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

Abstract

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.IMPORTANCEThe influence of NTM infection in pwCF is still debated, and the extent of their contribution to mortality and morbidity is still questioned. Findings in this study highlight a link between the presence of NTMs and significant alterations in the composition of the respiratory microbiome, particularly with respect to some of the canonical CF pathogens, especially Pseudomonas aeruginosa and members of the Burkholderia cepacia complex. This indicates that complex relationships are occurring within the microbiome. This study further contributes to the understanding of NTM infection in pwCF, with and without CFTR modulator therapy, and highlights the need for further research in this area. The knowledge gained from this study has implications for treatment strategies and management, ultimately aiming to improve and prolong the lives of pwCF.

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