oxygen therapy could affect lung microbiome

One of the hallmarks of severe COVID-19 is shortness of breath and significantly reduced levels of oxygen in the blood, called hypoxemia. Upon hospitalization, these patients are administered oxygen in an attempt to bring their levels back up to normal. However, a new study hints that this universal therapy may have unintended consequences via an unexpected source—the microbiome.

"It had been assumed that the lungs were relatively clean and free of bacteria,"

"We now know that the balance of bacteria inside the lungs matters much like it does in the gut."

Their work has found that oxygen disrupts this balance, contributing to lung injury.

Scientists have long known that oxygen can damage the lungs. "Oxygen is actually a potent lung toxin," says Dickson. "If I put healthy mice in 100% oxygen, they will die in five days, and they'll have the same kind of severe lung injury that patients with COVID-19 or other lung damage have."

They found marked differences in the bacteria species present in samples from patients depending on whether they received low, intermediate, or high concentrations of oxygen. Specifically, patients who received high oxygen concentrations were much more likely to grow Staphylococcus aureus, bacteria that are very oxygen-tolerant and a common cause of lung infections in the ICU.

The team next designed experiments to answer a key "chicken or the egg" question: do these altered bacterial communities contribute to lung injury? Or are bacterial communities altered because the lung is injured? They first addressed this by comparing the relative timing of changes in lung bacteria as compared to the onset of lung injury.

Using mice, they were able to demonstrate that while the lung microbiome was changed by high oxygen concentrations after only a day, lung injury wasn't detectable until after 3 days, proving that damage to the lung followed the disruption of the microbiome, and not the other way around

To further strengthen the causal link, they turned to germ-free mice, which completely lack a microbiome. "We wanted to see whether there was a selective advantage or disadvantage to having bacteria-free lungs when exposed to therapeutic oxygen," says Ashley. When comparing two groups of genetically identical mice—one with bacteria and one without—the mice without bacteria were protected from oxygen-induced lung injury.

"That was an extraordinary finding for us,"

Critically ill patients receiving oxygen are typically administered antibiotics as well. The team wondered: Could antibiotics alter the severity of oxygen-induced lung injury in mice? "The short answer is yes, we can affect the severity, but it wasn't in the direction we predicted," says Dickson. Vancomycin, an antibiotic that targets gram-positive bacteria like Staphylococcus, had no effect on lung injury, while ceftriaxone, a gram-negative antibiotic, made things worse.

"The microbiome is not all good and not all bad," comments Dickson. "That's why it's important for us to figure out the mechanisms here. We're currently using very non-specific interventions, when what we need is targeted manipulation of the microbiome."

 

 

 

reference

S.L. Ashley el al., "Lung and gut microbiota are altered by hyperoxia and contribute to oxygen-induced lung injury in mice," Science Translational Medicine (2020). stm.sciencemag.org/lookup/doi/ … scitranslmed.aau9959