Lower Respiratory Microbiome Dysbiosis Is Associated With Poor Prognosis in Acute Severe Lower Respiratory Tract Infection

ABSTRACT

Acute severe lower respiratory tract infections (asLRTIs) pose a significant clinical challenge, especially in critically ill patients, but the role of the lower respiratory tract microbiome (LRTM) remains unclear. This study aimed to characterize LRTM composition and host immune factors to identify prognostic features of clinical outcomes. The study included 53 asLRTI patients and 35 controls. Metagenomics, metabolomics, proteomics, and RNA sequencing were conducted, while analysis of similarities (ANOSIM) and Cox regression were performed for statistics. Clinical data, including pneumonia severity scores, were collected on BALF sampling, with a 100‐day follow‐up. LRTM samples were grouped into five clusters (C1–C5). Cluster C5 resembled controls, while others showed significantly lower diversity. LRTM composition correlated with prognosis, with higher pathogenic bacteria abundance linked to poorer outcomes. Cluster C3 was associated with poor prognosis and reduced survival. Metabolite analysis revealed elevated α‐ketoisocaproic acid in asLRTIs and higher 10‐nitrolinoleate in poor‐prognosis patients. Immune responses varied across clusters, with distinct gene and cytokine expression patterns. Cluster C1, associated with Acinetobacter baumannii , exhibited heightened IL17 pathway activation. LRTM composition in asLRTIs is linked to clinical outcomes, with no single gradient of difference but distinct community states characterized by varying pathogens, metabolites, and immune responses.