Co-occurring bronchoalveolar lavage fluid microbiota and inflammatory features across BSI-defined disease severity groups during acute exacerbations of non-cystic fibrosis bronchiectasis

Airway dysbiosis and inflammation characterize bronchiectasis, but their relationship with underlying disease severity during acute exacerbations remains unclear. We analyzed 135 adults hospitalized with acute exacerbations of non-cystic fibrosis bronchiectasis from a prospective single-center cohort. Bronchoalveolar lavage fluid (BALF) underwent shotgun metagenomic sequencing and inflammatory profiling. Participants were stratified by the Bronchiectasis Severity Index (BSI) as mild ( n = 27), moderate ( n = 37), or severe ( n = 71). Covariate-adjusted sensitivity analyses showed higher genus-level Pseudomonas and species-level Pseudomonas aeruginosa abundances in the severe group than in the mild and moderate groups (pairwise P adjusted ≤ 0.029) and lower Shannon diversity and Pielou evenness in the moderate and severe groups than in the mild group at both taxonomic levels (pairwise P adjusted ≤ 0.002), without moderate–severe differences in diversity. Community-level differences were modest (adjusted PERMANOVA marginal R ² = 0.021–0.024, P ≤ 0.020), and PERMDISP detected no significant dispersion differences. BALF inflammatory measures also varied across groups: IL-6 and IL-8 were higher in the moderate and severe groups than in the mild group ( P adjusted ≤ 0.020), and the neutrophil proportion was higher in the severe group than in the mild group ( P adjusted = 0.038). An exploratory inverse association was observed between species-level Pielou evenness and reported disease duration after multiplicity correction ( ρ = −0.320, P adjusted = 0.036). During acute exacerbations, BSI-defined bronchiectasis severity was associated with greater representation of Pseudomonas , particularly P. aeruginosa , within the BALF microbiota, reduced diversity and evenness, and differences in measured BALF cytokine concentrations and cellular composition. These co-occurring microbial and inflammatory features in BALF warrant longitudinal evaluation across clinical states to define their temporal dynamics and clinical relevance.