Lung damage from oxygen poisoning was associated with changes in the composition of bacterial communities of this organ. According to an article published in the journal Science Translational Medicine, at high concentrations of oxygen in the microbial composition of the lungs, there is a shift towards aerobic microorganisms, such as the pathogenic Staphylococcus aureus, which contribute to lung damage.
Inhalation of pure oxygen is widely used in the correction of acute and chronic hypoxemia — a reduced level of oxygen in the blood. However, hyperoxia — increased oxygen content in the inhaled air and, as a result, its increased partial pressure in the blood-causes fatal lung damage in animals, and in humans it is associated with increased mortality, severe lung damage and pneumonia. However, the mechanisms by which hyperoxia provokes diffuse inflammation and damage to the alveoli of the lungs remain poorly understood.
Scientists led By Shanna L. Ashley from the University of Michigan School of Medicine studied how the pulmonary microbiota changes during hyperoxia in mice and humans. First, they analyzed the lung microbiome of 1,523 seriously ill patients who were on artificial ventilation for more than a day. Patients were divided into groups according to the fraction of inhaled oxygen (FiO2): low (FiO2 from 21 to 46 per cent), medium (FiO2 from 43 to 55 per cent) and high (FiO2 more than 55 per cent) hyperoxia.
In patients with low FiO2 levels, the percentage of S. aureus and P. aeruginosa bacteria in airway secretions was 28.3 and 22.6 per cent, respectively. In contrast, respiratory samples of patients with high FiO2 produced twice as many S. aureus colonies when cultured compared to P. aeruginosa (35.9 vs. 14.9 per cent). A multivariate analysis, adjusted for gender, age, race, and treatment, found that the frequency of p. aeruginosa release was higher in patients receiving low and medium concentrations of FiO2 (8.6 and 7.6 per cent, respectively; p = 0.001 and p = 0.007, respectively). At the same time, the growth rate of S. aureus did not significantly differ in patients receiving mixtures with low, medium or high FiO2 (p > 0.05 for all comparisons). Thus, the scientists concluded that hyperoxia independently predicts the subsequent growth of bacteria in the lungs of seriously ill patients.
Acute hyperoxia also changed the composition of the bacterial community of the lung microbiota of adult mice (p = 0.0064). In hyperoxia, a rapid and persistent decrease in the relative abundance of anaerobic taxa was observed in mice. In contrast, the oxygen-tolerant Staphylococcus family increased after 72 hours of hyperoxia (p = 0.0007).
When comparing the relative terms of violation of the lung microbiota when exposed to oxygen, it turned out that changes in bacterial composition began after 24 hours of hyperoxia (p = 0.0001), and detectable lung damage was determined only after 72 hours (p = 0.0001). The scientists concluded that dysbacteriosis of the pulmonary microbiota caused by increased oxygen content preceded the appearance of detectable lung damage, indicating that the change in the lung microbiome was not a consequence of lung damage.
As previously reported, pulmonary concentrations of TNF-α and interleukin-17 increase in proportion to the time of hyperoxia. After 48 hours of hyperoxia, both cytokines were inversely correlated with microbial composition (p = 0.0013 for TNF-α and p = 0.0012 for interleukin-17). However, no taxonomic group was responsible for the correlation between lung bacterial communities and cytokine concentrations, indicating a complex effect of the community rather than a direct effect of a single bacterial species.
Hyperoxia also had a significant effect on the composition of the intestinal bacterial community (p = 0.005), although a statistically significant effect was only apparent after 72 hours of oxygen exposure (p = 0.001). Moreover, changes in the microbial composition of intestinal bacteria were positively correlated with lung inflammation 48 hours after exposure to oxygen (p = 0.0039 for TNF-α and p = 0.0008 for interleukin-17).
In mice with normal microbiota, high oxygen concentrations provoked diffuse damage to the lung alveoli with an increase in the concentration of alveolar protein after 72 hours (p = 0.0018). The lungs of gnotobiotic mice exposed to hyperoxia contained significantly less alveolar protein than the lungs of mice with normal microbiota (P < 0.0001).
After 96 hours of hyperoxia, the lungs of mice with normal microbiota showed signs of acute lung damage, including diffuse epithelial necrosis with hyaline membranes. In contrast, the lungs of gnotobiotic mice retained their alveolar structure and showed no signs of epithelial damage or hyaline membrane formation. These results confirmed that gnotobiotic mice were protected from oxygen-induced lung damage.
This work shows that the pulmonary microbiota, which changes during hyperoxia, contributes to the pathogenesis of oxygen damage to the lungs in mice. A better understanding of the role of oxygen in microbial homeostasis and its violation will allow changing the composition of the microbiota of the lungs and intestines for the prevention and treatment of oxygen-induced lung damage.
Photos: S. L. Ashley et al. / Science Translational Medicine, 2020