Extended-culture and culture-independent molecular analysis of the airway microbiota in cystic fibrosis following CFTR modulation with ivacaftor
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Accepted Version
Supplementary Materials
Date
2021-09-21
Authors
Einarsson, Gisli G.
Ronan, Nicola J.
Mooney, Denver
McGettigan, Clodagh
Mullane, David
NiChroinin, Muireann
Shanahan, Fergus
Murphy, Desmond M.
McCarthy, Mairead
McCarthy, Yvonne
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier B.V.
Published Version
Abstract
Background: 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.
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Keywords
Respiratory microbiome , CFTR modulation , Ivacaftor
Citation
Einarsson, 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.2020.12.023