Gurer-Kluge Ekin Ece, Oguz Fatma Savran, Aktas Zerrin, Besisik Sevgi Kalayoglu, Sezerman Ugur, Oncul Oral, Gulbas Zafer
Istanbul University, Institute of Health Sciences, Istanbul, Turkey; Istanbul University, Istanbul Faculty of Medicine/ Department of Medical Biology, Istanbul, Turkey.
Istanbul University, Istanbul Faculty of Medicine/ Department of Medical Biology, Istanbul, Turkey.
Hematol Transfus Cell Ther. 2025 Dec 12;48(1):106074. doi: 10.1016/j.htct.2025.106074.
This study aims to support our hypothesis regarding compositional changes in the intestinal microbiota by characterizing these changes through pre- and post-transplantation analyses. Additionally, it seeks to determine whether monitoring the intestinal flora could provide predictive or therapeutic insights into graft versus host disease.
This study included adult patients who underwent allogeneic hematopoietic stem cell transplantation. Microbiota assessments were performed through stool analyses. Stool samples were collected twice: once before transplantation and once after engraftment. Following nucleic acid isolation, the samples were processed using New Generation Sequencing. Microbiota-associated pathways were examined using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Statistical analyses were performed using R statistical software. In addition to microbiota analysis, resistance genes common in Gram-negative bacteria in the region (such as OXA-48-like, KPC-like, NDM-like, and CTX-M-like) were identified via classical polymerase chain reaction in stool samples collected after transplantation. The pathways were analyzed using the KEGG database.
Fifteen transplant recipients participated in the study. The Proteobacteria phylum increased in patients who tested positive for the CTXM-1 group and OXA-48-like resistance genes. Blautia caecimuris and Enterococcus exhibited significant changes following transplantation, while Tyzzerella spp. and Dialister spp. showed significant alterations after the onset of graft-versus-host disease. A marked change in Eubacterium spp. was also noted in patients with disease relapse. Two key metabolic pathways-acridone alkaloid biosynthesis and the D-arginine and D-ornithine metabolism-were associated with clinical outcomes.
This study demonstrates that allogeneic hematopoietic stem cell transplants lead to significant alterations in intestinal microbiota composition, including increased pathogenic bacteria associated with graft-versus-host disease exacerbation. These findings suggest that microbiota monitoring may be a promising strategy for the prevention and treatment of graft-versus-host disease. Moreover, modulation of specific microbial metabolic pathways may influence disease clinical outcomes. As the first study of its kind conducted within the Turkish population, this research contributes novel insights to the existing literature and highlights the potential of microbiota-based approaches in post-transplant patient management.
本研究旨在通过移植前和移植后的分析来表征肠道微生物群的组成变化，以支持我们关于肠道微生物群组成变化的假设。此外，它试图确定监测肠道菌群是否能为移植物抗宿主病提供预测性或治疗性见解。
本研究纳入了接受异基因造血干细胞移植的成年患者。通过粪便分析进行微生物群评估。粪便样本采集两次：一次在移植前，一次在植入后。核酸分离后，使用新一代测序对样本进行处理。使用京都基因与基因组百科全书（KEGG）数据库检查与微生物群相关的途径。使用R统计软件进行统计分析。除了微生物群分析外，还通过经典聚合酶链反应在移植后采集的粪便样本中鉴定该地区革兰氏阴性菌中常见的耐药基因（如OXA-48样、KPC样、NDM样和CTX-M样）。使用KEGG数据库对途径进行分析。
15名移植受者参与了该研究。CTX-M-1组和OXA-48样耐药基因检测呈阳性的患者中变形菌门增加。盲肠布劳特氏菌和肠球菌在移植后表现出显著变化，而泰泽氏菌属和戴阿利斯特氏菌属在移植物抗宿主病发作后显示出显著改变。疾病复发患者中真杆菌属也有明显变化。两个关键代谢途径——吖啶酮生物碱生物合成以及D-精氨酸和D-鸟氨酸代谢——与临床结果相关。
本研究表明，异基因造血干细胞移植会导致肠道微生物群组成发生显著变化，包括与移植物抗宿主病加重相关的病原菌增加。这些发现表明，微生物群监测可能是预防和治疗移植物抗宿主病的一种有前景的策略。此外，调节特定的微生物代谢途径可能会影响疾病的临床结果。作为在土耳其人群中进行的同类研究中的第一项，本研究为现有文献提供了新的见解，并突出了基于微生物群的方法在移植后患者管理中的潜力。
