Nontuberculous mycobacteria remodel lung microbiota in cystic fibrosis-associated respiratory infections

Nontuberculous mycobacterial (NTM) infections in people with cystic fibrosis (pwCF) can have detrimental effects on prognosis and pose significant challenges to treatment. However, there are still questions regarding the contribution and influence of NTMs on the respiratory microbiome and the mechanisms by which NTMs cause infections. Here, we investigate the impact of NTM infection on microbiome composition and lung function (percent predicted forced expiratory volume in 1 second). Primary comparisons were between culture-positive cohorts for Mycobacterium avium complex and Mycobacterium abscessus complex and those who were culture-negative for NTMs and attending outpatient clinics. Additionally, the consequence of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy status and positive NTM culture was assessed in terms of microbiome change. Our data suggest that the presence of NTM significantly alters the diversity and the composition of the lung microbiota in pwCF, including those receiving CFTR modulator therapies. Importantly, significant associations were detected between NTM presence and changes in abundance of Pseudomonas aeruginosa and Burkholderia cepacia complex members, inferring modulatory effects of NTMs on respiratory microbiomes. This study contributes to the understanding of NTM infection and these organisms’ interaction with the respiratory microbiome and CFTR modulator therapy, highlighting the need for further research in this area.