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, in a new study, researchers found that this universal therapy may have unintended consequences via an unexpected source—the microbiome.
The research was conducted by a team at the University of Michigan.
It had been assumed that the lungs were relatively clean and free of bacteria.
But scientists now know that the balance of bacteria inside the lungs matters much as it does in the gut.
Scientists have long known that oxygen can damage the lungs.
The team says healthy mice are put 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.
Patients in intensive care are often treated with high concentrations of oxygen for long periods of time. The team began to explore how therapeutic oxygen was affecting the lung microbiome.
They looked at critically ill patients who were on a ventilator for more than 24 hours and studied bacteria detected in specimens from their lungs.
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.
To better understand the relationship between oxygen and lung bacteria, the team designed a series of experiments in mice.
They found when they gave high concentrations of oxygen to healthy mice, their lung communities changed quickly, and just as predicted. The oxygen-intolerant bacteria went down, and the oxygen-tolerant bacteria went up.
After three days of oxygen therapy, oxygen-tolerant Staphylococcus was by far the most commonly detected bacteria in mouse lungs.
The team next designed experiments to see if these altered bacterial communities contribute to lung injury, or are bacterial communities altered because the lung is injured.
They found 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.
To further strengthen the causal link, they turned to germ-free mice, which completely lack a microbiome.
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.
The team says critically ill patients receiving oxygen are typically administered antibiotics as well. Antibiotics could alter the severity of oxygen-induced lung injury.
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.
This study provides important insights into the contributions of the microbiome toward inflammation and damage in the lungs exposed to varying levels of oxygen.
One author of the study is Shanna Ashley, Ph.D.
The study is published in Science Translational Medicine.
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