A longitudinal characterization of the Non-Cystic Fibrosis Bronchiectasis airway microbiome

Abstract

A diverse microbiota exists within the airways of individuals with non-cystic fibrosis bronchiectasis (nCFB). How the lung microbiome evolves over time, and whether changes within the microbiome correlate with future disease progression is not yet known. We assessed the microbial community structure of 133 serial sputa and subsequent disease course of 29 nCFB patients collected over a span of 4–16 years using 16S rRNA paired-end sequencing. Interestingly, no significant shifts in the microbial community of individuals were observed during extended follow-up suggesting the microbiome remains relatively stable over prolonged periods. Samples that were Pseudomonas aeruginosa culture positive displayed markedly different microbial community structures compared to those that were positive for Haemophilus influenzae . Importantly, patients with sputum of lower microbial community diversity were more likely to experience subsequent lung function decline as defined by annual change in ≥−1 FEV 1 % predicted. Shannon diversity values <1 were more prevalent in patients with FEV 1 decline (P = 0.002). However, the relative abundance of particular core microbiota constituents did not associate with risk of decline. Here we present data confirming that the microbiome of nCFB individuals is generally stable, and that microbiome-based measurements may have a prognostic role as biomarkers for nCFB.

The microbiome in bronchiectasis

“…complex, contains multiple bacterial genera and is highly individual [46,47]. A recent longitudinal study by WOO et al [48] followed 29 bronchiectasis patients for up to 16 years and demonstrated remarkable stability of the microbiome over many years of follow-up. The microbiomes of Pseudomonas-and Haemophilus-dominated patients were widely divergent and patients maintained similar profiles over time despite antibiotic treatments [48].…”

“…A recent longitudinal study by WOO et al [48] followed 29 bronchiectasis patients for up to 16 years and demonstrated remarkable stability of the microbiome over many years of follow-up. The microbiomes of Pseudomonas-and Haemophilus-dominated patients were widely divergent and patients maintained similar profiles over time despite antibiotic treatments [48]. This is consistent with what has been seen with culture, where chronic infection with P. aeruginosa or H. influenzae often persists over many years regardless of therapy [49].…”

“…Several studies suggest that severe bronchiectasis is reduced with lower diversity of the microbiome measured by composite indices such as the Shannon diversity index [42]. WOO et al [48] demonstrated in their small study (n=29) that very low diversity values were associated with more rapid lung function decline.…”

The microbiome in bronchiectasis: Cutting a lung story short

“…While the small sample size of 21 is comparable in size to similar microbiome studies in bronchiectasis, this is unlikely to be sufficiently representative considering that bronchiectasis is a heterogeneous disease and affects millions of people worldwide. Moreover, microbiome characterization by 16S sequencing is not quantitative and the study did not include any measurement of bacterial load, which is strongly linked to lung inflammation and likely treatment response …”

“…comorbidities, viral/fungal infections and antibiotic treatment) resulting in a low signal-noise ratio; and (iii) lung function itself only weakly correlates with the severity of bronchiectasis and is often not responsive to deterioration or therapy. 10 While the small sample size of 21 is comparable in size to similar microbiome studies in bronchiectasis, 7,11 this is unlikely to be sufficiently representative considering that bronchiectasis is a heterogeneous disease and affects millions of people worldwide. Moreover, microbiome characterization by 16S sequencing is not quantitative and the study did not include any measurement of bacterial load, which is strongly linked to lung inflammation and likely treatment response.…”