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

点击翻译按钮获取中文摘要

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.