Relationship between airway dysbiosis, inflammation and lung function in adults with cystic fibrosis

Dario L Frey; Sébastien Boutin; Susanne A Dittrich; Simon Y Graeber; Mirjam Stahl; Sabine Wege; Felix J F Herth; Olaf Sommerburg; Carsten Schultz; Marcus A Mall; Alexander H Dalpke

doi:10.1016/j.jcf.2020.12.022

Relationship between airway dysbiosis, inflammation and lung function in adults with cystic fibrosis

J Cyst Fibros. 2021 Sep;20(5):754-760. doi: 10.1016/j.jcf.2020.12.022. Epub 2021 Jan 8.

Authors

Affiliations

¹ Translational Lung Research Center (TLRC), Heidelberg, Germany; Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany.
² Translational Lung Research Center (TLRC), Heidelberg, Germany; Department of Infectious Diseases, Medical Microbiology and Hygiene, University of Heidelberg, Heidelberg, Germany. Electronic address: sebastien.boutin@med.uni-heidelberg.de.
³ Translational Lung Research Center (TLRC), Heidelberg, Germany; Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany; Department of Pneumology and Critical Care Medicine, Thoraxklinik at the University Hospital Heidelberg, Heidelberg, Germany.
⁴ Translational Lung Research Center (TLRC), Heidelberg, Germany; Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany; Division of Pediatric Pulmonology & Allergology and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany; Department of Pediatric Pulmonology, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charité-Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany; German Center for Lung Research (DZL), associated partner site, Berlin, Germany.
⁵ Translational Lung Research Center (TLRC), Heidelberg, Germany; Department of Translational Pulmonology, University of Heidelberg, Heidelberg, Germany; Division of Pediatric Pulmonology & Allergology and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany; Department of Pediatric Pulmonology, Immunology and Critical Care Medicine and Cystic Fibrosis Center, Charité-Universitätsmedizin Berlin, Berlin, Germany; German Center for Lung Research (DZL), associated partner site, Berlin, Germany.
⁶ Department of Pneumology and Critical Care Medicine, Thoraxklinik at the University Hospital Heidelberg, Heidelberg, Germany.
⁷ Translational Lung Research Center (TLRC), Heidelberg, Germany; Department of Pneumology and Critical Care Medicine, Thoraxklinik at the University Hospital Heidelberg, Heidelberg, Germany.
⁸ Translational Lung Research Center (TLRC), Heidelberg, Germany; Division of Pediatric Pulmonology & Allergology and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany.
⁹ Translational Lung Research Center (TLRC), Heidelberg, Germany; Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, OR, USA.
¹⁰ Translational Lung Research Center (TLRC), Heidelberg, Germany; Department of Infectious Diseases, Medical Microbiology and Hygiene, University of Heidelberg, Heidelberg, Germany; Institute of Medical Microbiology and Hygiene, Technische Universität Dresden, Dresden, Germany.

PMID: 33431308
DOI: 10.1016/j.jcf.2020.12.022

Abstract

Airway dysbiosis has been associated with lung disease severity in patients with cystic fibrosis (CF). However, the relationship between dysbiosis, airway inflammation and lung function impairement remains poorly understood. The aim of this study was therefore to determine how the structure of the sputum microbiota, airway inflammation markers and spirometry are related in patients with CF. Sputum samples were collected from 106 CF patients between 12 and 72 years. These were analyzed by 16S rRNA gene amplicon sequencing. Moreover, levels of pro-inflammatory cytokines (IL-1β, IL-8, IL-6 and TNF-α) and Neutrophil elastase (NE) were determined. The relationship between the microbiota, inflammation markers and forced expiratory volume in one second percent predicted (FEV₁% predicted) was evaluated by multi-parameter analysis. The microbiota α-diversity correlated inverse with inflammation markers IL-1β, IL-8, TNF-α, NE and positively with FEV₁% predicted. Patients could be divided into 7 clusters based on their microbiota structure. The most diverse cluster was defined by oropharyngeal-like flora (OF) while the others were characterized by the dominance of a single pathogen. Patients with the diverse OF microbiota cluster had lower sputum inflammatory markers and higher FEV₁% predicted compared to patients with a pathogen-dominated microbiota including Pseudomonas aeruginosa. Our results suggest that the diversity of the airway microbiota is an important biomarker of the severity of airway inflammation linking dysbiosis to lung function decline in patients with CF.

Keywords: Cystic fibrosis; Inflammation; Lung function; Microbiome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Biomarkers
Child
Cross-Sectional Studies
Cystic Fibrosis / microbiology*
Cystic Fibrosis / physiopathology*
Dysbiosis / microbiology*
Dysbiosis / physiopathology*
Female
Humans
Inflammation / microbiology*
Inflammation / physiopathology*
Male
Middle Aged
Respiratory Function Tests
Sputum / microbiology
Young Adult

Substances

Biomarkers