Microbes differ in lungs of CF and non-CF bronchiectasis: Study

Researchers say findings show need for tailored disease management

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by Steve Bryson, PhD |

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This illustration shows different types of bacteria in a cluster.

Despite some similarities, the lung composition of microbes and their antimicrobial resistance profiles differed between people with bronchiectasis and cystic fibrosis (CF) and those with non-CF bronchiectasis, a study found.

The findings suggest “the need for customized management strategies for each disease,” the researchers wrote in the study, “Comparative microbiome analysis in cystic fibrosis and non-cystic fibrosis bronchiectasis,” published in Respiratory Research.

Bronchiectasis occurs when the airways become irreversibly widened, mainly due to repeated infection that boosts inflammation and contributes to lung damage. This can occur due to CF, a genetic disease marked by the buildup of thick mucus in the lungs, which blocks the airways and makes it hard to breathe and clear infectious agents.

Bronchiectasis can also develop in the absence of CF, and this is known as non-CF bronchiectasis (NCFB). Both CF-related bronchiectasis and NCFB “are marked by recurrent infections, inflammatory exacerbations, and lung damage,” the researchers wrote.

Because infections are the primary drivers of bronchiectasis progression, the microbes within the lungs (lung microbiota) may shed light on changes to microbe composition and susceptibility to antimicrobial drugs in these patients.

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Analyzing DNA

The scientists collected nasal swabs and/or sputum (mucus coughed up from the lower airways) from 13 adults with CF-related bronchiectasis, 10 NCFB adult patients, and 12 healthy adults. DNA was extracted from samples and analyzed to identify different types of microbes.

Twelve CF patients and seven in the NCFB group were continuously treated with antimicrobial agents, and none of the CF patients had received CFTR modulator therapy. Most patients in both disease groups were chronically infected with Pseudomonas aeruginosa, a major contributor to lung disease in people with CF.

Both disease groups had lower microbiota richness in their sputum samples relative to healthy controls. However, this difference was not found in nasal samples, which represented the upper airways.

Both disease groups also showed significant differences in terms of microbiota community composition in sputum samples compared with the control group.

The findings were “likely influenced by antimicrobial therapy and the dominance of specific [microbes],” the researchers wrote.

The CF group had a significantly higher Bray-Curtis dissimilarity index, a measure of the dissimilarity between two samples. This underscored the wide variability of the microbiome composition in these individuals, the team noted. Samples from nasal swabs showed no significant differences across CF and NBCF patients, as well as controls.

“Sputum samples exhibited substantial dissimilarities in both the core composition of the microbiota and phylum-level comparisons,” the researchers wrote. Phylum refers to a major group of living organisms.

CF patients had only four types of core sputum microbes: Actinomyces — which were also found in healthy people — and Burkholderia, Cutibacterium, and Rhizobium, which were exclusive to this patient group.

The core composition in NCFB patients was made of Actinomyces and Campylobacter (also found in healthy people), Burkholderia, Cutibacterium, and Rhizobium (also found in CF patients), and Streptococcus, Capnocytophaga, Lautropia, and Treponema — with the last three being exclusive to the NCFB group.

The Firmicutes to Bacteroidetes (F/B) ratio, a widely accepted indicator of microbiota health, was significantly higher in sputum samples of the CF group than in those from the NCFB and healthy groups.

“This distinction in the F/B ratio was the sole dissimilarity observed between the CF and NCFB [patient groups],” the scientists wrote.

CF patients’ sputum samples were also more enriched with members of the Burkholderiaceae bacterial family and the Staphylococcus aureus strain than NBCF’s. In contrast, sputum samples from NCFB patients displayed more members of the Haemophilus influenzae and Prevotella shahii groups compared with CF patients.

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Fewer differences in nasal swabs

Fewer group differences were detected in nasal swabs.

A significantly higher frequency of genes related to antibiotic resistance was found in the sputum samples within the CF group compared with both NCFB and healthy groups. Nasal samples showed a significantly higher frequency of such genes in CF and NCFB patients relative to controls.

In both disease groups, enriched resistance genes in sputum samples were associated with antibiotic efflux, whereby bacteria pump antibiotics out from their cellular interior. Nearly all identified antibiotic-resistance genes in patients were found in Pseudomonas aeruginosa. These data correlated with clinical microbiological resistance as assessed in patients.

“Our study revealed distinct microbial compositions and resistance gene profiles in CF and NCFB patients compared to healthy subjects,” the scientists wrote. “While some similarities existed between the disease [groups], CF had a more pronounced impact on the lung [microbiota], evidenced by greater dissimilarity to the healthy [group].”

They added that nasal samples “exhibited a consistent microbiota composition across all cohorts, suggesting limited diagnostic value for this site.”

The findings “underscore the importance of tailored strategies for each disease, primarily antimicrobial agent selection in the context of antimicrobial resistance,” the team concluded.