Lung-enriched Organisms and Aberrant Bacterial and Fungal Respiratory Microbiota after Lung Transplant

Rationale: Long-term survival after lung transplantation is limited by infectious complications and by bronchiolitis obliterans syndrome (BOS), a formof chronic rejection linked inpart tomicrobial triggers. Objectives: To definemicrobial populations in the respiratory tract of transplant patients comprehensively using unbiased high-density sequencing. Methods: Lung was sampled by bronchoalveolar lavage (BAL) and upper respiratory tract by oropharyngeal wash (OW). Bacterial 16S rDNAand fungal internal transcribed spacer sequencingwasused to profileorganismspresent.Outlieranalysisplotsdefiningtaxaenriched in lung relative to OWwere used to identify bacteria enriched in lung against a background of oropharyngeal carryover. Measurements and Main Results: Lung transplant recipients had higher bacterial burden in BAL than control subjects, frequent appearance of dominant organisms, greater distance between communities in BAL and OW indicating more distinct populations, and decreased respira-tory tract microbial richness and diversity. Fungal populations were typically dominated by Candida in both sites or by Aspergillus in BAL but notOW. 16S outlier analysis identified lung-enriched taxa indicat-ingbacteria replicatinginthe lowerrespiratorytract. Insomecases this confirmed respiratory cultures but in others revealed enrichment by anaerobic organisms or mixed outgrowth of upper respiratory flora and provided quantitative data on relative abundances of bacteria found by culture. Conclusions: Respiratory tract microbial communities in lung trans-plant recipients differ in structure and composition from healthy sub-jects. Outlier analysis can identify specific bacteria replicating in lung. These findings provide novel approaches to address the relationship between microbial communities and transplant outcome and aid in assessing lung infections