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

• Published in: Nature communications Vol. 15; no. 1; pp. 4889 - 13
• Main Authors: Widder, Stefanie, Carmody, Lisa A., Opron, Kristopher, Kalikin, Linda M., Caverly, Lindsay J., LiPuma, John J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.06.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 45; 45/23; 631/114/2397; 631/250/254; 631/326/2565/2134; Adolescent; Adult; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Bacteria - classification; Bacteria - genetics; Bacteria - isolation & purification; Bronchiectasis; Chronic obstructive pulmonary disease; Community structure; Cystic fibrosis; Cystic Fibrosis - microbiology; Disease Progression; Dysbacteriosis; Dysbiosis - microbiology; Female; Health services; Humanities and Social Sciences; Humans; Lung - microbiology; Lung diseases; Male; Microbiomes; Microbiota; Microorganisms; multidisciplinary; Pathogens; Prospective Studies; Pulmonary Disease, Chronic Obstructive - microbiology; Respiratory function; Respiratory tract; Science; Science (multidisciplinary); Signs and symptoms; Sputum; Sputum - microbiology; Stochasticity; Treatment Outcome; Young Adult
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-49150-y

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. Understanding PEx ecology is challenged by high inter-patient variability in airway microbial community profiles. We analyze bacterial communities in 880 CF sputum samples collected during an observational prospective cohort study and develop microbiome descriptors to model community reorganization prior to and during 18 PEx. We identify two microbial dysbiosis regimes with opposing ecology and dynamics. Pathogen-governed PEx show hierarchical community reorganization and reduced diversity, whereas anaerobic bloom PEx display stochasticity and increased diversity. A simulation of antimicrobial treatment predicts better efficacy for hierarchically organized communities. This link between PEx, microbiome organization, and treatment success advances the development of personalized clinical management in CF and, potentially, other obstructive lung diseases. In this work, authors show that exacerbations of respiratory symptoms in persons with cystic fibrosis (CF) were associated with either CF pathogen-driven or anaerobe-based changes in airway bacterial community structure.