Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation
Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation
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DOI：
10.1200/jco.2016.70.3348
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发表时间：
2017-05-20
影响因子：
45.3
通讯作者：
van den Brink, Marcel R. M.
中科院分区：
文献类型：
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作者：
Peled, Jonathan U.;Devlin, Sean M.;van den Brink, Marcel R. M.
目的异基因造血细胞移植后死亡的主要原因是复发、移植物抗宿主病(GVHD)和感染。我们以前已经报道，肠道菌群的改变与移植物抗宿主病、菌血症和allo-HCT后总存活率降低有关。由于肠道细菌是包括抗肿瘤作用在内的全身免疫反应的有效调节者，我们假设肠道菌群的组成可能与allo-HCT后的复发有关。方法通过对前瞻性收集的粪便样本进行16S核糖体测序，对541例allo-HCT患者的肠道微生物区系进行了分析。我们在回溯性发现-验证队列研究中使用了病因特定的比例风险，在allo-HCT后2年的随访时间内，我们检验了微生物区系物种或相关物种组的丰度与疾病复发/进展的关系。结果验证集中以利莫氏真细菌为主的细菌群丰度越高，疾病复发/进展的风险就越低(风险比[HR]，每10倍丰度增加0.82；95%CI，0.71至0.95；P=0.009)。当根据有无这种细菌群对患者进行分类时，存在也与较少的疾病复发/进展相关(HR，0.52；95%CI，0.31至0.87；P=0.01)。在有和没有这组细菌的患者中，2年累计复发/进展发生率分别为19.8%和33.8%。这些相关性在多变量模型中仍然显著，在T细胞完全同种异体移植的受者中最强。结论我们发现在allo-HCT后肠道菌群中一组细菌的丰富程度与疾病的复发/进展之间存在关联。这些可能作为潜在的生物标志物或治疗靶点，以防止复发和提高生存后的allo-HCT。
PurposeThe major causes of mortality after allogeneic hematopoietic-cell transplantation (allo-HCT) are relapse, graft-versus-host disease (GVHD), and infection. We have reported previously that alterations in the intestinal flora are associated with GVHD, bacteremia, and reduced overall survival after allo-HCT. Because intestinal bacteria are potent modulators of systemic immune responses, including antitumor effects, we hypothesized that components of the intestinal flora could be associated with relapse after allo-HCT.MethodsThe intestinal microbiota of 541 patients admitted for allo-HCT was profiled by means of 16S ribosomal sequencing of prospectively collected stool samples. We examined the relationship between abundance of microbiota species or groups of related species and relapse/progression of disease during 2 years of follow-up time after allo-HCT by using cause-specific proportional hazards in a retrospective discovery-validation cohort study.ResultsHigher abundance of a bacterial group composed mostly of Eubacterium limosum in the validation set was associated with a decreased risk of relapse/progression of disease (hazard ratio [HR], 0.82 per 10-fold increase in abundance; 95% CI, 0.71 to 0.95; P = .009). When the patients were categorized according to presence or absence of this bacterial group, presence also was associated with less relapse/progression of disease (HR, 0.52; 95% CI, 0.31 to 0.87; P = .01). The 2-year cumulative incidences of relapse/progression among patients with and without this group of bacteria were 19.8% and 33.8%, respectively. These associations remained significant in multivariable models and were strongest among recipients of T-cell-replete allografts.ConclusionWe found associations between the abundance of a group of bacteria in the intestinal flora and relapse/progression of disease after allo-HCT. These might serve as potential biomarkers or therapeutic targets to prevent relapse and improve survival after allo-HCT.