Division of Rheumatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Vasculitis Translational Research Program, National Institutes of of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA.
Ann Rheum Dis. 2018 Oct;77(10):1448-1453. doi: 10.1136/annrheumdis-2018-213645. Epub 2018 Jul 11.
Prior studies have suggested a potential link between nasal microbes and granulomatosis with polyangiitis (GPA; Wegener's), but these studies relied on culture-dependent methods. This study comprehensively examined the entire community of nasal microbiota (bacteria and fungi) in participants with GPA compared with healthy controls using deep sequencing methods.
16S rRNA and internal transcribed spacer gene sequencing were performed on nasal microbial DNA isolated from nasal swabs of 60 participants with GPA and 41 healthy controls. Alpha and beta diversity were assessed as well as the relative abundance of the most abundant bacterial and fungal taxa. The effects of covariates including disease activity and immunosuppressive therapies on microbial composition were evaluated.
Compared with controls, participants with GPA had a significantly different microbial composition (weighted UniFrac p=0.04) and lower relative abundance of and (for both, false discovery rate-corrected p=0.02). Disease activity in GPA was associated with a lower abundance of fungal order compared with participants with GPA in remission (p=0.04) and controls (p=0.01). Use of non-glucocorticoid immunosuppressive therapy was associated with 'healthy' nasal microbiota while participants with GPA who were off immunosuppressive therapy had more dysbiosis (weighted UniFrac p=0.01). No difference in the relative abundance of was observed between GPA and controls.
GPA is associated with an altered nasal microbial composition, at both the bacterial and fungal levels. Use of immunosuppressive therapies and disease remission are associated with healthy microbial communities.
先前的研究表明，鼻腔微生物与肉芽肿性多血管炎（GPA；韦格纳氏）之间可能存在潜在联系，但这些研究依赖于基于培养的方法。本研究采用深度测序方法，全面比较了 GPA 患者和健康对照者鼻腔微生物群（细菌和真菌）的整个群落。
对 60 名 GPA 患者和 41 名健康对照者鼻腔拭子中分离的鼻腔微生物 DNA 进行 16S rRNA 和内部转录间隔区基因测序。评估了 alpha 和 beta 多样性以及最丰富的细菌和真菌分类群的相对丰度。评估了包括疾病活动度和免疫抑制治疗在内的协变量对微生物组成的影响。
与对照组相比，GPA 患者的微生物组成存在显著差异（加权 UniFrac，p=0.04），和 的相对丰度较低（两者均经错误发现率校正，p=0.02）。与缓解期 GPA 患者（p=0.04）和对照组（p=0.01）相比，GPA 患者的疾病活动度与真菌目 的丰度较低相关。非糖皮质激素免疫抑制治疗与“健康”的鼻腔微生物群相关，而停用免疫抑制治疗的 GPA 患者则存在更多的微生态失调（加权 UniFrac，p=0.01）。GPA 患者和对照组之间的 相对丰度没有差异。
GPA 与鼻腔微生物组成的改变有关，包括细菌和真菌水平。免疫抑制治疗的使用和疾病缓解与健康的微生物群落有关。
