Abstract

Background: Lung transplantation (LT) is a recognized treatment for end-stage pulmonary disease. Bacteria from the recipient nasopharynx seed the new lungs leading to infections and allograft damage. Understanding the characteristics and topological variations of the microbiota may be important to apprehend the pathophysiology of allograft dysfunction.Objectives: To examine the characteristics and relationship of bacterial compositions between conducting and respiratory zones of the allograft.Methods: We performed 16S rRNA gene sequencing on bronchial aspirates (BAs) and bronchoalveolar lavages (BALs) collected in pairs in 19 patients at several time-points post-LT.Results: The respiratory zone was characterized independently of the time post-LT by a higher bacterial richness than the conducting zone (p = 0.041). The phyla Firmicutes and Proteobacteria dominated both sampling zones, with an inverse correlation between these two phyla (Spearman r = –0.830). Samples of the same pair, as well as pairs from the same individual clustered together (Pseudo-F = 3.8652, p < 0.01). Microbiota of BA and BAL were more closely related in samples from the same patient than each sample type across different patients, with variation in community structure being mainly inter-individual (p < 0.01). Both number of antibiotics administered (p < 0.01) and time interval post-LT (p < 0.01) contributed to the variation in global microbiota structure. Longitudinal analysis of BA–BAL pairs of two patients showed dynamic wave like fluctuations of the microbiota.Conclusions: Our results show that post-transplant respiratory zones harbor higher bacterial richness, but overall similar bacterial profiles as compared to conductive zones. They further support an individual microbial signature following LT.

Highlights

  • Lung transplantation (LT) is the sole therapeutic intervention for patients with end-stage pulmonary disease

  • bronchoalveolar lavages (BALs) fluid was obtained by aspiration of 10–20 ml distal respiratory secretions, representing a more homogenous sample from a distal respiratory zone. 1 mL of each airway sample was immediately stored at −80◦C after sampling

  • Thirty-eight paired bronchial aspirates (BAs) and BAL samples were obtained from 19 lung-transplant recipients at different time-points post-LT (Table 1; Figure 1B)

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Summary

Introduction

Lung transplantation (LT) is the sole therapeutic intervention for patients with end-stage pulmonary disease. The outcome after LT is worse compared to other solid organ transplantations, with a median survival of 5.7 years post-LT (Yusen et al, 2015). Mortality during the 1st year post-LT is mainly due to infections, whereas late mortality is linked to chronic rejection, notably the bronchiolitis obliterans syndrome (BOS). Cystic fibrosis (CF) lung-transplant recipients are at high risk of infection due to chronic pre-transplant colonization with microorganisms including Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa, the latter being the most frequent pathogen in adult CF-patients (Cystic Fibrosis Foundation, 2011). Preventing infections is one of the major challenges to increase allograft survival and to improve outcome after LT. Lung transplantation (LT) is a recognized treatment for end-stage pulmonary disease. Understanding the characteristics and topological variations of the microbiota may be important to apprehend the pathophysiology of allograft dysfunction

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