Abstract
BackgroundRecent studies suggest that alterations in lung microbiome are associated with occurrence of chronic lung diseases and transplant rejection. To investigate the host-microbiome interactions, we characterized the airway microbiome and metabolome of the allograft (transplanted lung) and native lung of single lung transplant recipients.MethodsBAL was collected from the allograft and native lungs of SLTs and healthy controls. 16S rRNA microbiome analysis was performed on BAL bacterial pellets and supernatant used for metabolome, cytokines and acetylated proline-glycine-proline (Ac-PGP) measurement by liquid chromatography-high-resolution mass spectrometry.ResultsIn our cohort, the allograft airway microbiome was distinct with a significantly higher bacterial burden and relative abundance of genera Acinetobacter & Pseudomonas. Likewise, the expression of the pro-inflammatory cytokine VEGF and the neutrophil chemoattractant matrikine Ac-PGP in the allograft was significantly higher. Airway metabolome distinguished the native lung from the allografts and an increased concentration of sphingosine-like metabolites that negatively correlated with abundance of bacteria from phyla Proteobacteria.ConclusionsAllograft lungs have a distinct microbiome signature, a higher bacterial biomass and an increased Ac-PGP compared to the native lungs in SLTs compared to the native lungs in SLTs. Airway metabolome distinguishes the allografts from native lungs and is associated with distinct microbial communities, suggesting a functional relationship between the local microbiome and metabolome.
Highlights
Recent studies have implicated the lung microbiome in the occurrence of chronic lung diseases such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease, cystic fibrosis and chronic lung allograft dysfunction (CLAD) in lung transplant recipients [1,2,3,4]
Differences between the allograft and native lung microbiome We first determined the bacterial count in Allograft (A), Native (N), normal (H) groups using 16 S quantitative Polymerase chain reaction (PCR)
Bacterial 16S DNA levels reported as log 16S copies/ml of Bronchoalveolar lavage (BAL) were significantly different among the groups (P = 0.02, A 4.15 × 107 vs N 2.0 × 107, P = 0.1, A 4.15 × 107 vs H1.8 × 105, P = 0.04, N vs H, P=NS) and higher in the allograft compared to normal controls (Fig. 1a)
Summary
Recent studies have implicated the lung microbiome in the occurrence of chronic lung diseases such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease, cystic fibrosis and chronic lung allograft dysfunction (CLAD) in lung transplant recipients [1,2,3,4]. Delineation of the microbiome signatures and taxonomic profiles of bacterial communities in various disease states is Sharma et al Respiratory Research (2020) 21:104 an important first step but does not directly provide an insight into bacteriome-allograft-host interaction. A better understanding of these metabolic shifts associated with a specific infection can improve our understanding of disease pathophysiology through the identification of by-products of host and microbial metabolism, while providing vital information about the unique metabolites produced with these everchanging interactions [11]. Specific metabolome pathways have been identified in lung transplant recipients with CLAD [15], though further investigations are needed to delineate its relevance to CLAD pathobiology. Identification and correlation of novel metabolome profiles associated with specific pathological microbiome signatures may help guide personalized treatment of host disease states [16]. To investigate the host-microbiome interactions, we characterized the airway microbiome and metabolome of the allograft (transplanted lung) and native lung of single lung transplant recipients
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