Abstract

Cystic fibrosis-related diabetes (CFRD) affects 40%-50% of adults with CF and is associated with a decline in respiratory health. The microbial flora of the lung is known to change with the development of CF disease, but how CFRD affects the microbiome has not been described. We analyzed the microbiome in sputa from 14 people with CF, 14 with CFRD, and two who were classed as pre-CFRD by extracting DNA and amplifying the variable V3-V4 region of the microbial 16S ribosomal RNA gene by PCR. Sequences were analyzed and sources were identified to genus level. We found that the α-diversity of the microbiome using Shannon's diversity index was increased in CFRD compared with CF. Bray Curtis dissimilarity analysis showed that there was separation of the microbiomes in CF and CFRD sputa. The most abundant phyla identified in the sputum samples were Firmicutes and Proteobacteria, Actinobacteriota and Bacteroidota, and the ratio of Firmicutes/Bacteroidota was reduced in CFRD compared with CF. Pseudomonas, Azhorizophilus, Porphyromonas, and Actinobacillus were more abundant in CFRD compared with CF, whereas Staphylococcus was less abundant. The relative abundance of these genera did not correlate with age; some correlated with a decline in FEV1/FVC but all correlated with hemoglobin A1C (HbA1c) indicating that development of CFRD mediates further changes to the respiratory microbiome in CF.NEW & NOTEWORTHY Cystic fibrosis-related diabetes (CFRD) is associated with a decline in respiratory health. We show for the first time that there was a change in the sputum microbiome of people with CFRD compared with CF that correlated with markers of raised blood glucose.