Department of Hematology, Amsterdam UMC, Amsterdam, The Netherlands; Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity Institute, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Division of Infectious Diseases, First Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Clinical Development Infectious Diseases, BioNTech SE, Mainz, Germany.
Transplant Cell Ther. 2023 Jan;29(1):63.e1-63.e5. doi: 10.1016/j.jtct.2022.10.011. Epub 2022 Oct 21.
Disruption of the intestinal bacterial microbiota is frequently observed in the context of allogeneic hematopoietic cell transplantation (HCT) and is particularly pronounced in patients who develop graft-versus-host disease (GVHD). Donor fecal microbiota transplantation (FMT) restores gut microbial diversity and reduces GVHD in HCT recipients. The composition of the intestinal fungal community in patients with GVHD, and whether fungal taxa are transferred during FMT are currently unknown. We performed a secondary analysis of our clinical trial of FMT in patients with steroid-refractory GVHD with a focus on the mycobiota. We characterized the fecal mycobiota of 17 patients and healthy FMT donors using internal transcribed spacer amplicon sequencing. The donor who provided the majority of FMT material in our study represents an n-of-one study of the intestinal flora over time. In this donor, mycobiota composition fluctuated over time while the bacterial microbiota remained stable over 16 months. Fungal DNA was detected more frequently in baseline stool samples from patients with steroid-refractory GVHD than in patients with steroid-dependent GVHD. We could detect fungal taxa in the majority of samples but did not see evidence of mycobiota transfer from donor to recipient. Our study demonstrates the feasibility of profiling the mycobiota alongside the more traditional bacterial microbiota, establishes the methodology, and provides a first insight into the mycobiota composition of patients with GVHD.
肠道细菌菌群紊乱在异基因造血细胞移植（HCT）中经常观察到，特别是在发生移植物抗宿主病（GVHD）的患者中更为明显。供体粪便微生物群移植（FMT）可恢复肠道微生物多样性并减少 HCT 受者的 GVHD。GVHD 患者肠道真菌群落的组成，以及 FMT 期间是否转移真菌类群，目前尚不清楚。我们对 FMT 治疗类固醇难治性 GVHD 的临床试验进行了二次分析，重点关注真菌群。我们使用内部转录间隔区扩增子测序对 17 名患者和健康的 FMT 供体的粪便真菌群进行了表征。在本研究中，提供了大部分 FMT 材料的供体代表了随着时间的推移对肠道菌群的 n-of-one 研究。在该供体中，真菌菌群组成随时间波动，而细菌菌群在 16 个月内保持稳定。与依赖类固醇的 GVHD 患者相比，类固醇难治性 GVHD 患者的基线粪便样本中更频繁地检测到真菌 DNA。我们可以在大多数样本中检测到真菌类群，但没有证据表明供体到受者的真菌群转移。我们的研究证明了同时对真菌群和更传统的细菌菌群进行分析的可行性，建立了方法，并首次深入了解了 GVHD 患者的真菌群组成。
