Department of Medicine.
Department of Epidemiology, Biostatistics, and Informatics.
Ann Am Thorac Soc. 2019 Nov;16(11):1383-1391. doi: 10.1513/AnnalsATS.201904-299OC.
The oropharyngeal microbiome is a primary source of lung microbiota, contributes to lower respiratory infection, and is also a driver of oral health. We sought to understand oropharyngeal microbial communities in advanced lung disease, community dynamics after lung transplantation, and ecological features of dysbiosis. Oropharyngeal wash samples were obtained from individuals with end-stage disease awaiting transplantation ( = 22) and longitudinally from individuals at 6 weeks, 3 months, and 6 months after transplantation ( = 33), along with healthy control subjects ( = 14). Bacterial 16S and fungal internal transcribed spacer rRNA regions were deep-sequenced, and bacterial community respiratory patterns were imputed from taxonomic composition. Healthy subjects' oropharyngeal microbiomes showed a gradient of community types reflecting relative enrichment of strictly anaerobic, aerobic, or facultative anaerobic bacteria. Patients with end-stage lung disease showed severe dysbiosis by both taxonomic composition and respiration phenotypes, with reduced richness and diversity, increased facultative and decreased aerobic bacteria, and absence of communities characterized by obligate aerobes. In patients at 6 weeks and 3 months post-transplant, richness and diversity were intermediate between healthy and pretransplant subjects, with near-normal distribution of community types. However, by 6 months post-transplant, oropharyngeal wash resembled the low-diversity facultative-dominated profile of pretransplant subjects. Community ecotype correlated with abundance. End-stage lung disease is associated with marked upper respiratory tract dysbiosis involving both community structure and respiratory metabolism profiles of constituent bacteria. Dynamic changes occur after lung transplantation, with partial normalization early but later appearance of severe dysbiosis similar to pretransplant patients. Aberrant oropharyngeal communities may predispose to abnormal lung microbiota and infection risk both in advanced lung disease and after transplantation.
口咽微生物组是肺部微生物组的主要来源,会导致下呼吸道感染,也是口腔健康的驱动因素。我们试图了解晚期肺部疾病患者的口咽微生物群落、肺移植后的群落动态以及菌群失调的生态特征。采集了等待移植的终末期疾病患者( = 22)的口咽冲洗样本,并在移植后 6 周、3 个月和 6 个月时( = 33)以及健康对照者( = 14)进行了纵向采集。对细菌 16S 和真菌内部转录间隔区 rRNA 区进行了深度测序,并根据分类组成推断了细菌群落的呼吸模式。健康受试者的口咽微生物组显示出反映严格厌氧菌、需氧菌或兼性厌氧菌相对富集的群落类型梯度。终末期肺病患者的分类组成和呼吸表型均显示出严重的菌群失调,表现为丰富度和多样性降低,兼性菌增加而需氧菌减少,并且缺乏以专性需氧菌为特征的群落。移植后 6 周和 3 个月时,患者的丰富度和多样性处于健康和移植前受试者之间,群落类型分布接近正常。然而,移植后 6 个月时,口咽冲洗物类似于移植前患者的低多样性兼性优势型特征。群落生态型与丰度相关。终末期肺病与上呼吸道严重菌群失调有关,涉及群落结构和组成细菌的呼吸代谢特征。肺移植后会发生动态变化,早期部分正常化,但随后出现与移植前患者相似的严重菌群失调。异常的口咽群落可能会导致晚期肺部疾病和移植后异常的肺部微生物群和感染风险。