Research Group for Genomic Epidemiology, Technical University of Denmark, Kongens Lyngby, Denmark.
Present address: Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark.
Microbiome. 2021 Jun 28;9(1):148. doi: 10.1186/s40168-021-01100-2.
Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) exhibit changes in their gut microbiota and are experiencing a range of complications, including acute graft-versus-host disease (aGvHD). It is unknown if, when, and under which conditions a re-establishment of microbial and immunological homeostasis occurs. It is also unclear whether microbiota long-term dynamics occur at other body sites than the gut such as the mouth or nose. Moreover, it is not known whether the patients' microbiota prior to HSCT holds clues to whether the patient would suffer from severe complications subsequent to HSCT. Here, we take a holobiont perspective and performed an integrated host-microbiota analysis of the gut, oral, and nasal microbiota in 29 children undergoing allo-HSCT.
The bacterial diversity decreased in the gut, nose, and mouth during the first month and reconstituted again 1-3 months after allo-HSCT. The microbial community composition traversed three phases over 1 year. Distinct taxa discriminated the microbiota temporally at all three body sides, including Enterococcus spp., Lactobacillus spp., and Blautia spp. in the gut. Of note, certain microbial taxa appeared already changed in the patients prior to allo-HSCT as compared with healthy children. Acute GvHD occurring after allo-HSCT could be predicted from the microbiota composition at all three body sites prior to HSCT. The reconstitution of CD4 T cells, T17, and B cells was associated with distinct taxa of the gut, oral, and nasal microbiota.
This study reveals for the first time bacteria in the mouth and nose that may predict aGvHD. Monitoring of the microbiota at different body sites in HSCT patients and particularly through involvement of samples prior to transplantation may be of prognostic value and could assist in guiding personalized treatment strategies. The identification of distinct bacteria that have a potential to predict post-transplant aGvHD might provide opportunities for an improved preventive clinical management, including a modulation of microbiomes. The host-microbiota associations shared between several body sites might also support an implementation of more feasible oral and nasal swab sampling-based analyses. Altogether, the findings suggest that the microbiota and host factors together could provide actionable information to guiding precision medicine. Video Abstract.
接受异基因造血干细胞移植（HSCT）的患者其肠道微生物群会发生变化，并出现多种并发症，包括急性移植物抗宿主病（aGvHD）。目前尚不清楚微生物和免疫稳态是否会重建，以及在何时、在何种条件下会重建。也不清楚微生物群的长期动态是否会发生在肠道以外的其他部位，如口腔或鼻腔。此外，尚不清楚患者 HSCT 前的微生物群是否可以提供线索，了解患者在 HSCT 后是否会遭受严重并发症。在这里，我们从整体生物的角度出发，对 29 名接受异基因 HSCT 的儿童的肠道、口腔和鼻腔微生物群进行了宿主-微生物群综合分析。
在第一个月，肠道、鼻腔和口腔中的细菌多样性下降，在 allo-HSCT 后 1-3 个月再次重建。微生物群落组成在 1 年内经历了三个阶段的变化。在所有三个身体部位，包括肠道中的肠球菌属、乳杆菌属和布劳特氏菌属，都有独特的分类群随时间区分微生物群。值得注意的是，与健康儿童相比，某些微生物群在 allo-HSCT 前就已经发生了变化。allo-HSCT 后发生的急性 GvHD 可以从 HSCT 前所有三个身体部位的微生物群组成来预测。CD4 T 细胞、T17 和 B 细胞的重建与肠道、口腔和鼻腔微生物群的特定分类群有关。
本研究首次揭示了口腔和鼻腔中的细菌可能预测 aGvHD。监测 HSCT 患者不同身体部位的微生物群，特别是通过移植前样本的参与，可能具有预后价值，并有助于指导个性化治疗策略。确定具有预测移植后 aGvHD 潜力的特定细菌可能为改善预防临床管理提供机会，包括微生物组的调节。几个身体部位之间的宿主-微生物群关联也可能支持实施更可行的口腔和鼻腔拭子采样分析。总的来说，这些发现表明，微生物群和宿主因素可以共同提供有价值的信息，指导精准医学。视频摘要。
