Update in clinical and mouse microbiota research in allogeneic haematopoietic cell transplantation.
Update in clinical and mouse microbiota research in allogeneic haematopoietic cell transplantation.
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DOI：
10.1097/moh.0000000000000616
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发表时间：
2020-11
影响因子：
3.2
通讯作者：
Peled JU
中科院分区：
文献类型：
--
作者：
Lindner S;Peled JU
肠道微生物群在肠道稳态和免疫调节中起着关键作用，并且已被认为是接受异基因造血细胞移植（allo-HCT）的患者的临床结果的预测因子，特别是小鼠模型中移植物抗宿主病（GVHD）严重程度的决定因素。由于GVHD是allo-HCT后非复发死亡率（NRM）的最重要原因，因此了解修饰微生物群可以预防或降低GVHD严重程度的机制将代表重要的进展。在全球范围内观察到微生物群损伤，植入前后的更高多样性与更低的死亡率相关。乳糖是一种促进异基因HCT后肠球菌扩增的饮食因子，其本身与患者中GVHD的死亡率相关，并加剧小鼠中的GVHD。细菌和真菌血流感染之前，肠道定植有相应的生物体，支持肠道作为许多血流感染的来源。代谢组学分析研究表明，GVHD与粪便和血浆微生物衍生分子的变化有关。在这篇综述中，我们强调了一些最新的和重要的发现，在临床和小鼠微生物群的研究，因为它涉及到allo-HCT。其中许多已经被转化为临床试验，有可能改变未来的病人护理实践。
The intestinal microbiota plays a critical role in intestinal homeostasis and immune regulation and has been recognized as a predictor of clinical outcome in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) and specifically a determinant of the severity of graft-versus-host disease (GVHD) in mouse models. As GVHD is the most important cause of non-relapse mortality (NRM) after allo-HCT, understanding the mechanisms by which modifying the microbiota may prevent or decrease the severity of GVHD would represent an important advance. Microbiota injury was observed globally and higher diversity at periengraftment was associated with lower mortality. Lactose is a dietary factor that promotes post-allo-HCT Enterococcus expansion, which is itself associated with mortality from GVHD in patients and exacerbates GVHD in mice. Bacterial and fungal bloodstream infections are preceded by intestinal colonization with a corresponding organism, supporting the gut as a source for many bloodstream infections. Metabolomic profiling studies showed that GVHD is associated with changes in fecal and plasma microbiota-derived molecules. In this review, we highlight some of the most recent and important findings in clinical and mouse microbiota research as it relates to allo-HCT. Many of these are already being translated into clinical trials that have the potential to change the future practice in the care of patients.