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

同种异体造血干细胞移植是血液病（如白血病）的治疗选择。虽然同种异体造血干细胞移植具有潜在的治愈性，但它与不良事件的高发生率有关。同种异体造血移植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，近年来对接受同种异体造血干细胞移植患者肠道细菌微生物组的组成和动态进行了表征。由此可见，同种异体造血干细胞移植过程对细菌群落结构产生了严重的影响。反过来，随之而来的生态失调预示着不良后果，包括感染、GvHD和总死亡率。除了细菌之外，人类肠道还拥有多种真菌群落——真菌群系。与细菌组分相比，真菌组迄今尚未得到广泛的研究。然而，先前对接受同种异体移植的患者的研究指出了真菌组的重要作用：被念珠菌定植的患者GvHD发病率较高，相反，接受氟康唑治疗的患者GvHD发病率较低。该项目将首次分析接受同种异体造血干细胞移植的患者的组成和动态变化。将对约200名患者的粪便样本进行分析。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果（如感染、GvHD和死亡率）的决定因素。拟议项目的结果应该为预测这些结果（感染、GvHD、复发、生存）的真菌组数据的使用提供信息。它们也可能为通过重组或药物消除针对微生物群的真菌成分的治疗干预提供基础，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.