BACKGROUND Relationships between microbiota composition and clinical outcomes after allogeneic hematopoietic-cell transplantation have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable. METHODS The microbiota composition of fecal samples obtained from patients who were undergoing allogeneic hematopoietic-cell transplantation at four centers was profiled by means of 16S ribosomal RNA gene sequencing. In an observational study, we examined associations between microbiota diversity and mortality using Cox proportional-hazards analysis. For stratification of the cohorts into higher- and lower-diversity groups, the median diversity value that was observed at the study center in New York was used. In the analysis of independent cohorts, the New York center was cohort 1, and three centers in Germany, Japan, and North Carolina composed cohort 2. Cohort 1 and subgroups within it were analyzed for additional outcomes, including transplantation-related death. RESULTS We profiled 8767 fecal samples obtained from 1362 patients undergoing allogeneic hematopoietic-cell transplantation at the four centers. We observed patterns of microbiota disruption characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota was associated with a lower risk of death in independent cohorts (cohort 1: 104 deaths among 354 patients in the higher-diversity group vs. 136 deaths among 350 patients in the lower-diversity group; adjusted hazard ratio, 0.71; 95% confidence interval [CI], 0.55 to 0.92; cohort 2: 18 deaths among 87 patients in the higher-diversity group vs. 35 deaths among 92 patients in the lower-diversity group; adjusted hazard ratio, 0.49; 95% CI, 0.27 to 0.90). Subgroup analyses identified an association between lower intestinal diversity and higher risks of transplantation-related death and death attributable to graft-versus-host disease. Baseline samples obtained before transplantation already showed evidence of microbiome disruption, and lower diversity before transplantation was associated with poor survival. CONCLUSIONS Patterns of microbiota disruption during allogeneic hematopoietic-cell transplantation were similar across transplantation centers and geographic locations; patterns were characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota at the time of neutrophil engraftment was associated with lower mortality. (Funded by the National Cancer Institute and others.).

中文翻译：

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微生物群作为同种异体造血细胞移植死亡率的预测因子。

背景 单中心研究描述了异基因造血细胞移植后微生物群组成与临床结果之间的关系。人类微生物群落组成的地理差异和机构间临床实践的差异提出了这些关联是否具有普遍性的问题。方法 通过 16S 核糖体 RNA 基因测序分析从四个中心接受同种异体造血细胞移植的患者获得的粪便样本的微生物群组成。在一项观察性研究中，我们使用 Cox 比例风险分析检查了微生物群多样性与死亡率之间的关联。为了将队列分为更高和更低多样性的群体，使用了在纽约研究中心观察到的多样性中值。在独立队列分析中，纽约中心是队列 1，德国、日本和北卡罗来纳州的三个中心组成队列 2。队列 1 和其中的亚组分析了其他结局，包括移植相关死亡。结果 我们分析了从四个中心接受同种异体造血细胞移植的 1362 名患者获得的 8767 份粪便样本。我们观察到微生物群破坏的模式，其特征是多样性的丧失和单一分类群的支配。在独立队列中，肠道微生物群的较高多样性与较低的死亡风险相关（队列 1：较高多样性组的 354 名患者中有 104 人死亡，而较低多样性组的 350 名患者中有 136 人死亡；调整后的风险比，0.71；95% 置信区间 [CI]，0.55 至 0.92；队列 2：较高多样性组的 87 名患者中有 18 人死亡，而较低多样性组中的 92 名患者中有 35 人死亡；调整后的风险比，0.49；95% CI，0.27 至 0.90）。亚组分析确定了肠道多样性较低与移植相关死亡和移植物抗宿主病死亡风险较高之间的关联。移植前获得的基线样本已经显示出微生物群破坏的证据，移植前较低的多样性与较差的存活率有关。结论 同种异体造血细胞移植期间微生物群破坏的模式在移植中心和地理位置之间是相似的；模式的特点是多样性的丧失和单一类群的支配。中性粒细胞植入时肠道微生物群的多样性与较低的死亡率相关。（由国家癌症研究所等资助。）。