ENAGenomicsQueen's University Belfast, Belfast, Northern Ireland, UKQUBhttps://www.ebi.ac.uk/ena/browser/view/PRJEB37510Background: 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.ENACystic fibrosis NOS, Microbial Community Composition, CFTR|MRP, determination, susceptibility to chronic infection by, Meconium obstruction of intestine in mucoviscidosis, dJ760C5.1, Pancreas Fibrocystic Diseases, 4-bis(1, Human, Background, Cultural, 3-quinolinecarboxamide, cystic fibrosis with other manifestations (disorder), Abcc7, channel-conductance-controlling ATPase activity, 1-dimethylethyl)-5-hydroxyphenyl)-1, cystic fibrosis lung disease, TNR-CFTR, modifier of, Meconium ileus in cystic fibrosis (disorder), Backgrounds, Pulmonary, CFTR, ethnicity, cystic fibrosis with meconium ileus, airways, Cystic Fibrosis of Pancreas, cystic fibrosis with other manifestations, Microbial Community Structure, segment of tracheobronchial tree, Cultural Relativisms, cystic fibrosis with combined manifestations, 4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1, cystic fibrosis with gastrointestinal manifestations, 1-dimethylethyl)-5-hydroxyphenyl)-4-oxo-1, Fibrocystic disease, CF, Cystic Fibrosis, MRP7, VX-770, Microbial Community Structures, Customs, Pulmonary Cystic Fibrosis, ivacaftor., culture, cystic fibrosis transmembrane conductance regulator, Human Microbiome, pseudomonas aeruginosa, Community Composition, CFTR/MRP, cAMP-dependent chloride channel, 4-dihydroquinoline-3-carboxamide, Mucoviscidosis, Cystic fibrosis NOS (disorder), ABC35, Cultural Backgrounds, Microbial, CF - Cystic fibrosis, cystic fibrosis with pulmonary manifestations, ABCC7, Cultural Background, Cultures, tracheobronchial tree segment, chemical analysis, CYSTIC FIBROS W/O ILEUS, ivacaftorum, ATP-binding cassette sub-family C member 7, Channel conductance-controlling ATPase, Pancreatic, Fibrosis, Microbial Communities, Microbiome, in cystic fibrosis, Cystic fibrosis (disorder), Pancreatic Cystic Fibrosis, Microbiomes, Cultural Beliefs, Microbial Community Compositions, Microbial Community, N-(2, Community Structure, Cystic fibrosis without mention of meconium ileus, cystic fibrosis, cystic fibrosis with meconium ileus (disorder), respiratory conducting tube, Fibrocystic Disease of Pancreas, Composition, Cystic, airway, Kalydeco, mucoviscidosis, Pancreas Fibrocystic Disease, Relativisms, Microbiotas, 3.6.3.49, assay, Relativism, Cultural Relativism, AW495489, Human Microbiomes, cystic fibrosis with pulmonary manifestations (disorder), Community, 4-dihydro-4-oxo-Cystic fibrosis NOS, Microbial Community Composition, CFTR|MRP, determination, susceptibility to chronic infection by, Meconium obstruction of intestine in mucoviscidosis, dJ760C5.1, Pancreas Fibrocystic Diseases, 4-bis(1, Human, Background, Cultural, 3-quinolinecarboxamide, cystic fibrosis with other manifestations (disorder), Abcc7, channel-conductance-controlling ATPase activity, 1-dimethylethyl)-5-hydroxyphenyl)-1, cystic fibrosis lung disease, TNR-CFTR, modifier of, Meconium ileus in cystic fibrosis (disorder), Backgrounds, Pulmonary, CFTR, ethnicity, cystic fibrosis with meconium ileus, airways, Cystic Fibrosis of Pancreas, cystic fibrosis with other manifestations, Microbial Community Structure, segment of tracheobronchial tree, Cultural Relativisms, cystic fibrosis with combined manifestations, 4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1, cystic fibrosis with gastrointestinal manifestations, 1-dimethylethyl)-5-hydroxyphenyl)-4-oxo-1, Fibrocystic disease, CF, Cystic Fibrosis, MRP7, VX-770, Microbial Community Structures, Customs, Pulmonary Cystic Fibrosis, ivacaftor., culture, cystic fibrosis transmembrane conductance regulator, Human Microbiome, pseudomonas aeruginosa, Community Composition, CFTR/MRP, cAMP-dependent chloride channel, 4-dihydroquinoline-3-carboxamide, Mucoviscidosis, Cystic fibrosis NOS (disorder), ABC35, Cultural Backgrounds, Microbial, CF - Cystic fibrosis, cystic fibrosis with pulmonary manifestations, ABCC7, Cultural Background, Cultures, tracheobronchial tree segment, chemical analysis, CYSTIC FIBROS W/O ILEUS, ivacaftorum, ATP-binding cassette sub-family C member 7, Channel conductance-controlling ATPase, Pancreatic, Fibrosis, Microbial Communities, Microbiome, in cystic fibrosis, Cystic fibrosis (disorder), Pancreatic Cystic Fibrosis, Microbiomes, Cultural Beliefs, Microbial Community Compositions, Microbial Community, N-(2, Community Structure, Cystic fibrosis without mention of meconium ileus, cystic fibrosis, cystic fibrosis with meconium ileus (disorder), respiratory conducting tube, Fibrocystic Disease of Pancreas, Composition, Cystic, airway, Kalydeco, mucoviscidosis, Pancreas Fibrocystic Disease, Relativisms, Microbiotas, 3.6.3.49, assay, Relativism, Cultural Relativism, AW495489, Human Microbiomes, cystic fibrosis with pulmonary manifestations (disorder), Community, 4-dihydro-4-oxo-falseExtended-culture and culture-independent molecular analysis of the airway microbiota in cystic fibrosis following CFTR modulation with ivacaftor.Extended-culture and culture-independent molecular analysis of the airway microbiota in cystic fibrosis following CFTR modulation with ivacaftor.2020-03-272020-08-27PRJEB37510