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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

Analysis of microbiota data for the 20 CF sputum samples based on non-phylogenetic distances.A) Principal coordinate analysis of microbial community structure per patient using Bray Curtis distances. PC1 and PC2 represented 55.3% of the variability. Red triangles: patient GM’s samples. Green circles: patient PM’s samples. Blue squares: patient RM’s samples. B) UPGMA clustering of samples using Bray Curtis distances. BT samples are represented by red branches and AT samples by blue branches. The scale bar represents a 5% sequence divergence.
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pone.0124124.g002: Analysis of microbiota data for the 20 CF sputum samples based on non-phylogenetic distances.A) Principal coordinate analysis of microbial community structure per patient using Bray Curtis distances. PC1 and PC2 represented 55.3% of the variability. Red triangles: patient GM’s samples. Green circles: patient PM’s samples. Blue squares: patient RM’s samples. B) UPGMA clustering of samples using Bray Curtis distances. BT samples are represented by red branches and AT samples by blue branches. The scale bar represents a 5% sequence divergence.

Mentions: To go further in the comparison of the community structure of samples, principal coordinate analysis (PCoA) and unweighted pair-group method using average linkages (UPGMA) clustering were performed using Bray-Curtis (Fig 2) and UniFrac (S2 Fig) distance metrics. Both analyses highlighted a clustering of samples from patient GM (Pseudomonas aeruginosa (Pa) status: “never”), whereas the Pa-intermittent patients RM and PM exhibited more similar microbiotas (Figs 2 and S2; see Table 1 for patient characteristics). This may suggest that, whereas it was thought that each CF patient harbors a specific airway microbiota [8], shared microbiological history, such as P. aeruginosa acquisition, can make for common points in the microbiota. Moreover, patient GM was the only one who was not under antibiotherapy at the time of sampling (Table 1), which could also be an explanation. Likewise, principal component analysis (PCA) distinguished GM’s samples, which were all negatively located on the F1 axis (Fig 3).


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)

Analysis of microbiota data for the 20 CF sputum samples based on non-phylogenetic distances.A) Principal coordinate analysis of microbial community structure per patient using Bray Curtis distances. PC1 and PC2 represented 55.3% of the variability. Red triangles: patient GM’s samples. Green circles: patient PM’s samples. Blue squares: patient RM’s samples. B) UPGMA clustering of samples using Bray Curtis distances. BT samples are represented by red branches and AT samples by blue branches. The scale bar represents a 5% sequence divergence.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0124124.g002: Analysis of microbiota data for the 20 CF sputum samples based on non-phylogenetic distances.A) Principal coordinate analysis of microbial community structure per patient using Bray Curtis distances. PC1 and PC2 represented 55.3% of the variability. Red triangles: patient GM’s samples. Green circles: patient PM’s samples. Blue squares: patient RM’s samples. B) UPGMA clustering of samples using Bray Curtis distances. BT samples are represented by red branches and AT samples by blue branches. The scale bar represents a 5% sequence divergence.
Mentions: To go further in the comparison of the community structure of samples, principal coordinate analysis (PCoA) and unweighted pair-group method using average linkages (UPGMA) clustering were performed using Bray-Curtis (Fig 2) and UniFrac (S2 Fig) distance metrics. Both analyses highlighted a clustering of samples from patient GM (Pseudomonas aeruginosa (Pa) status: “never”), whereas the Pa-intermittent patients RM and PM exhibited more similar microbiotas (Figs 2 and S2; see Table 1 for patient characteristics). This may suggest that, whereas it was thought that each CF patient harbors a specific airway microbiota [8], shared microbiological history, such as P. aeruginosa acquisition, can make for common points in the microbiota. Moreover, patient GM was the only one who was not under antibiotherapy at the time of sampling (Table 1), which could also be an explanation. Likewise, principal component analysis (PCA) distinguished GM’s samples, which were all negatively located on the F1 axis (Fig 3).

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