Cystic Fibrosis Lung Transplant Microbiome (16S)

Introduction: Lung transplantation is commonly required for end-stage lung disease in cystic fibrosis (CF). Chronic lung allograft dysfunction (CLAD) is the main barrier to long-term allograft survival and microbial factors have been implicated in CLAD development. However, studies have not specifically investigated CF patients despite the unique microbe-rich nature of the CF respiratory tract.Methods: Longitudinal cohort study of 23 CF lung transplantation recipients. Lavage was collected from donor lungs and recipients serially for one-year post-transplantation. Patients were followed for a median of 4.9 years. This was complemented by a case-control study of 8 CF patients sampled at incident CLAD and 23 CF non-CLAD controls. Lung bacteria were investigated by 16S rRNA gene sequencing, bacterial burden quantified by 16S qPCR, and immune mediators analyzed by multiplex assay.Results: Eight longitudinal cohort patients developed CLAD during follow-up. Over the first-year post-transplantation they had significantly lower lung bacterial burden, lower relative abundances of classic CF lung microbiota, and higher relative abundances of background taxa, than those remaining CLAD-free. Immune mediators in lung were highly correlated and significantly lower in patients who developed CLAD than CLAD-free patients. In contrast, incident CLAD patients exhibited elevated lung immune mediators but no bacterial microbiome differences.Conclusions: Low bacterial content and low immune mediators in lung during the first-year post-transplantation are seen in patients with CF who develop CLAD, whereas elevated immune mediators but not lung bacterial microbiome differences are present at CLAD onset. In CF patients, airway bacteria early after transplantation may protect against CLAD development