Lung Microbiome Found to Predict Outcomes in Critically Ill Patients

Key features of the lung microbiome (bacterial burden, enrichment with gut-associated bacteria) were found to predict outcomes in critically ill patients, representing a potential therapeutic target for the prevention and treatment of acute respiratory failure, according to study findings published in the American Journal of Respiratory and Critical Care Medicine.

Advances in culture-independent microbiology have shown in the past decade that lungs, previously considered sterile, contain complex and dynamic communities of bacteria. As researchers note, lung microbiota are detectable in health, altered in disease, and correlate with variation in airway and alveolar immunity. In a recent study, lung microbiota were found to contribute to the progression of idiopathic pulmonary fibrosis, in which microbiota diversity and composition correlate with increased alveolar profibrotic cytokines.

Similarly, the lung microbiota of critically ill patients are significantly altered compared with those of healthy subjects, correlating with alveolar and systemic inflammation. In patients with acute respiratory distress syndrome (ARDS), the lung microbiome is enriched with gut-associated bacteria, which serves as a biomarker for development of ARDS. “Altered lung microbiota may propel and perpetuate alveolar inflammation and injury among critically ill patients, but to date no study has determined whether altered lung microbiota predict disease outcomes in this population,” said the study authors.

Researchers aimed to determine whether lung microbiota at intensive care unit (ICU) admission predicts clinical outcomes in critically ill patients. Mini-BAL specimens, containing distinct bacterial signal from negative controls specimens, were obtained from 91 critically ill patients within 24 hours of their ICU admission, with the primary outcome of ventilator-free days. Researchers examined the association between ventilator-free days and the bacteria level present, and whether detection of gut-associated bacteria in the lung microbiome persisted.

Study results found that in patients with ARDS, the bacterial DNA burden in mini-BAL specimens was greater compared with patients without ARDS (P = .014). Patients with increased lung bacterial burden were shown to have fewer ventilator-free days (hazard ratio, 0.43; 95% CI, 0.21-0.88), which remained significant when controlled for pneumonia and severity of illness.

Researchers then compared the community composition of bacterial communities in ARDS and non-ARDS specimens and found that there was a detectable separation of specimens according to ARDS status. The collective difference, confirmed statistically via mvabund, was robust to taxonomic level of comparison (P = .014 at the OTU level of taxonomy; P = .013 at the family level; P = .003 at the phylum level).

When delineating what specific taxa were associated with poor outcomes, researchers identified the gut-associated Lachnospiraceae (P = .020) and Enterobacteriaceae (P = .12) families as the taxa most strongly predictive of fewer ventilator-free days, although Enterobacteriaceae was not statistically significant. Detection of gut-associated bacteria was also associated with the presence of ARDS.

Senior study author Lieuwe Bos, MD, PhD, researcher in pulmonology and critical care, stressed that the lung microbiome may represent a novel target for preventing and treating clinical illness. “We can’t change our patients’ genes or their chronic diseases, but we can potentially change their bodies’ microbiota," said Bos.

Study authors note that the next step in research will focus on determining whether modifying lung bacteria influences patients’ outcomes. “Knowing that immune function and the microbiome differ among these patients may not only help us predict our patients’ outcomes but to change them for the better,” said Bos.

Reference

Dickson RP, Schultz MJ, van der Poll T, et al. Lung microbiota predict clinical outcomes in critically ill patients [published online January 24, 2020]. Am J Respir Crit Care Med. doi: 10.1164/rccm.201907-1487OC.