Microbial community organization designates distinct pulmonary exacerbation types and predicts treatment outcome in cystic fibrosis

Abstract

Polymicrobial infection of the airways is a hallmark of obstructive lung diseases such as cystic fibrosis (CF), non-CF bronchiectasis, and chronic obstructive pulmonary disease (COPD). Intermittent pulmonary exacerbations (PEx) in these conditions are associated with lung function decline and higher mortality rates. An understanding of the microbial underpinnings of PEx is challenged by high inter-patient variability in airway microbial community profiles. We analyzed 880 near-daily CF sputum samples and developed non-standard microbiome descriptors to model community reorganization prior and during 18 PEx. We identified two communal microbial regimes with opposing ecology and dynamics. Whereas pathogen-governed dysbiosis showed hierarchical community organization and reduced diversity, anaerobic bloom dysbiosis displayed stochasticity and increased diversity. Microbiome organization modulated the relevance of pathogens and a simulation of antimicrobial treatment predicted better efficacy for hierarchically organized microbiota. This causal link between PEx, microbiome organization, and treatment success advances the development of personalized dysbiosis management in CF and, potentially, other obstructive lung diseases.