INTRODUCTION AND AIM Ivacaftor (Kalydeco), a CFTR potentiator for cystic fibrosis (CF) patients with the G551D mutation, improves lung function and reduces pulmonary exacerbations. However, the impact of Ivacaftor on airway microbial community composition and structure is poorly defined. The aim of this study was to determine if Ivacaftor treatment is associated with changes in the lower airway microbiota. METHODS Sputum samples (n=64) were collected from adult CF patients (n=21) at a single centre; samples were collected at initiation of Ivacaftor treatment +/- after 3, 6, 9 and 12 months of treatment. FEV1 (% predicted) was recorded at each timepoint. Molecular based analysis (Illumina MiSeq) was performed to assess differences in the lower airway microbiota. This included differences in taxonomic richness, community diversity (Shannon-Wiener Index), relative abundance and co-occurrence. We considered a valid correlation between specific taxa and changes in lung function, community richness and diversity based on the Spearman’s correlation coefficient (ρ) of >0.5 and adjusted P<0.05 (Bonferroni correction). Co-occurrence between two different taxa was considered valid if the Spearman’s correlation coefficient (ρ) was both >0.5 and adjusted P<0.005 (Benjamini-Hochberg-Yekutieli correction). RESULTS There was no significant differences in the overall community richness and diversity between time points [P>0.05]. However, significant intra-individual differences were observed for the majority of samples over the course of the study. The mean % predicted FEV1 increase between pre-treatment and the last available post-treatment visit was 12% (range -9% to 58%). For 14 patients, we observed changes in % predicted FEV1 that paralleled changes in both taxonomic richness and diversity. In a number of cases, a reduction in Pseudomonas spp. and an increase in Streptococcus spp. and a number of anaerobic taxa was apparent. The observed community richness and diversity negatively correlated with a higher proportion of Pseudomonas spp. [ρ=-0.65; P<0.005]. Conversely, increased taxonomic richness and diversity positively correlated with a higher proportion of Streptococcus spp. [ρ>0.5; P<0.005] and anaerobic taxa such as Prevotella spp., Veillonella spp., Fusobacterium spp. and Actinomyces spp. [ρ>0.5; P<0.005]. Co-occurrence network analysis showed a significant correlation between Streptococcus spp., Prevotella spp. and Veillonella spp. [ρ>0.5; P<0.005]. Potential pathogenic taxa, such as Pseudomonas spp., Staphylococcus spp. and Stenotrophomonas spp. did not co-occur with any other taxa in their respective communities. DISCUSSION Ivacaftor treatment resulted in a significant improvement in lung function. Concurrent changes in lung function and microbiota were observed in a significant number of cases. Further analysis is required to better define the effect of Ivacaftor on airway microbial community composition and structure. FUNDING Supported through CFMATTERS, a Seventh Framework Programme Project No. 603038.
|Publication status||Published - 2016|