Cystic fibrosis-related diabetes is associated with reduced airway microbial diversity

BACKGROUND: Cystic fibrosis (CF) is a genetic disorder characterized by chronic airway inflammation and lung function decline. CF-related diabetes (CFRD) is the main extrapulmonary complication and it is tightly linked to an impaired lung function, but the underlying mechanisms behind these observations are incompletely understood. In the present study, we aimed to compare airway microbiome compositions between pwCF with and without CFRD. METHODS: Sputum samples from pwCF with and without CFRD were analysed for inflammatory cytokines using MesoScale assays and total bacterial load using quantitative PCR of the 16s rRNA gene. Bacterial sputum microbiomes were analysed with 16s rRNA sequencing and characterized based on richness and evenness. Bray-Curtis was used to determine the distance in microbiome compositions between samples. RESULTS: Forty-four pwCF were included, of which 59% were diagnosed with CFRD. The CFRD group had significantly lower lung function and elevated sputum levels of IL-1β compared to pwCF without CFRD. The CFRD sputum microbiome was characterized by reduced bacterial diversity, but this association was attenuated after adjusting for lung function. The distance in microbiome composition did not differ between groups. Abiotrophia, Anaeroglobus and Escherichia-Shigella were significantly enriched in the CFRD group, while Neisseria, Prevotella and Streptococcus were more abundant in pwCF without CFRD. CONCLUSION: CFRD is associated with impaired lung function, elevated airway inflammation, and a sputum microbiome characterized by reduced bacterial diversity and a more dysbiotic composition. The decreased microbial diversity observed in pwCF with CFRD was predominantly driven by impaired lung function rather than by CFRD itself.