The mycobiome and clinical outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation.

异基因造血干细胞移植（allo-HSCT）是治疗白血病等血液系统疾病的一种选择。虽然allo-HSCT具有潜在的治愈性，但它与不良事件的高发生率相关。allo-HSCT后的主要并发症包括感染和移植物抗宿主病（GvHD）。随着高通量测序技术的出现，近年来已经表征了接受allo-HSCT的患者的肠道细菌微生物组的组成和动力学。可以表明，细菌群落结构受到allo-HSCT过程的严重影响。反过来，随之而来的生态失调预示着不良后果，包括感染、GvHD和总体死亡率。除了细菌外，人类肠道还拥有多种真菌群落-真菌群落。与细菌组分相比，真菌生物群系迄今尚未被广泛研究。然而，之前对接受allo-HSCT的患者的研究指出了真菌生物群的重要作用：念珠菌定殖的患者具有较高的GvHD发生率，相反，氟康唑治疗的患者具有较低的GvHD发生率。本项目将首次分析接受allo-HSCT患者的组成和动态变化。粪便样本。将对200名患者进行分析。真菌群落结构将通过真菌ITS 1的扩增和测序以及随后与参考数据库的比较来确定。第二个目的是确定真菌群落结构或特定真菌成分是否是患者不良结局（如感染，GvHD和死亡率）的决定因素。拟议项目的结果应告知使用真菌生物群数据预测这些结果（感染，GvHD，复发，生存）。它们还可以通过重建或通过药物消除来提供针对微生物群的真菌组分的治疗干预的基础，以改善患者相关的结果。

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is treatment option for hematological diseases such as leukemias. While allo-HSCT is potentially curative, it is associated with a high incidence of adverse events. Major complications after allo-HSCT encompass infections and graft-versus-host-disease (GvHD). With the advent of high-throughput sequencing techniques, the composition and dynamics of the intestinal bacterial microbiome in patients undergoing allo-HSCT have been characterized in the recent years. It could be shown that the bacterial community structure is severely impacted by the allo-HSCT process. In turn the ensuing dysbiosis is predictive of adverse outcomes, including infections, GvHD and overall mortality. Besides bacteria, the human intestine hosts also a diverse community of fungi – the mycobiome. In contrast to the bacterial components, the mycobiome has not been extensively studies so far. However, prior studies on patients undergoing allo-HSCT point to an important role of the mycobiome: patients colonized with Candida have a higher incidence of GvHD and conversely patients treated with fluconazole have a lower incidence of GvHD. This project will be the first to analyse the composition and the dynamic changes in patients undergoing allo-HSCT. Stool samples of ca. 200 patients will be analysed. The fungal community structure will be determined by amplification and sequencing of fungal ITS 1 and subsequent comparison to reference databases. A second aim is to determine whether the fungal community structure or specific fungal components are determinants of adverse patient outcomes (such as infections, GvHD, and mortality). The results of the proposed project should inform the use of mycobiome data in predicting these outcomes (infection, GvHD, relapse, survival). They may also provide the base for therapeutic interventions targeting the fungal components of the microbiota by reconstitution or by pharmaceutical elimination to improve patient-related outcomes.