Late Breaking Abstract - Disturbance Of The Core Microbiota In Transplanted Lung Associates With Sub- Or Excessive Control Of Host Immunity

Introduction: Low density bacterial communities reside in the lower airways, however the importance of their stability for complication-free survival after lung transplantion (Tx) is poorly understood. Aims:i) To identify the most common and abundant members of the bacterial lung microbiota post-Tx, and ii) to explore whether disruption of this core community is linked to clinical complications. Methods: We prospectively analyzed 234 serial bronchoalveolar lavage (BAL) samples from 64 recipients up to 49 months post-Tx, using 16S quantification and sequencing. Unsupervised clustering was used to differentiate bacterial communities. Cell differentials were obtained for paired BAL and blood samples. Post-Tx clinical complications were sought from patient charts. Results: The most common and abundant operational taxonomic units, mapping to the genera Prevotella, Streptococcus and Veillonella, were linked to a single cluster that identified the core lung microbiota. We further observed two divergent bacterial communities linked to contrasting clinical pictures. Compared with the core, median differences in the first sample set were a 46-fold lower bacterial load, 2.7-fold higher blood lymphocyte counts, and a 3.3-fold higher rate of either acute rejection, chronic lung allograft dysfunction or presence of donor-specific antibodies, while those in the second set were a 2.6-fold lower diversity, 4-fold higher BAL neutrophil counts, and a 3.3-fold higher infection rate. Conclusions: Complication-free survival post-lung Tx is tied to a stable core microbiota, the disruption of which is related to sub-control (rejection) or excessive control (infection) of host immunity.