Abstract
RATIONALE: Pulmonary infections with nontuberculous mycobacteria (NTM) are increasingly prevalent in people with cystic fibrosis (CF). Clinical outcomes following NTM acquisition are highly variable, ranging from transient self-resolving infection to NTM pulmonary disease associated with significant morbidity. Relationships between airway microbiota and variability of NTM outcomes in CF are unclear. OBJECTIVE: To identify features of CF airway microbiota associated with outcomes of NTM infection. METHODS: 188 sputum samples, obtained from 24 subjects with CF, each with three or more samples collected from 3.5 years prior to, and up to 6 months following incident NTM infection, were selected from a sample repository. Sputum DNA underwent bacterial 16S rRNA gene sequencing. Airway microbiota were compared based on the primary outcome, a diagnosis of NTM pulmonary disease, using Wilcoxon rank-sum testing, autoregressive integrated moving average modelling and network analyses. MEASUREMENTS AND MAIN RESULTS: Subjects with and without NTM pulmonary disease were similar in clinical characteristics, including age and lung function at the time of incident NTM infection. Time-series analyses of sputum samples prior to incident NTM infection identified positive correlations between Pseudomonas, Streptococcus, Veillonella, Prevotella and Rothia with diagnosis of NTM pulmonary disease and with persistent NTM infection. Network analyses identified differences in clustering of taxa between subjects with and without NTM pulmonary disease, and between subjects with persistent versus transient NTM infection. CONCLUSIONS: CF airway microbiota prior to incident NTM infection are associated with subsequent outcomes, including diagnosis of NTM pulmonary disease, and persistence of NTM infection. Associations between airway microbiota and NTM outcomes represent targets for validation as predictive markers and for future therapies.