Longitudinal analysis of lung microbiome, immune response, and metabolism in ventilator-associated pneumonia: a cohort study

Rationale: Ventilator-associated pneumonia (VAP) is a common complication in patients under invasive mechanical ventilation (IMV), yet its underlying mechanisms remain poorly understood. This study investigated the lung microbiome, inflammatory response, and metabolism in patients undergoing IMV to identify factors that may predispose them to developing VAP. Objectives: To investigate how changes in lung microbiome composition, inflammatory response, and metabolic profiles may predispose patients undergoing IMV to develop VAP. Methods: Patients requiring IMV for at least 48 h due to non-infectious respiratory failure were enrolled. Bronchoalveolar lavage (BAL) samples were collected at baseline, upon VAP diagnosis, or after 72 h for non-VAP cases. DNA sequencing, cytokine quantification, and metabolomic analyses were performed. Results: Of the 80 patients, 41 (51%) developed VAP. No significant differences in alpha or beta diversity of the lung microbiome were observed between groups. However, both groups showed changes in microbiome composition over time, suggesting an impact of IMV. Tumour necrosis factor-alpha (TNF-α) lung levels were significantly higher in VAP patients, while lung interleukin-1 beta (IL-1β) increased in all patients. Metabolomic analysis revealed shifts in pentose phosphate and citric acid cycle pathways, indicating a transition to anaerobic metabolism in the lungs of VAP patients. Conclusions: Mechanical ventilation was associated with temporal changes in lung microbiome composition independent of VAP development. VAP cases exhibited higher TNF-α levels and metabolic profiles indicative of anaerobic adaptation, while IL-1β elevations were primarily linked to mechanical ventilation rather than infection.