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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 re...

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Autores principales: Schneeberger, Pierre H. H., Zhang, Chen Yang Kevin, Santilli, Jessica, Chen, Bo, Xu, Wei, Lee, Youngho, Wijesinha, Zonelle, Reguera-Nuñez, Elaine, Yee, Noelle, Ahmed, Musawir, Boonstra, Kristen, Ramendra, Rayoun, Frankel, Courtney W., Palmer, Scott M., Todd, Jamie L., Martinu, Tereza, Coburn, Bryan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Thoracic Society 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9757088/
https://www.ncbi.nlm.nih.gov/pubmed/35876129
http://dx.doi.org/10.1164/rccm.202110-2413OC
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author Schneeberger, Pierre H. H.
Zhang, Chen Yang Kevin
Santilli, Jessica
Chen, Bo
Xu, Wei
Lee, Youngho
Wijesinha, Zonelle
Reguera-Nuñez, Elaine
Yee, Noelle
Ahmed, Musawir
Boonstra, Kristen
Ramendra, Rayoun
Frankel, Courtney W.
Palmer, Scott M.
Todd, Jamie L.
Martinu, Tereza
Coburn, Bryan
author_facet Schneeberger, Pierre H. H.
Zhang, Chen Yang Kevin
Santilli, Jessica
Chen, Bo
Xu, Wei
Lee, Youngho
Wijesinha, Zonelle
Reguera-Nuñez, Elaine
Yee, Noelle
Ahmed, Musawir
Boonstra, Kristen
Ramendra, Rayoun
Frankel, Courtney W.
Palmer, Scott M.
Todd, Jamie L.
Martinu, Tereza
Coburn, Bryan
author_sort Schneeberger, Pierre H. H.
collection PubMed
description 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 year after transplant and assess associations between GERD, allograft microbiota, inflammation, and acute and chronic lung allograft dysfunction (ALAD and CLAD). METHODS: A total of 268 BAL samples were collected from 75 lung transplant recipients at a single transplant center every 3 months after transplant for 1 year. Ten transplant recipients from a separate transplant center provided samples before and after antireflux Nissen fundoplication surgery. Microbial community composition and density were measured using 16S ribosomal RNA gene sequencing and quantitative polymerase chain reaction, 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 (labeled 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 concentrations than pathogen-dominated CST3 across the range of microbial densities observed. Cox proportional hazard models revealed associations between CST3 and the development of ALAD/CLAD. Nissen fundoplication decreased bacterial load and proinflammatory cytokines. CONCLUSIONS: 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 and CLAD. Nissen fundoplication was associated with a reduction in microbial density in BAL fluid samples, especially the CST1-specific genus, Prevotella.
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spelling pubmed-97570882022-12-19 Lung Allograft Microbiome Association with Gastroesophageal Reflux, Inflammation, and Allograft Dysfunction Schneeberger, Pierre H. H. Zhang, Chen Yang Kevin Santilli, Jessica Chen, Bo Xu, Wei Lee, Youngho Wijesinha, Zonelle Reguera-Nuñez, Elaine Yee, Noelle Ahmed, Musawir Boonstra, Kristen Ramendra, Rayoun Frankel, Courtney W. Palmer, Scott M. Todd, Jamie L. Martinu, Tereza Coburn, Bryan Am J Respir Crit Care Med Original Articles 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 year after transplant and assess associations between GERD, allograft microbiota, inflammation, and acute and chronic lung allograft dysfunction (ALAD and CLAD). METHODS: A total of 268 BAL samples were collected from 75 lung transplant recipients at a single transplant center every 3 months after transplant for 1 year. Ten transplant recipients from a separate transplant center provided samples before and after antireflux Nissen fundoplication surgery. Microbial community composition and density were measured using 16S ribosomal RNA gene sequencing and quantitative polymerase chain reaction, 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 (labeled 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 concentrations than pathogen-dominated CST3 across the range of microbial densities observed. Cox proportional hazard models revealed associations between CST3 and the development of ALAD/CLAD. Nissen fundoplication decreased bacterial load and proinflammatory cytokines. CONCLUSIONS: 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 and CLAD. Nissen fundoplication was associated with a reduction in microbial density in BAL fluid samples, especially the CST1-specific genus, Prevotella. American Thoracic Society 2022-07-23 /pmc/articles/PMC9757088/ /pubmed/35876129 http://dx.doi.org/10.1164/rccm.202110-2413OC Text en Copyright © 2022 by the American Thoracic Society https://creativecommons.org/licenses/by-nc-nd/4.0/This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . For commercial usage and reprints, please e-mail Diane Gern (dgern@thoracic.org).
spellingShingle Original Articles
Schneeberger, Pierre H. H.
Zhang, Chen Yang Kevin
Santilli, Jessica
Chen, Bo
Xu, Wei
Lee, Youngho
Wijesinha, Zonelle
Reguera-Nuñez, Elaine
Yee, Noelle
Ahmed, Musawir
Boonstra, Kristen
Ramendra, Rayoun
Frankel, Courtney W.
Palmer, Scott M.
Todd, Jamie L.
Martinu, Tereza
Coburn, Bryan
Lung Allograft Microbiome Association with Gastroesophageal Reflux, Inflammation, and Allograft Dysfunction
title Lung Allograft Microbiome Association with Gastroesophageal Reflux, Inflammation, and Allograft Dysfunction
title_full Lung Allograft Microbiome Association with Gastroesophageal Reflux, Inflammation, and Allograft Dysfunction
title_fullStr Lung Allograft Microbiome Association with Gastroesophageal Reflux, Inflammation, and Allograft Dysfunction
title_full_unstemmed Lung Allograft Microbiome Association with Gastroesophageal Reflux, Inflammation, and Allograft Dysfunction
title_short Lung Allograft Microbiome Association with Gastroesophageal Reflux, Inflammation, and Allograft Dysfunction
title_sort lung allograft microbiome association with gastroesophageal reflux, inflammation, and allograft dysfunction
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9757088/
https://www.ncbi.nlm.nih.gov/pubmed/35876129
http://dx.doi.org/10.1164/rccm.202110-2413OC
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