title: Impact of the CFTR-potentiator ivacaftor on airway microbiota in cystic fibrosis patients carrying a G551D mutation.
abstract: BACKGROUND
  Airway microbiota composition has been clearly correlated with many pulmonary diseases, and notably with cystic fibrosis (CF), an autosomal genetic disorder caused by mutation in the CF transmembrane conductance regulator (CFTR). Recently, a new molecule, ivacaftor, has been shown to re-establish the functionality of the G551D-mutated CFTR, allowing significant improvement in lung function.
  
  
  OBJECTIVE
  The purpose of this study was to follow the evolution of the airway microbiota in CF patients treated with ivacaftor, using quantitative PCR and pyrosequencing of 16S rRNA amplicons, in order to identify quantitative and qualitative changes in bacterial communities. Three G551D children were followed up longitudinally over a mean period of more than one year covering several months before and after initiation of ivacaftor treatment.
  
  
  RESULTS
  129 operational taxonomy units (OTUs), representing 64 genera, were identified. There was no significant difference in total bacterial load before and after treatment. Comparison of global community composition found no significant changes in microbiota. Two OTUs, however, showed contrasting dynamics: after initiation of ivacaftor, the relative abundance of the anaerobe Porphyromonas 1 increased (p<0.01) and that of Streptococcus 1 (S. mitis group) decreased (p<0.05), possibly in relation to the anti-Gram-positive properties of ivacaftor. The anaerobe Prevotella 2 correlated positively with the pulmonary function test FEV-1 (r=0.73, p<0.05). The study confirmed the presumed positive role of anaerobes in lung function.
  
  
  CONCLUSIONS
  Several airway microbiota components, notably anaerobes (obligate or facultative anaerobes), could be valuable biomarkers of lung function improvement under ivacaftor, and could shed light on the pathophysiology of lung disease in CF patients.
authors: EA 3882-Laboratoire Universitaire de Biodiversité et Ecologie Microbienne, Université de Brest, Brest, France.
authors: Cédric
authors: C
authors: Bernarde
authors: EA 3882-Laboratoire Universitaire de Biodiversité et Ecologie Microbienne, Université de Brest, Brest, France.
authors: Marlène
authors: M
authors: Keravec
authors: EA 3882-Laboratoire Universitaire de Biodiversité et Ecologie Microbienne, Université de Brest, Brest, France.
authors: Jérôme
authors: J
authors: Mounier
authors: EA 3882-Laboratoire Universitaire de Biodiversité et Ecologie Microbienne, Université de Brest, Brest, France.
authors: Stéphanie
authors: S
authors: Gouriou
authors: Centre de Perharidy, CRCM mixte, Roscoff, France.
authors: Gilles
authors: G
authors: Rault
authors: UMR1078, Institut National de la Santé et de la Recherche Médicale, Brest, France; Laboratoire de Génétique Moléculaire, CHRU Brest, Brest, France; Faculté de Médecine et des Sciences de la Santé, Université de Brest, Brest, France; Etablissement Français du Sang-Bretagne, Brest, France.
authors: Claude
authors: C
authors: Férec
authors: EA 3882-Laboratoire Universitaire de Biodiversité et Ecologie Microbienne, Université de Brest, Brest, France.
authors: Georges
authors: G
authors: Barbier
authors: EA 3882-Laboratoire Universitaire de Biodiversité et Ecologie Microbienne, Université de Brest, Brest, France; Département de Bactériologie-Virologie, Hygiène et Parasitologie-Mycologie, CHRU Brest, Brest, France.
authors: Geneviève
authors: G
authors: Héry-Arnaud
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D000627:Aminophenols / Q000627:therapeutic use*; D000693:Anaerobiosis / Q000502:physiology; D015373:Bacterial Typing Techniques; D002648:Child; D065101:Chloride Channel Agonists / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008168:Lung / Q000187:drug effects* / Q000382:microbiology* / Q000503:physiopathology; D064307:Microbiota / Q000235:genetics*; D058990:Molecular Targeted Therapy; D009154:Mutation; D017861:Porphyromonas / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification; D018720:Prevotella / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification; D015363:Quinolones / Q000627:therapeutic use*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012129:Respiratory Function Tests; D013291:Streptococcus / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification; D016896:Treatment Outcome
chemical_list: D000627:Aminophenols; C505032:CFTR protein, human; D065101:Chloride Channel Agonists; D015363:Quinolones; D012336:RNA, Ribosomal, 16S; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor