Department of Rheumatology & Clinical Immunology, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Martinistrasse 46, 20246, Hamburg, Germany; German Center for Research on Infection, partner site Hamburg-Borstel-Lübeck-Riems, Germany.
J Autoimmun. 2019 Feb;97:29-39. doi: 10.1016/j.jaut.2018.10.005. Epub 2018 Nov 9.
Dysbiosis¸ i.e. changes in microbial composition at a mucosal interface, is implicated in the pathogenesis of many chronic inflammatory and autoimmune diseases. To assess the composition of the microbial upper respiratory tract (URT) community in patients with granulomatosis with polyangiitis (GPA), we used culture-independent high-throughput methods. In this prospective clinical study, nasal swabs were collected from patients with GPA, patients with rheumatoid arthritis (RA, disease control), and healthy controls. Nasal bacterial taxa were assessed using V3-V4 region 16S rRNA amplicon sequencing. Staphylococcus aureus, Haemophilus influenza, and entero- and rhinoviruses were detected using qPCR. Unbiased metagenomic RNA sequencing (UMERS) was performed in a subset of samples to determine the relative abundance of bacterial, fungal, and viral species. A trend toward reduced microbiome diversity was detected in GPA samples compared with healthy controls. The abundance of bacterial taxa and microbial richness were significantly decreased in GPA samples compared with RA samples. The relative abundance of bacterial families shifted, with increased Planococcaceae and decreased Moraxellaceae, Tissierellaceae, Staphylococcaceae, and Propionibacteriaceae in GPA and RA. Further, decreased abundance of Corynebacteriaceae, and Aerococcaceae was observed in GPA samples. Significantly more colonization of S. aureus was seen in the nasal microbiome of GPA compared with RA and healthy control samples. H. influenzae colonization was also observed in GPA samples. UMERS detected the presence of rhinoviral sequences in some GPA samples. Thus, our study uncovered changes in the URT microbial composition in patients with GPA and RA, suggesting that both immunosuppression and disease background affect the URT microbiome. Complex alterations of host-microbiome interactions in the URT could influence chronic endonasal inflammation in GPA.
生态失调，即黏膜界面微生物组成的改变，与许多慢性炎症和自身免疫性疾病的发病机制有关。为了评估 GPA 患者上呼吸道（URT）微生物群落的组成，我们使用了非培养的高通量方法。在这项前瞻性临床研究中，从 GPA 患者、类风湿关节炎（RA，疾病对照）患者和健康对照者中采集鼻拭子。使用 V3-V4 区 16S rRNA 扩增子测序评估鼻细菌分类群。使用 qPCR 检测金黄色葡萄球菌、流感嗜血杆菌以及肠病毒和鼻病毒。在一部分样本中进行无偏倚的宏基因组 RNA 测序（UMERS），以确定细菌、真菌和病毒种类的相对丰度。与健康对照组相比，GPA 样本中微生物多样性呈下降趋势。与 RA 样本相比，GPA 样本中细菌分类群的丰度和微生物丰富度显著降低。细菌科的相对丰度发生了变化，GPA 和 RA 样本中 Planococcaceae 增加，Moraxellaceae、Tissierellaceae、Staphylococcaceae 和 Propionibacteriaceae 减少。此外，还观察到 GPA 样本中 Corynebacteriaceae 和 Aerococcaceae 的丰度降低。与 RA 和健康对照组相比，GPA 患者的鼻腔微生物组中金黄色葡萄球菌的定植明显更多。在 GPA 样本中也观察到流感嗜血杆菌定植。UMERS 在一些 GPA 样本中检测到鼻病毒序列的存在。因此，我们的研究揭示了 GPA 和 RA 患者 URT 微生物组成的变化，表明免疫抑制和疾病背景都影响 URT 微生物组。URT 中宿主-微生物相互作用的复杂改变可能影响 GPA 的慢性鼻内炎症。
