Reduced sputum microbiome diversity is associated with greater disease severity in bronchiectasis, according to a new prospective study. It was also associated with a higher frequency and severity of exacerbations, as well as the risk of death.
“Given the central role of infection in the pathogenesis of bronchiectasis, the microbiome represents a potential area for improved disease understanding and stratification,” wrote study authors led by Dr Alison Dicker, of the University of Dundee, UK, in The Lancet Respiratory Medicine.
Previous small studies have described the bronchiectasis lung microbiome, but included only specific subsets of patients, and whether microbiome diversity or composition correlate with clinical phenotypes was previously unknown.
In total, the researchers obtained sequencing data from the sputum samples of 281 patients with bronchiectasis; 49 of those patients (17%) provided more than one sample when clinically stable, and were included in a longitudinal analysis.
Sputum from stable bronchiectasis as well as exacerbations was dominated by Proteobacteria and Firmicutes; individual patients’ microbiomes were relatively stable over time, including during exacerbations.
Lower diversity of the microbiome was associated with more severe bronchiectasis, lower FEV1, and more severe symptoms. Specifically, Pseudomonas, Enterobacteriaceae, and Stenotrophomonas were associated with more severe bronchiectasis as well as greater lung inflammation. Pseudomonas and Enterobacteriaceae were associated with more frequent exacerbations.
Patients in whom Pseudomonaswas dominant (35 patients) had an increased risk for all-cause mortality, with a hazard ratio of 3.12 (p = .0091). They also had more frequent exacerbations during follow-up compared to patients with other dominant genera.
The authors noted that the mechanism by which microbiome diversity might affect bronchiectasis requires further study. One possibility relates to antibiotic exposure, however – repeated exposure can lower diversity, and is thus a “plausible” mechanism behind the connection.
“Our analysis suggests the need for further studies to characterise different endotypes of bronchiectasis exacerbations and research to understand the mechanisms of reduced microbiome diversity and to explore how the microbiome could be modulated therapeutically,” the authors concluded.