Sputum microbiota in adults with CF associates with response to inhaled tobramycin.

Background: Inhaled tobramycin powder/solution (TIP/S) use has resulted in improved clinical outcomes in patients with cystic fibrosis (CF) with chronic . However, TIP/S effect on the CF sputum microbiome has not been explored. We hypothesised that TIP/S has additional 'off-target' effects beyond merely and that baseline microbiome prior to initiation of therapy is associated with subsequent patient response.

Methods: We drew sputum samples from a prospectively collected biobank. Patients were included if they had one sputum sample in the 18 months before and after TIP/S. Bacterial 16S rRNA gene profiling was used to characterise the sputum microbiome.

Results: Forty-one patients met our inclusion criteria and 151 sputum samples were assessed. At baseline, median age was 30.4 years (IQR 24.2-35.2) and forced expiratory volume in 1 (FEV) second was 57% predicted (IQR 44-74). Nineteen patients were defined a priori as responders having no net decrease in FEV in the year following TIP/S. No significant changes were observed in key microbiome metrics of alpha (within-sample) or beta (between-sample) diversity for samples collected before and after TIP/S. However, significant beta-diversity (Bray-Curtis) differences were noted at baseline between patients based on response status. Notably, responders were observed to have a higher abundance of in pretherapy baseline samples.

Conclusions: Our longitudinal study demonstrates that the sputum microbiome of patients with CF is relatively stable following inhaled tobramycin over many months. Intriguingly, our findings suggest that baseline microbiome may associate with patient response to TIP/S-suggesting the sputum microbiome could be used to personalise therapy.