Abstract
BackgroundThe lung microbiome maintains the homeostasis of the immune system within the lungs. In acute respiratory distress syndrome (ARDS), the lung microbiome is enriched with gut-derived bacteria; however, the specific microbiome associated with morbidity and mortality in patients with ARDS remains unclear. This study investigated the specific patterns of the lung microbiome that are correlated with mortality in ARDS patients.MethodsWe analyzed the lung microbiome from the bronchoalveolar lavage fluid (BALF) of patients with ARDS and control subjects. We measured the copy numbers of 16S rRNA and the serum and BALF cytokines (interleukin [IL]-6, IL-8, receptor for advanced glycation end products, and angiopoietin-2).ResultsWe analyzed 47 mechanically ventilated patients diagnosed with (n = 40) or without (n = 7; control) ARDS. The alpha diversity was significantly decreased in ARDS patients compared with that of the controls (6.24 vs. 8.07, P = 0.03). The 16S rRNA gene copy numbers tended to be increased in the ARDS group compared with the controls (3.83 × 106 vs. 1.01 × 105 copies/mL, P = 0.06). ARDS patients were subdivided into the hospital survivor (n = 24) and non-survivor groups (n = 16). Serum IL-6 levels were significantly higher in the non-survivors than in the survivors (567 vs. 214 pg/mL, P = 0.027). The 16S rRNA copy number was significantly correlated with serum IL-6 levels in non-survivors (r = 0.615, P < 0.05). The copy numbers and relative abundance of betaproteobacteria were significantly lower in the non-survivors than in the survivors (713 vs. 7812, P = 0.012; 1.22% vs. 0.08%, P = 0.02, respectively). Conversely, the copy numbers of Staphylococcus, Streptococcus and Enterobacteriaceae were significantly correlated with serum IL-6 levels in the non-survivors (r = 0.579, P < 0.05; r = 0.604, P < 0.05; r = 0.588, P < 0.05, respectively).ConclusionsThe lung bacterial burden tended to be increased, and the alpha diversity was significantly decreased in ARDS patients. The decreased Betaproteobacteria and increased Staphylococcus, Streptococcus and Enterobacteriaceae might represent a unique microbial community structure correlated with increased serum IL-6 and hospital mortality.Trial registrationThe institutional review boards of Hiroshima University (Trial registration: E-447-4, registered 16 October 2019) and Kyoto Prefectural University of Medicine (Trial registration: ERB-C-973, registered 19 October 2017) approved an opt-out method of informed consent.
Highlights
Acute respiratory distress syndrome (ARDS) is a fatal disease that causes severe injury to alveolar epithelial cells and subsequent severe respiratory failure due to lung fibrosis, which results in high mortality rates of up to 40%
In acute respiratory distress syndrome (ARDS) patients with sepsis, bacteria in the gastrointestinal tract become enriched in the lower respiratory tract (LRT) [11], suggesting that interactions occur between the LRT and the gastrointestinal tract
Decreased diversity in bronchoalveolar lavage fluid (BALF) microbiotas in ARDS nonsurvivors To analyze the microbiota in the BALF, we performed 16S rRNA gene amplicon sequencing using next-generation sequencing (NGS)
Summary
Acute respiratory distress syndrome (ARDS) is a fatal disease that causes severe injury to alveolar epithelial cells and subsequent severe respiratory failure due to lung fibrosis, which results in high mortality rates of up to 40%. 10% of patients admitted to intensive care units (ICUs) are reported to have ARDS [1]. In ARDS patients with sepsis, bacteria in the gastrointestinal tract become enriched in the lower respiratory tract (LRT) [11], suggesting that interactions occur between the LRT and the gastrointestinal tract. Analysis of the lung microbiota in patients with trauma showed that ARDS occurrence was associated with increased Enterobacteriaceae [12]. The specific microbiome in the LRT related to morbidity and mortality in the LRT of ARDS patients remains unclear. In acute respiratory distress syndrome (ARDS), the lung microbiome is enriched with gut-derived bacteria; the specific microbiome associated with morbidity and mortality in patients with ARDS remains unclear. This study investigated the specific patterns of the lung microbiome that are correlated with mortality in ARDS patients
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