Patients with CF-related diabetes show imbalanced lung bacteria
Study also links CFRD to airway inflammation, lower lung function
Written by |
People with cystic fibrosis-related diabetes (CFRD) show alterations in the lung microbiome, the community of microbes that live in the lungs, a study from Sweden found.
These alterations are characterized by reduced diversity of bacterial types and more imbalanced bacterial composition. The study also demonstrated that patients with CFRD had lower lung function and elevated airway inflammation.
The “decreased microbial diversity observed in [people with] CFRD was predominantly driven by impaired lung function rather than by CFRD itself,” the researchers wrote.
The study, “Cystic fibrosis-related diabetes is associated with reduced airway microbial diversity,” was published in Respiratory Research.
CF is caused by genetic mutations that result in the loss or dysfunction of the CFTR protein, leading to the accumulation of thick, sticky mucus in various organs, particularly the lungs. The abnormal buildup of mucus in the lungs creates a fertile breeding ground for bacteria, which can lead to frequent lung infections and structural damage that reduces lung function.
Lung microbiome
Outside the lungs, CFRD, a condition marked by elevated blood sugar (glucose), is the most common complication of cystic fibrosis. In a previously published study, researchers linked CFRD to reduced lung function and increased levels of pro-inflammatory molecules in the lungs.
Building on these findings, the team examined associations between the lung microbiome and CFRD. They recruited 44 adults with CF at Skåne University Hospital Lund, 26 of whom (59.1%) had CFRD. Participants had a median age of 36, and 73% were men. Eleven percent of the participants used Kaftrio (elexacaftor, tezacaftor, and ivacaftor), sold as Trikafta in the U.S.
Those with CFRD had significantly worse lung function, as assessed by FEV1pp (61.9% vs. 86.2%), which measures the amount of air a person can forcefully exhale in one second, compared with norms with similar age, sex, height, and ethnicity. They also had elevated HbA1c (44.5mmol/mol vs. 37 mmol/mol), a test that measures the average sugar levels in the previous two to three months.
CFRD patients had elevated levels of pro-inflammatory interleukin (IL)-1 beta and lower levels of IL-6, which has both pro- and anti-inflammatory activity, depending on the signaling pathway.
Genetic testing identified the types and abundance of bacteria in lung sputum samples. The team calculated both alpha diversity (the microbial diversity within a sample) and beta diversity, which reflects microbial differences between samples.
While the total number of bacterial types did not differ between CFRD and non-CFRD, the Shannon index, which accounts for the total number of species and for their relative abundance, was significantly lower in the CFRD group. This indicates that CF patients with diabetes have lower bacterial diversity and a more uneven microbial community in the lungs, the team noted.
A statistical analysis indicated that CFRD was associated with lower bacterial diversity measured by the Shannon index, but the link was no longer seen after adjusting for patients’ lung function. Instead, lung function was indeed associated with bacterial diversity.
“These results indicate that the reduced Shannon diversity observed in [people with] CFRD is predominantly driven by impaired lung function, an integral component of the clinical [features] of CFRD, rather than by CFRD itself,” the researchers wrote.
Beta diversity analysis did not reveal a significant difference between the CFRD and non-CFRD groups, “suggesting that CFRD status alone does not drive major shifts in overall bacterial community composition,” the researchers wrote. But further analysis showed that lung function and IL-1 beta levels were significantly associated with microbial composition.
Regarding bacterial genera, Pseudomonas and Staphylococcus, which are known drivers of lung infections in people with CF, were common in both groups. Conversely, Abiotrophia, Anaeroglobus, and Escherichia-Shigella were significantly more frequent in the CFRD group, while Neisseria, Prevotella, and Streptococcus were more abundant in those without CFRD.
“While CFRD status alone did not significantly alter overall microbial community composition, the enrichment of Escherichia/Shigella in individuals with CFRD, alongside a relative depletion of genera linked to healthier airway profiles, further suggests a shift towards a dysbiotic [imbalanced] microbial composition,” the team concluded.
