Abstract

Bronchiectasis has traditionally been viewed as a chronic airway disease driven primarily by persistent bacterial infection and neutrophilic inflammation. Advances in microbiome research suggest that airway dysbiosis, characterized by reduced microbial diversity and depletion of commensal organisms, is associated with disease progression. Culture-independent analyses reveal that bronchiectatic airways harbor polymicrobial communities, in which ecological imbalance often correlates more strongly with clinical outcomes than the presence of individual pathogens. Emerging evidence indicates that depletion of commensal taxa such as Prevotella, Veillonella, and Rothia mucilaginosa is associated with reduced antiinflammatory signaling, potentially contributing to an environment permissive of neutrophilic activation and protease-mediated tissue injury, although causal relationships remain unestablished. Disruption of the gut-lung axis may further amplify pulmonary inflammation by reducing circulating short-chain fatty acids and increasing systemic exposure to lipopolysaccharides. This review discusses the evolving concept of bronchiectasis as a potential disorder of microbial ecosystem imbalance. It examines therapeutic implications, including evidence from the phase 3 ASPEN trial supporting brensocatib as a neutrophiltargeted therapy, the role of long-term macrolide therapy, and emerging microbiome-directed strategies. The potential role of nutritional modulation through the gut-lung axis is discussed as a hypothesisgenerating area. Integrating microbial endotyping into clinical practice may support precision medicine strategies focused on restoring microbial homeostasis.

Keywords:Bronchiectasis; Dysbiosis; Lung microbiome; Gut-lung axis; Lipopolysaccharides; Dietary fiber; Short-chain fatty acids; Neutrophil extracellular traps; Brensocatib; Macrolides; Precision medicine