Upper Respiratory Dysbiosis with a Facultative-Dominated Ecotype in Advanced Lung Disease and Dynamic Change after Lung Transplant.

Abstract

RATIONALE\nThe oropharyngeal microbiome is a primary source of lung microbiota and contributes to lower respiratory infection, and is also a driver of oral health.\n\n\nOBJECTIVES\nWe sought to understand oropharyngeal microbial communities in advanced lung disease, community dynamics following lung transplantation, and ecological features of dysbiosis.\n\n\nMETHODS\nOropharyngeal wash (OW) samples were obtained from individuals with end-stage disease awaiting transplantation (n=22), and longitudinally from individuals at 6 weeks, 3 months and 6 months following transplantation (n=33), along with healthy controls (n=14). Bacterial 16S and fungal ITS rRNA regions were deep-sequenced, and bacterial community respiratory patterns were imputed from taxonomic composition.\n\n\nRESULTS\nHealthy subjects oropharyngeal microbiomes showed a gradient of community types reflecting relative enrichment of strictly anaerobic, aerobic or facultative anaerobic bacteria. End-stage lung disease patients 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 pre-transplant subjects, with near-normal distribution of community types. However by six months post-transplant OW resembled the low-diversity facultative-dominated profile of pre-transplant subjects. Community ecotype correlated with Candida abundance.\n\n\nCONCLUSIONS\nEnd-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 pre-transplant patients. Aberrant oropharyngeal communities may predispose to abnormal lung microbiota and infection risk both in advanced lung disease and after transplantation.