Stool Microbiota at Neutrophil Recovery Is Predictive for Severe Acute Graft vs Host Disease After Hematopoietic Cell Transplantation.

Stool Microbiota at Neutrophil Recovery Is Predictive for Severe Acute Graft vs Host Disease After Hematopoietic Cell Transplantation.
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DOI:
10.1093/cid/cix699
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发表时间:
2017-11-29
期刊:
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子:
--
通讯作者:
Fredricks DN
Fredricks DN
中科院分区:
其他
文献类型:
--
作者:
Golob JL;Pergam SA;Srinivasan S;Fiedler TL;Liu C;Garcia K;Mielcarek M;Ko D;Aker S;Marquis S;Loeffelholz T;Plantinga A;Wu MC;Celustka K;Morrison A;Woodfield M;Fredricks DN

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中性粒细胞恢复时粪便微生物群中的低α多样性与增加的严重移植物抗宿主病(GVHD)、口腔放线菌或厚壁菌门的更大丰度以及中性粒细胞恢复时粪便微生物群中肠毛螺菌科的减少的丰度相关,所述增加的严重GVHD与增加的严重GVHD相关。移植物抗宿主病(GVHD)是异基因造血细胞移植(HCT)后常见的疾病。GVHD死亡风险与移植后早期粪便微生物群中的低细菌多样性有关;然而,与GVHD风险相关的特定物种仍然定义不清。我们前瞻性地收集了66例接受HCT的患者的连续每周粪便样本,从移植前开始,每周一次,直到移植后100天,共694例HCT受者的观察结果。我们使用16S rRNA基因聚合酶链反应与简并引物,然后通过高通量测序来评估随时间推移粪便样本中细菌分类群的序列读数的相对丰度。HCT接受者的肠道微生物群是高度动态的,在短时间尺度上常见的分类群的丢失和出现。与先前的研究一样,GVHD与粪便微生物群的α多样性较低有关。在HCT后中性粒细胞恢复时,粪便中口腔放线菌和口腔厚壁菌门的存在与随后的GVHD呈正相关;毛螺菌科呈负相关。细菌种类的梯度(阳性相关物的相对丰度的总和减去阴性相关物的相对丰度的总和的差)是随后的严重急性GVHD的最具预测性的(0.83的曲线下的受试者操作者特征面积)。在本研究中,HCT后中性粒细胞恢复时间前后的粪便微生物群可预测严重急性GVHD的后续发展。
Low alpha diversity in stool microbiota at neutrophil recovery associates with increased severe graft-versus-host disease (GVHD), greater abundance of oral Actinobacteria or Firmicutes, and decreased abundance of intestinal Lachnospiraceae in stool microbiota at neutrophil recovery associated with increased severe GVHD. Graft-versus-host disease (GVHD) is common after allogeneic hematopoietic cell transplantation (HCT). Risk for death from GVHD has been associated with low bacterial diversity in the stool microbiota early after transplant; however, the specific species associated with GVHD risk remain poorly defined. We prospectively collected serial weekly stool samples from 66 patients who underwent HCT, starting pre-transplantation and continuing weekly until 100 days post-transplant, a total of 694 observations in HCT recipients. We used 16S rRNA gene polymerase chain reaction with degenerate primers, followed by high-throughput sequencing to assess the relative abundance of sequence reads from bacterial taxa in stool samples over time. The gut microbiota was highly dynamic in HCT recipients, with loss and appearance of taxa common on short time scales. As in prior studies, GVHD was associated with lower alpha diversity of the stool microbiota. At neutrophil recovery post-HCT, the presence of oral Actinobacteria and oral Firmicutes in stool was positively correlated with subsequent GVHD; Lachnospiraceae were negatively correlated. A gradient of bacterial species (difference of the sum of the relative abundance of positive correlates minus the sum of the relative abundance of negative correlates) was most predictive (receiver operator characteristic area under the curve of 0.83) of subsequent severe acute GVHD. The stool microbiota around the time of neutrophil recovery post-HCT is predictive of subsequent development of severe acute GVHD in this study.
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