Changes in Microbiome Dominance Are Associated With Declining Lung Function and Fluctuating Inflammation in People With Cystic Fibrosis

Dario L Frey, Calum Bridson, Susanne Dittrich, Simon Y Graeber, Mirjam Stahl, Sabine Wege, Felix Herth, Olaf Sommerburg, Carsten Schultz, Alexander Dalpke, Marcus A Mall, Sébastien Boutin

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.

Original languageEnglish
JournalFrontiers in Microbiology
Volume13
Pages (from-to)885822
ISSN1664-302X
DOIs
Publication statusPublished - 2022

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

DFG Research Classification Scheme

  • 204-03 Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology

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