The Pulmonary Microbiome After Lung Transplantation Is Associated With Gastroesophageal Reflux Disease, Inflammation, And Allograft Dysfunction

Purpose The pulmonary microbiome modulates the immune milieu in the lung allograft and is in turn influenced by gastroesophageal reflux disease (GERD). Although GERD has been linked to a higher risk of chronic lung allograft dysfunction (CLAD), the underlying role of the allograft microbiome is unknown. We assessed the relationships between the post-transplant pulmonary microbiome, GERD, inflammation, and allograft dysfunction. Methods 24 GERD and 51 no-GERD patients, defined by pH-impedance probe, had bronchoalveolar lavage (BAL) obtained at 3, 6, 9, and 12 months post-transplant. A separate cohort of 18 patients who underwent Nissen fundoplication for GERD within the first year post-transplant had BAL obtained before and after surgery. BAL were analysed for microbial communities and inflammatory cytokines using 16S rRNA sequencing and immunoassays, respectively. Results Hierarchical clustering of all GERD and no-GERD samples by Bray-Curtis dissimilarity identified three distinct community state types (CST) (Figure A). CST1 was positively associated with GERD and enriched in Prevotella and Veillonella. CST2 was negatively associated with GERD and enriched in Streptococcus. CST3 was independent of GERD and enriched in Pseudomonas and Staphylococcus. Compared to other CSTs, CST3 was associated with a greater proportion of patients with BAL inflammation, concurrent acute decline in lung function at 3 months, and earlier CLAD onset. Patients with the greatest decrease in BAL inflammation post-Nissen also had decreases in bacterial load and density of Prevotella (Figure B). Conclusion Pulmonary microbiota after lung transplantation cluster into three CSTs which differ by their associations with GERD. CST3 may represent a GERD-independent state of microbial dysbiosis which promotes inflammation and allograft rejection. Anti-GERD surgery appears to decrease GERD-associated microbiota.