Lung microbiota predict invasive pulmonary aspergillosis and its outcome in immunocompromised patients

Abstract Rationale Recent studies have revealed that the lung microbiota of critically ill patients is altered and predicts clinical outcomes. The incidence of invasive fungal infections, namely, invasive pulmonary aspergillosis (IPA), in immunocompromised patients is increasing, but the clinical si...

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Authors: Hérivaux, Anaïs, Willis, Jesse R, Mercier, Toine, Lagrou, Katrien, Gonçalves, Samuel M, Maertens, Johan, Carvalho, Agostinho, Gabaldon, Toni, Cunha, Cristina
Format: article
Publication Date:2021
Country:España
Institution:Universitat Politècnica de Catalunya (UPC)
Repository:UPCommons. Portal del coneixement obert de la UPC
Language:English
OAI Identifier:oai:upcommons.upc.edu:2117/355905
Online Access:https://hdl.handle.net/2117/355905
https://dx.doi.org/10.1136/thoraxjnl-2020-216179
Access Level:Open access
Keyword:DNA
Lung microbiota
Pulmonary aspergillosis
IPA
ADN
Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
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network_name_str España
repository_id_str
dc.title.none.fl_str_mv Lung microbiota predict invasive pulmonary aspergillosis and its outcome in immunocompromised patients
title Lung microbiota predict invasive pulmonary aspergillosis and its outcome in immunocompromised patients
spellingShingle Lung microbiota predict invasive pulmonary aspergillosis and its outcome in immunocompromised patients
Hérivaux, Anaïs
DNA
Lung microbiota
Pulmonary aspergillosis
IPA
ADN
Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
title_short Lung microbiota predict invasive pulmonary aspergillosis and its outcome in immunocompromised patients
title_full Lung microbiota predict invasive pulmonary aspergillosis and its outcome in immunocompromised patients
title_fullStr Lung microbiota predict invasive pulmonary aspergillosis and its outcome in immunocompromised patients
title_full_unstemmed Lung microbiota predict invasive pulmonary aspergillosis and its outcome in immunocompromised patients
title_sort Lung microbiota predict invasive pulmonary aspergillosis and its outcome in immunocompromised patients
dc.creator.none.fl_str_mv Hérivaux, Anaïs
Willis, Jesse R
Mercier, Toine
Lagrou, Katrien
Gonçalves, Samuel M
Maertens, Johan
Carvalho, Agostinho
Gabaldon, Toni
Cunha, Cristina
author Hérivaux, Anaïs
author_facet Hérivaux, Anaïs
Willis, Jesse R
Mercier, Toine
Lagrou, Katrien
Gonçalves, Samuel M
Maertens, Johan
Carvalho, Agostinho
Gabaldon, Toni
Cunha, Cristina
author_role author
author2 Willis, Jesse R
Mercier, Toine
Lagrou, Katrien
Gonçalves, Samuel M
Maertens, Johan
Carvalho, Agostinho
Gabaldon, Toni
Cunha, Cristina
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DNA
Lung microbiota
Pulmonary aspergillosis
IPA
ADN
Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
topic DNA
Lung microbiota
Pulmonary aspergillosis
IPA
ADN
Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
description Abstract Rationale Recent studies have revealed that the lung microbiota of critically ill patients is altered and predicts clinical outcomes. The incidence of invasive fungal infections, namely, invasive pulmonary aspergillosis (IPA), in immunocompromised patients is increasing, but the clinical significance of variations in lung bacterial communities is unknown. Objectives To define the contribution of the lung microbiota to the development and course of IPA. Methods and measurements We performed an observational cohort study to characterise the lung microbiota in 104 immunocompromised patients using bacterial 16S ribosomal RNA gene sequencing on bronchoalveolar lavage samples sampled on clinical suspicion of infection. Associations between lung dysbiosis in IPA and pulmonary immunity were evaluated by quantifying alveolar cytokines and chemokines and immune cells. The contribution of microbial signatures to patient outcome was assessed by estimating overall survival. Main results Patients diagnosed with IPA displayed a decreased alpha diversity, driven by a markedly increased abundance of the Staphylococcus, Escherichia, Paraclostridium and Finegoldia genera and a decreased proportion of the Prevotella and Veillonella genera. The overall composition of the lung microbiome was influenced by the neutrophil counts and associated with differential levels of alveolar cytokines. Importantly, the degree of bacterial diversity at the onset of IPA predicted the survival of infected patients. Conclusions Our results reveal the lung microbiota as an understudied source of clinical variation in patients at risk of IPA and highlight its potential as a diagnostic and therapeutic target in the context of respiratory fungal diseases.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01
2021
2021-11-09
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/2117/355905
https://dx.doi.org/10.1136/thoraxjnl-2020-216179
url https://hdl.handle.net/2117/355905
https://dx.doi.org/10.1136/thoraxjnl-2020-216179
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://doi.org/10.13039/100010661 Horizon 2020 Framework Programme 724173 Reticulate evolution: patterns and impacts of non-vertical inheritance in eukaryotic genomes.
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial 3.0 Spain
http://creativecommons.org/licenses/by-nc/3.0/es/
Attribution-NonCommercial 3.0 Spain
https://creativecommons.org/licenses/by-nc/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial 3.0 Spain
http://creativecommons.org/licenses/by-nc/3.0/es/
https://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BMJ Publishing Group
publisher.none.fl_str_mv BMJ Publishing Group
dc.source.none.fl_str_mv reponame:UPCommons. Portal del coneixement obert de la UPC
instname:Universitat Politècnica de Catalunya (UPC)
instname_str Universitat Politècnica de Catalunya (UPC)
reponame_str UPCommons. Portal del coneixement obert de la UPC
collection UPCommons. Portal del coneixement obert de la UPC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Lung microbiota predict invasive pulmonary aspergillosis and its outcome in immunocompromised patientsHérivaux, AnaïsWillis, Jesse RMercier, ToineLagrou, KatrienGonçalves, Samuel MMaertens, JohanCarvalho, AgostinhoGabaldon, ToniCunha, CristinaDNALung microbiotaPulmonary aspergillosisIPAADNÀrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::BioinformàticaAbstract Rationale Recent studies have revealed that the lung microbiota of critically ill patients is altered and predicts clinical outcomes. The incidence of invasive fungal infections, namely, invasive pulmonary aspergillosis (IPA), in immunocompromised patients is increasing, but the clinical significance of variations in lung bacterial communities is unknown. Objectives To define the contribution of the lung microbiota to the development and course of IPA. Methods and measurements We performed an observational cohort study to characterise the lung microbiota in 104 immunocompromised patients using bacterial 16S ribosomal RNA gene sequencing on bronchoalveolar lavage samples sampled on clinical suspicion of infection. Associations between lung dysbiosis in IPA and pulmonary immunity were evaluated by quantifying alveolar cytokines and chemokines and immune cells. The contribution of microbial signatures to patient outcome was assessed by estimating overall survival. Main results Patients diagnosed with IPA displayed a decreased alpha diversity, driven by a markedly increased abundance of the Staphylococcus, Escherichia, Paraclostridium and Finegoldia genera and a decreased proportion of the Prevotella and Veillonella genera. The overall composition of the lung microbiome was influenced by the neutrophil counts and associated with differential levels of alveolar cytokines. Importantly, the degree of bacterial diversity at the onset of IPA predicted the survival of infected patients. Conclusions Our results reveal the lung microbiota as an understudied source of clinical variation in patients at risk of IPA and highlight its potential as a diagnostic and therapeutic target in the context of respiratory fungal diseases.This work was supported by the Fundação para a Ciência e a Tecnologia (FCT) (PTDC/SAU-SER/29635/2017 to CC and PTDC/MED-GEN/28778/2017 to AC). Additional support was provided by FCT (UIDB/50026/2020 and UIDP/50026/2020); the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023); the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement number 847507 (to AC); and the “la Caixa” Foundation (ID 100010434) and FCT under the agreement LCF/PR/HR17/52190003 (to AC). Individual support was provided by FCT (SFRH/BD/136814/2018 to SMG, CEECIND/03628/2017 to AC and CEECIND/04058/2018 to CC). The TG group acknowledges support from the Spanish Ministry of Science and Innovation for grant PGC2018-099921-B-I00, cofounded by the ERDF, the CERCA Programme/Generalitat de Catalunya, the Catalan Research Agency (AGAUR) SGR423, the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement ERC-2016-724173 and an INB Grant (PT17/0009/0023—ISCIII-SGEFI/ERDF).Peer ReviewedBMJ Publishing Group20212021-01-0120212021-11-09journal articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2117/355905https://dx.doi.org/10.1136/thoraxjnl-2020-216179reponame:UPCommons. Portal del coneixement obert de la UPCinstname:Universitat Politècnica de Catalunya (UPC)InglésengEuropean Commission http://doi.org/10.13039/100010661 Horizon 2020 Framework Programme 724173 Reticulate evolution: patterns and impacts of non-vertical inheritance in eukaryotic genomes.open accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial 3.0 Spainhttp://creativecommons.org/licenses/by-nc/3.0/es/Attribution-NonCommercial 3.0 Spainhttps://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:upcommons.upc.edu:2117/3559052026-05-27T15:37:01Z
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