Lung allograft microbiome association with gastroesophageal reflux, inflammation, and allograft dysfunction

RATIONALE: It remains unclear how gastroesophageal reflux disease (GERD) affects allograft microbial community composition in lung transplant recipients, and its impact on lung allograft inflammation and function. OBJECTIVES: Our objective was to compare the allograft microbiota in lung transplant recipients with or without clinically diagnosed GERD in the first post-transplant year, and assess associations between GERD, allograft microbiota, inflammation and acute and chronic lung allograft dysfunction (ALAD/CLAD). METHODS: 268 bronchoalveolar lavage samples were collected from 75 lung transplant recipients at a single transplant centre every 3 months post-transplant for 1 year. Ten transplant recipients from a separate transplant centre provided samples pre/post-anti-reflux Nissen fundoplication surgery. Microbial community composition and density were measured using 16S rRNA gene sequencing and qPCR, respectively and inflammatory markers and bile acids were quantified. MEASUREMENTS AND MAIN RESULTS: We observed a range of allograft community composition with three discernible types (labelled community state types, CSTs 1-3). Transplant recipients with GERD were more likely to have CST1, characterized by high bacterial density and relative abundance of the oropharyngeal colonizing genera Prevotella and Veillonella. GERD was associated with more frequent transitions to CST1. CST1 was associated with lower inflammatory cytokine levels than pathogen-dominated CST3 across the range of microbial densities observed. Cox proportional hazard models revealed associations between CST3 and development of ALAD/CLAD. Nissen fundoplication decreased bacterial load and pro-inflammatory cytokines. CONCLUSION: GERD was associated with a high bacterial density, Prevotella- and Veillonella-dominated CST1. CST3, but not CST1 or GERD, was associated with inflammation and early development of ALAD/CLAD. Nissen fundoplication was associated with reduction in microbial density in BALF samples, especially the CST1-specific genus, Prevotella. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).