Microbial community organization of pulmonary exacerbation types in cystic fibrosis

Persons with cystic fibrosis (CF) harbor a polymicrobial lung microbiome that contributes to intermittent episodes of acute respiratory symptoms (PEx) causing lung function decline and mortality. Due to high subject-specificity of lung microbiota, underlying PEx communalities remained elusive. Here, we developed non-standard descriptors for 16S sequenced microbiomes, and modeled community reorganization before and during PEx. We identified two communal dysbiosis regimes with opposing ecological dynamics and organization. Pathogen dysbiosis showed reduced diversity and turnover, marked network hierarchy, and pathogen governance. Anaerobic bloom dysbiosis displayed increased diversity, turnover, and stochasticity. Importantly, microbiome organization modulated the relevance of conventional CF pathogens for community dynamics and a model of simulated pathogen removal from data-derived co-occurrence networks predicted augmented treatment efficacy for hierarchically organized microbiota. This study reveals a causal link between PEx, microbiome organization and treatment success and thereby advances the development of personalized microbiome management.