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

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. Pulmonary exacerbations (PEx) in these conditions are associated with accelerated 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 bacterial communities in 880 CF sputum samples and developed microbiome descriptors to model community reorganization prior to and during 18 PEx. We identified two microbial dysbiosis regimes with opposing ecology and dynamics. Pathogen-governed PEx showed hierarchical community reorganization and reduced diversity, whereas anaerobic bloom PEx displayed stochasticity and increased diversity. A simulation of antimicrobial treatment predicted better efficacy for hierarchically organized communities. This link between PEx type, microbiome organization, and treatment success advances the development of personalized clinical management in CF and, potentially, other obstructive lung diseases.