The Lung Microbiome in CLAD is Characterized by Higher Bacterial Burden and Increased Abundance of Oral Flora

PurposeChronic lung allograft dysfunction (CLAD) is the leading long-term cause of mortality after transplant. The microbiome in healthy transplant recipients predicts subsequent development CLAD, but whether bacteria differ between CLAD and allografts unknown.MethodsWe performed a case control study using biorepository acellular bronchoalveolar lavage (BAL) fluid. Controls were specimens collected from asymptomatic patients undergoing surveillance bronchoscopy one-year post-transplant; cases within 90 days onset. Bacterial DNA burden was measured BioRad QX200 Droplet Digital PCR 16S rRNA gene sequencing Illumina MiSeq.ResultsWe identified 131 which met criteria for use as CLAD-free controls 78 critieria cases. at vs. characterized by higher bacterial (median [IQR]16S copies per mL 4991 [2889-13075] 3561 [2426-8131], p=0.028, Panel A). There significant overall community composition differences both PERMANOVA (p=0.032) mvabund, model-based approach to analysis multivariable abundance data (p=0.014, B). As shown biplot analysis, communities with had relatively more oral flora than controls; although no individual taxa responsible these differences. Twenty-two BAL available time points. In paired comparisons, there intra-patient burden, diversity or onset samples.ConclusionThe increased predominance commonly found upper respiratory tract. Chronic unknown. We MiSeq. samples.