Altered lung microbiota profiles are associated with disease severity, exacerbation frequency and neutrophilic inflammation in bronchiectasis

Rationale: We investigated the microbiome of 133 clinically stable patients with bronchiectasis to determine the relationship of microbiota profiles with disease severity and clinical outcomes.

Methods: 133 bronchiectasis patients enrolled in a prospective observational cohort study in a single UK centre provided sputum samples whilst clinically stable. The microbiota profile (Shannon-Weiner Diversity Index and predominant genera) of each patient, as determined by 16s rRNA sequencing on the Illumina MiSeq platform and sequence analysis in Qiime, was compared to exacerbation frequency and the Bronchiectasis Severity Index (BSI). Markers of neutrophilic lung inflammation (myeloperoxidase, elastase) and cytokines were measured in spontaneous sputum.

Results: The mean age of the patients was 64 years, 60% were female and 50% had idiopathic bronchiectasis. The microbiome of bronchiectasis patients was heterogeneous; some dominated by genera such as Haemophilus or Pseudomonas whilst other patients had a diverse microbiome with a combined predominance of Veillonella, Prevotella and Leptotrichia. A lower Shannon-Weiner Diversity Index was associated with multiple markers of disease severity including a higher BSI (P= 0.0003) and more frequent exacerbations (P= 0.008). Lower diversity or having a microbiota dominated with Haemophilus, Pseudomonas or Enterobacteriaceae sp. was significantly associated with higher levels of sputum myeloperoxidase and elastase (Figure) but not with Interleukin-1β or Interleukin-8.