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造血干细胞移植后肠道菌群变化与肠道急性移植物抗宿主病关系的探讨

Exploration of the relationship between intestinal flora changes and gut acute graft-versus-host disease after hematopoietic stem cell transplantation.

作者信息

Song Aiyun, Shen Nan, Gan Chi, Luo Changying, Luo Chengjuan, Wang Jianmin, Cao Qing, Chen Jing

机构信息

Department of Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Infectious Disease, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Transl Pediatr. 2021 Feb;10(2):283-295. doi: 10.21037/tp-20-208.

Abstract

BACKGROUND

Acute graft-versus-host disease (aGVHD) is a life-threatening factor for post-hematopoietic stem cell transplantation (HSCT) patients. To investigate the relationship between intestinal flora changes and gut aGVHD after HSCT, we performed this cross-sectional study.

METHODS

We selected children from our medical center from July 2016 to January 2017. Fifty-six samples from 42 patients and 6 samples from normal children met the study criteria and were analyzed. Fecal 16S RNA sequencing was completed before transplantation or on days 7, 28 or 100 post-transplantation. The intestinal infection and GVHD clinical data were retrospectively analyzed, and the survival risk factors were analyzed. Correlation analysis was performed with the feces bioinformatic data.

RESULTS

The GVHD group alpha diversity was the lowest, which was significantly different than that of the non-diarrhea group (P value=0.032). A richer posttransplantation relative abundance of was conducive to survival, while that of and was not. Similarly, a rich relative abundance of , and in the intestinal flora before HSCT contributed to patient death thereafter. Regarding diarrhea, the GVHD group exhibited a richer and relative abundances, which showed strong correlations with diarrhea severity. , and were richer in relative abundance in the intestinal infection group and correlated with pretransplant characteristics.

CONCLUSIONS

The gut microbiota diversity was lowest when gut aGVHD occurred, which was consistent with the clinically higher mortality rate and greater treatment difficulty. played an important role in gut aGVHD and diarrhea severity. led to infectious diarrhea after HSCT. Specific bacteria were biomarkers for survival: , and from the intestinal flora after HSCT and , and before HSCT.

摘要

背景

急性移植物抗宿主病(aGVHD)是造血干细胞移植(HSCT)后患者的一个危及生命的因素。为了研究HSCT后肠道菌群变化与肠道aGVHD之间的关系,我们开展了这项横断面研究。

方法

我们选取了2016年7月至2017年1月在我们医疗中心的儿童。来自42例患者的56份样本和来自正常儿童的6份样本符合研究标准并进行了分析。在移植前或移植后第7、28或100天完成粪便16S RNA测序。对肠道感染和GVHD临床数据进行回顾性分析,并分析生存风险因素。对粪便生物信息数据进行相关性分析。

结果

GVHD组的α多样性最低,与非腹泻组相比有显著差异(P值=0.032)。移植后相对丰度较高的[具体菌群名称未给出]有利于生存,而[具体菌群名称未给出]和[具体菌群名称未给出]则不然。同样,HSCT前肠道菌群中[具体菌群名称未给出]、[具体菌群名称未给出]和[具体菌群名称未给出]的相对丰度较高会导致患者随后死亡。关于腹泻,GVHD组的[具体菌群名称未给出]和[具体菌群名称未给出]相对丰度较高,与腹泻严重程度密切相关。肠道感染组中[具体菌群名称未给出]、[具体菌群名称未给出]和[具体菌群名称未给出]的相对丰度较高,且与移植前特征相关。

结论

肠道aGVHD发生时肠道微生物群多样性最低,这与临床上较高的死亡率和较大的治疗难度一致。[具体菌群名称未给出]在肠道aGVHD和腹泻严重程度中起重要作用。[具体菌群名称未给出]导致HSCT后感染性腹泻。特定细菌是生存的生物标志物:HSCT后肠道菌群中的[具体菌群名称未给出]、[具体菌群名称未给出]和[具体菌群名称未给出]以及HSCT前的[具体菌群名称未给出]、[具体菌群名称未给出]和[具体菌群名称未给出]。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd9/7944174/a0c67b49d195/tp-10-02-283-f1.jpg

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