Abstract
Bacterial infection and inflammation of the airways are the leading causes of morbidity and mortality in persons with cystic fibrosis (CF). The ecology of the bacterial communities inhabiting CF airways is poorly understood, especially with respect to how community structure, dynamics, and microbial metabolic activity relate to clinical outcomes. In this study, the bacterial communities in 818 sputum samples from 109 persons with CF were analyzed by sequencing bacterial 16S rRNA gene amplicons. We identified eight alternative community types (pulmotypes) by using a Dirichlet multinomial mixture model and studied their temporal dynamics in the cohort. Across patients, the pulmotypes displayed chronological patterns in the transition among each other. Furthermore, significant correlations between pulmotypes and patient clinical status were detected by using multinomial mixed effects models, principal components regression, and statistical testing. Constructing pulmotype-specific metabolic activity profiles, we found that pulmotype microbiota drive distinct community functions including mucus degradation or increased acid production. These results indicate that pulmotypes are the result of ordered, underlying drivers such as predominant metabolism, ecological competition, and niche construction and can form the basis for quantitative, predictive models supporting clinical treatment decisions.
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Data availability
The sequencing data are available in the NCBI Bioproject database (accession numbers: PRJNA423040, PRJNA756039). Detailed SRA accession numbers are additionally listed as Supplementary information.
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Acknowledgements
We gratefully acknowledge the many individuals who provided the sputum samples used in this study. We thank the Michigan Medicine clinical microbiology laboratory for the generous assistance in obtaining sputum samples for this study. We thank Prof. Barbara Bailey for fruitful discussions about random forests. This study was funded by NHLBI grants 1RC1HL100809 and 1R01HL136647 to JJL. Additional support was provided by NIH CTSA grant UL1RR024986 and the Charles Woodson Pediatric Research Fund. SW was supported by the Austrian Science Fund (FWF) Elise Richter V585-B31.
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SW provided conceptualization, investigation, methodology, formal analysis, visualization, writing—original draft, and writing—review and editing. JZ conducted methodology, formal analysis, visualization, writing—original draft, and writing—review and editing. LAC contributed investigation, data curation, writing—original draft, and writing—review and editing. QZ and PDS provided software and supported data curation. LMK contributed to data curation, project administration, and writing—review and editing. JJL contributed to conceptualization, funding acquisition, resources, supervision, writing—original draft, and writing—review and editing.
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Widder, S., Zhao, J., Carmody, L.A. et al. Association of bacterial community types, functional microbial processes and lung disease in cystic fibrosis airways. ISME J 16, 905–914 (2022). https://doi.org/10.1038/s41396-021-01129-z
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DOI: https://doi.org/10.1038/s41396-021-01129-z
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