Abstract

RATIONALE:Recent studies have revealed that in critically ill patients, lung microbiota are altered and correlate with alveolar inflammation. The clinical significance of altered lung bacteria in critical illness is unknown. OBJECTIVES:To determine if clinical outcomes of critically ill patients are predicted by features of the lung microbiome at the time of admission. METHODS:We performed a prospective observational cohort study in an intensive care unit (ICU) at a university hospital. Lung microbiota were quantified and characterized using droplet digital PCR and bacterial 16S rRNA gene sequencing. Primary predictors were the bacterial burden, community diversity, and community composition of lung microbiota. The primary outcome was ventilator-free days, determined at 28 days post admission. MEASUREMENTS AND MAIN RESULTS:Lungs of 91 critically ill patients were sampled using miniature-bronchoalveolar lavage within 24 hours of ICU admission. Patients with increased bacterial lung bacterial burden had fewer ventilator-free days (HR 0.43, CI 0.21-0.88), which remained significant when controlled for pneumonia and severity of illness. The community composition of lung bacteria predicted ventilator-free days (P=0.003), driven by the presence of gut-associated bacteria (e.g. Lachnospiraceae and Enterobacteriaceae spp.). Detection of gut-associated bacteria was also associated with the presence of the acute respiratory distress syndrome. CONCLUSIONS:Key features of the lung microbiome (bacterial burden, enrichment with gut-associated bacteria) predict outcomes in critically ill patients. The lung microbiome is an understudied source of clinical variation in critical illness, and represents a novel therapeutic target for the prevention and treatment of acute respiratory failure.