Frontiers in Microbiology (May 2022)
Changes in Microbiome Dominance Are Associated With Declining Lung Function and Fluctuating Inflammation in People With Cystic Fibrosis
- Dario L. Frey,
- Dario L. Frey,
- Calum Bridson,
- Calum Bridson,
- Susanne Dittrich,
- Susanne Dittrich,
- Susanne Dittrich,
- Simon Y. Graeber,
- Simon Y. Graeber,
- Simon Y. Graeber,
- Simon Y. Graeber,
- Simon Y. Graeber,
- Simon Y. Graeber,
- Mirjam Stahl,
- Mirjam Stahl,
- Mirjam Stahl,
- Mirjam Stahl,
- Mirjam Stahl,
- Mirjam Stahl,
- Sabine Wege,
- Felix Herth,
- Felix Herth,
- Olaf Sommerburg,
- Olaf Sommerburg,
- Carsten Schultz,
- Carsten Schultz,
- Alexander Dalpke,
- Alexander Dalpke,
- Alexander Dalpke,
- Marcus A. Mall,
- Marcus A. Mall,
- Marcus A. Mall,
- Sébastien Boutin,
- Sébastien Boutin
Affiliations
- Dario L. Frey
- Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany
- Dario L. Frey
- Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany
- Calum Bridson
- Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany
- Calum Bridson
- Department of Infectious Diseases, Medical Microbiology and Hygiene, University of Heidelberg, Heidelberg, Germany
- Susanne Dittrich
- Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany
- Susanne Dittrich
- Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany
- Susanne Dittrich
- Department of Pneumology and Critical Care Medicine, Thoraxklinik at the University Hospital Heidelberg, Heidelberg, Germany
- Simon Y. Graeber
- Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany
- Simon Y. Graeber
- Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany
- Simon Y. Graeber
- Division of Pediatric Pulmonology and Allergology and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany
- Simon Y. Graeber
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Simon Y. Graeber
- Berlin Institute of Health (BIH), Berlin, Germany
- Simon Y. Graeber
- German Center for Lung Research (DZL), Associated Partner Site, Berlin, Germany
- Mirjam Stahl
- Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany
- Mirjam Stahl
- Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany
- Mirjam Stahl
- Division of Pediatric Pulmonology and Allergology and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany
- Mirjam Stahl
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Mirjam Stahl
- Berlin Institute of Health (BIH), Berlin, Germany
- Mirjam Stahl
- German Center for Lung Research (DZL), Associated Partner Site, Berlin, Germany
- Sabine Wege
- Department of Pneumology and Critical Care Medicine, Thoraxklinik at the University Hospital Heidelberg, Heidelberg, Germany
- Felix Herth
- Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany
- Felix Herth
- Department of Pneumology and Critical Care Medicine, Thoraxklinik at the University Hospital Heidelberg, Heidelberg, Germany
- Olaf Sommerburg
- Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany
- Olaf Sommerburg
- Division of Pediatric Pulmonology and Allergology and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany
- Carsten Schultz
- Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany
- Carsten Schultz
- Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR, United States
- Alexander Dalpke
- Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany
- Alexander Dalpke
- Department of Infectious Diseases, Medical Microbiology and Hygiene, University of Heidelberg, Heidelberg, Germany
- Alexander Dalpke
- 0Institute of Medical Microbiology and Virology, Technische Universität Dresden, Dresden, Germany
- Marcus A. Mall
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Marcus A. Mall
- Berlin Institute of Health (BIH), Berlin, Germany
- Marcus A. Mall
- German Center for Lung Research (DZL), Associated Partner Site, Berlin, Germany
- Sébastien Boutin
- Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany
- Sébastien Boutin
- Department of Infectious Diseases, Medical Microbiology and Hygiene, University of Heidelberg, Heidelberg, Germany
- DOI
- https://doi.org/10.3389/fmicb.2022.885822
- Journal volume & issue
-
Vol. 13
Abstract
Airway inflammation and microbiome dysbiosis are hallmarks of cystic fibrosis (CF) lung disease. However, longitudinal studies are needed to decipher which factors contribute to the long-term evolution of these key features of CF. We therefore evaluated the relationship between fluctuation in microbiome and inflammatory parameters in a longitudinal study including a short- (1-year) and a long-term (3+ years) period. We collected 118 sputum samples from 26 CF adult patients and analyzed them by 16S rRNA gene sequencing. We measured the levels of inflammatory cytokines, neutrophil elastase, and anti-proteinases; lung function (FEV1% predicted); and BMI. The longitudinal evolution was analyzed based on (i) the rates of changes; (ii) the intra-patient stability of the variables; and (iii) the dependency of the rates of changes on the baseline values. We observed that the diversity of the microbiome was highly variable over a 1-year period, while the inflammatory markers showed a slower evolution, with significant changes only observed in the 3+ year cohort. Further, the degree of fluctuation of the biomass and the dominance of the microbiome were associated with changes in inflammatory markers, especially IL-1β and IL-8. This longitudinal study demonstrates for the first time that the long-term establishment and periodical variation of the abundance of a dominant pathogen is associated with a more severe increase in inflammation. This result indicates that a single time point or 1-year study might fail to reveal the correlation between microbial evolution and clinical degradation in cystic fibrosis.
Keywords
