5.

Abstract

Bloodstream infections and graft-versus-host disease are common complications after hematopoietic stem cell transplantation (HSCT) procedures, associated with the gut microbiota that acts as a reservoir for opportunistic pathogens. Selective gut decontamination (SGD) and total gut decontamination (TGD) during HSCT have been associated with a decreased risk of developing these complications after transplantation. However, because studies have shown conflicting results, the use of these treatments remains subject of debate. In addition, their impact on the gut microbiota is not well studied. The aim of this study was to elucidate the dynamics of the microbiota during and after TGD and to compare these with the dynamics of SGD. In this prospective, observational, single-center study fecal samples were longitudinally collected from 19 children eligible for allogenic HSCT (TGD, n=12; SGD, n=7), weekly during hospital admission and monthly after discharge. In addition, fecal samples were collected from 3 family stem cell donors. Fecal microbiota structure of patients and donors was determined by 16S rRNA gene amplicon sequencing. Microbiota richness and diversity markedly decreased during SGD and TGD and gradually increased after cessation of decontamination treatment. During SGD, gut microbiota composition was relatively stable and dominated by Bacteroides, whereas it showed high inter- and intraindividual variation and low Bacteroides abundance during TGD. In some children TGD allowed the genera Enterococcus and Streptococcus to thrive during treatment. A gut microbiota dominated by Bacteroides was associated with increased predicted activity of several metabolic processes. Comparing the microbiota of recipients and their donors indicated that receiving an SCT did not alter the patient's microbiota to become more similar to that of its donor. Overall, our findings indicate that SGD and TGD affect gut microbiota structure in a treatment-specific manner. Whether these treatments affect clinical outcomes via interference with the gut microbiota needs to be further elucidated.

摘要

血流感染和移植物抗宿主病是造血干细胞移植(HSCT)后常见的并发症,与肠道微生物群有关,后者是机会性病原体的储库。HSCT 期间的选择性肠道去污染(SGD)和全肠道去污染(TGD)与移植后这些并发症的风险降低有关。然而,由于研究结果存在矛盾,这些治疗方法的使用仍存在争议。此外,它们对肠道微生物群的影响尚未得到很好的研究。本研究旨在阐明 TGD 期间和之后微生物群的动态,并将其与 SGD 的动态进行比较。在这项前瞻性、观察性、单中心研究中,从 19 名适合异体 HSCT 的儿童中(TGD,n=12;SGD,n=7)纵向收集粪便样本,在住院期间每周收集一次,出院后每月收集一次。此外,还从 3 名亲缘供者中收集了粪便样本。通过 16S rRNA 基因扩增子测序确定患者和供者的粪便微生物群结构。SGD 和 TGD 期间,微生物丰富度和多样性明显降低,停止去污处理后逐渐增加。在 SGD 期间,肠道微生物群组成相对稳定,以拟杆菌为主,而在 TGD 期间,肠道微生物群组成表现出高度的个体间和个体内变异,拟杆菌丰度较低。在一些儿童中,TGD 允许肠球菌和链球菌属在治疗期间茁壮成长。以拟杆菌为主的肠道微生物群与几个代谢过程的预测活性增加有关。比较受者及其供者的微生物群表明,接受 SCT 并不会改变患者的微生物群,使其更类似于供者的微生物群。总的来说,我们的研究结果表明,SGD 和 TGD 以特定于治疗的方式影响肠道微生物群结构。这些治疗方法是否通过干扰肠道微生物群影响临床结局,需要进一步阐明。

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