Microbial Communities of Conducting and Respiratory Zones of Lung-Transplanted Patients

Marie Beaume, Vladimir Lazarevic, Thilo Köhler, Nadia Gaïa, Oriol Manuel, John-David Aubert, Loïc Baerlocher, Laurent Farinelli, Paola Gasche, Jacques Schrenzel, Christian van Delden, the Swiss Transplant Cohort Study, Rita Achermann, Patrizia Amico, John-David Aubert, Philippe Baumann, Guido Beldi, Christian Benden, Christoph Berger, Isabelle Binet, Pierre-Yves Bochud, Elsa Boely, Heiner Bucher, Leo Bühler, Thierry Carell, Emmanuelle Catana, Yves Chalandon, Sabina de Geest, Olivier de Rougemont, Michael Dickenmann, Michel Duchosal, Thomas Fehr, Sylvie Ferrari-Lacraz, Christian Garzoni, Paola G. Soccal, Emiliano Giostra, Déla Golshayan, Daniel Good, Karine Hadaya, Jörg Halter, Dominik Heim, Christoph Hess, Sven Hillinger, Hans H. Hirsch, Cédric Hirzel, Günther Hofbauer, Uyen Huynh-Do, Franz Immer, Richard Klaghofer, Michael Koller, Bettina Laesser, Roger Lehmann, Christian Lovis, Oriol Manuel, Hans-Peter Marti, Pierre Y. Martin, Luca Martinolli, Pascal Meylan, Paul Mohacsi, Isabelle Morard, Philippe Morel, Ulrike Mueller, Nicolas J. Mueller, Helen Mueller-McKenna, Antonia Müller, Thomas Müller, Beat Müllhaupt, David Nadal, Manuel Pascual, Jakob Passweg, Chantal P. Ziegler, Juliane Rick, Eddy Roosnek, Anne Rosselet, Silvia Rothlin, Frank Ruschitzka, Urs Schanz, Stefan Schaub, Christian Seiler, Susanne Stampf, Jürg Steiger, Guido Stirnimann, Guido Toso, Dimitri Tsinalis, Christian Van Delden, Jean-Pierre Venetz, Jean Villard, Madeleine Wick, Markus Wilhelm, Patrick Yerly

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.