Extended-culture and culture-independent molecular analysis of the airway microbiota in cystic fibrosis following CFTR modulation with ivacaftor

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dc.contributor.authorEinarsson, Gisli G.en
dc.contributor.authorRonan, Nicola J.en
dc.contributor.authorMooney, Denveren
dc.contributor.authorMcGettigan, Clodaghen
dc.contributor.authorMullane, Daviden
dc.contributor.authorNiChroinin, Muireannen
dc.contributor.authorShanahan, Fergusen
dc.contributor.authorMurphy, Desmond M.en
dc.contributor.authorMcCarthy, Maireaden
dc.contributor.authorMcCarthy, Yvonneen
dc.contributor.authorEustace, Joseph A.en
dc.contributor.authorGilpin, Deirdre F.en
dc.contributor.authorElborn, J. Stuarten
dc.contributor.authorPlant, Barry J.en
dc.contributor.authorTunney, Michael M.en
dc.contributor.funderSeventh Framework Programmeen
dc.date.accessioned2023-05-05T11:20:34Z
dc.date.available2023-05-05T11:20:34Z
dc.date.issued2021-09-21en
dc.description.abstractBackground: Treatment with Ivacaftor provides a significant clinical benefit in people with cystic fibrosis (PWCF) with the class III G551D-CFTR mutation. This study determined the effect of CFTR modulation with ivacaftor on the lung microbiota in PWCF. Methods: Using both extended-culture and culture-independent molecular methods, we analysed the lower airway microbiota of 14 PWCF, prior to commencing ivacaftor treatment and at the last available visit within the following year. We determined total bacterial and Pseudomonas aeruginosa densities by both culture and qPCR, assessed ecological parameters and community structure and compared these with biomarkers of inflammation and clinical outcomes. Results: Significant improvement in FEV1, BMI, sweat chloride and levels of circulating inflammatory biomarkers were observed POST-ivacaftor treatment. Extended-culture demonstrated a higher density of strict anaerobic bacteria (p = 0.024), richness (p = 1.59*10−4) and diversity (p = 0.003) POST-treatment. No significant difference in fold change was observed by qPCR for either total bacterial 16S rRNA copy number or P. aeruginosa density for oprL copy number with treatment. Culture-independent (MiSeq) analysis revealed a significant increase in richness (p = 0.03) and a trend towards increased diversity (p = 0.07). Moreover, improvement in lung function, richness and diversity displayed an inverse correlation with the main markers of inflammation (p < 0.05). Conclusions: Following treatment with ivacaftor, significant improvements in clinical parameters were seen. Despite modest changes in overall microbial community composition, there was a shift towards a bacterial ecology associated with less severe CF lung disease. Furthermore, a significant correlation was observed between richness and diversity and levels of circulating inflammatory markers.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationEinarsson, G. G., Ronan, N. J., Mooney, D., McGettigan, C., Mullane, D., NiChroinin, M., Shanahan, F., Murphy, D. M., McCarthy, M., McCarthy, Y. and Eustace, J. A. (2021) 'Extended-culture and culture-independent molecular analysis of the airway microbiota in cystic fibrosis following CFTR modulation with ivacaftor', Journal of Cystic Fibrosis, 20(5), pp.747-753. doi: 10.1016/j.jcf.2020.12.023en
dc.identifier.doi10.1016/j.jcf.2020.12.023en
dc.identifier.endpage753en
dc.identifier.issn1569-1993en
dc.identifier.issued5en
dc.identifier.journaltitleJournal of Cystic Fibrosisen
dc.identifier.startpage747en
dc.identifier.urihttps://hdl.handle.net/10468/14438
dc.identifier.volume20en
dc.language.isoenen
dc.publisherElsevier B.V.en
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::HEALTH/603038/EU/Cystic Fibrosis Microbiome-determined Antibiotic Therapy Trial in Exacerbations: Results Stratified./CFMATTERSen
dc.rights© 2021, European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 license.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectRespiratory microbiomeen
dc.subjectCFTR modulationen
dc.subjectIvacaftoren
dc.titleExtended-culture and culture-independent molecular analysis of the airway microbiota in cystic fibrosis following CFTR modulation with ivacaftoren
dc.typeArticle (peer-reviewed)en
oaire.citation.issue5en
oaire.citation.volume20en
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