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Impact of the CFTR-potentiator ivacaftor on airway microbiota in cystic fibrosis patients carrying a G551D mutation.

Bernarde C, Keravec M, Mounier J, Gouriou S, Rault G, Férec C, Barbier G, Héry-Arnaud G - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: EA 3882-Laboratoire Universitaire de Biodiversité et Ecologie Microbienne, Université de Brest, Brest, France.

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 and methods: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Relative abundance (RA) of OTUs belonging to the major core microbiota.A) RA of OTUs for the three patients (GM, PM, and RM) highlighted that each individual harbored his or her own microbiota, even if several genera were shared. B) RA of OTUs before ivacaftor treatment (BT) and after the beginning of ivacaftor treatment (AT) for each patient. RA of Streptococcus 1 showed a tendency to decrease from BT to AT samples, whereas Porphyromonas 1 increased. C) Grouping all BT samples (on the left of the graph) and all AT samples (on the right of the graph) confirmed the tendency observed per patient: after ivacaftor treatment, the RA of Streptococcus 1 decreased while that of Porphyromonas 1 increased.
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pone.0124124.g001: Relative abundance (RA) of OTUs belonging to the major core microbiota.A) RA of OTUs for the three patients (GM, PM, and RM) highlighted that each individual harbored his or her own microbiota, even if several genera were shared. B) RA of OTUs before ivacaftor treatment (BT) and after the beginning of ivacaftor treatment (AT) for each patient. RA of Streptococcus 1 showed a tendency to decrease from BT to AT samples, whereas Porphyromonas 1 increased. C) Grouping all BT samples (on the left of the graph) and all AT samples (on the right of the graph) confirmed the tendency observed per patient: after ivacaftor treatment, the RA of Streptococcus 1 decreased while that of Porphyromonas 1 increased.

Mentions: Each patient had a specific airway microbiota some OTUs being specific to one or two patients (results not shown). However, the 16 OTUs belonging to the core microbiota were shared by all patients, although the variability in their relative abundance clearly highlighted 8 OTUs (Fig 1A). They represented 7 genera (i.e., Veillonella, Streptococcus, Rothia, Prevotella, Porphyromonas, Gemella and Fusobacterium) belonging to the endogenous anaerobic microbiota of the oral airway, the composition of which is indistinguishable from the lung microbiota of healthy subjects [3]. Numerous studies have clearly demonstrated that their detection in sputum samples was not the consequence of oral contamination [23,24], which we confirmed by cytological scoring to evaluate salivary contamination. Furthermore, the presence of these bacterial genera suggested that the oral cavity may act as a reservoir for respiratory infection [25,26]. In all patients, Streptococcus 1, corresponding to the S. mitis group, was the most abundant OTU in the core microbiota, in agreement with Maeda’s findings that patients harbored at least 1 viridans streptococcus species, with strong prevalence for the S. mitis group [27].


Impact of the CFTR-potentiator ivacaftor on airway microbiota in cystic fibrosis patients carrying a G551D mutation.

Bernarde C, Keravec M, Mounier J, Gouriou S, Rault G, Férec C, Barbier G, Héry-Arnaud G - PLoS ONE (2015)

Relative abundance (RA) of OTUs belonging to the major core microbiota.A) RA of OTUs for the three patients (GM, PM, and RM) highlighted that each individual harbored his or her own microbiota, even if several genera were shared. B) RA of OTUs before ivacaftor treatment (BT) and after the beginning of ivacaftor treatment (AT) for each patient. RA of Streptococcus 1 showed a tendency to decrease from BT to AT samples, whereas Porphyromonas 1 increased. C) Grouping all BT samples (on the left of the graph) and all AT samples (on the right of the graph) confirmed the tendency observed per patient: after ivacaftor treatment, the RA of Streptococcus 1 decreased while that of Porphyromonas 1 increased.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390299&req=5

pone.0124124.g001: Relative abundance (RA) of OTUs belonging to the major core microbiota.A) RA of OTUs for the three patients (GM, PM, and RM) highlighted that each individual harbored his or her own microbiota, even if several genera were shared. B) RA of OTUs before ivacaftor treatment (BT) and after the beginning of ivacaftor treatment (AT) for each patient. RA of Streptococcus 1 showed a tendency to decrease from BT to AT samples, whereas Porphyromonas 1 increased. C) Grouping all BT samples (on the left of the graph) and all AT samples (on the right of the graph) confirmed the tendency observed per patient: after ivacaftor treatment, the RA of Streptococcus 1 decreased while that of Porphyromonas 1 increased.
Mentions: Each patient had a specific airway microbiota some OTUs being specific to one or two patients (results not shown). However, the 16 OTUs belonging to the core microbiota were shared by all patients, although the variability in their relative abundance clearly highlighted 8 OTUs (Fig 1A). They represented 7 genera (i.e., Veillonella, Streptococcus, Rothia, Prevotella, Porphyromonas, Gemella and Fusobacterium) belonging to the endogenous anaerobic microbiota of the oral airway, the composition of which is indistinguishable from the lung microbiota of healthy subjects [3]. Numerous studies have clearly demonstrated that their detection in sputum samples was not the consequence of oral contamination [23,24], which we confirmed by cytological scoring to evaluate salivary contamination. Furthermore, the presence of these bacterial genera suggested that the oral cavity may act as a reservoir for respiratory infection [25,26]. In all patients, Streptococcus 1, corresponding to the S. mitis group, was the most abundant OTU in the core microbiota, in agreement with Maeda’s findings that patients harbored at least 1 viridans streptococcus species, with strong prevalence for the S. mitis group [27].

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: EA 3882-Laboratoire Universitaire de Biodiversité et Ecologie Microbienne, Université de Brest, Brest, France.

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 and methods: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus