[Animal Experiment]-Oxygen therapy damages the lung microbiome of mice

  One of the symptoms of severe COVID-19 is shortness of breath, which can greatly reduce blood oxygen levels. This is called hypoxemia. After admission, these patients were given oxygen therapy to restore their levels to normal. However, new research suggests that this universal remedy may be passed unexpectedly. "People think the lungs are relatively clean and free of bacteria."

  UM Medical School's former postdoctoral researcher Shanna Ashley said. "It turns out that the balance of bacteria in the lungs is as important as the gut," Ashley worked with a team led by Dr. Robert Dixon, assistant professor of lung and critical care medicine and microbiology and immunology. His laboratory has spent many years studying the role of lung microbes in health and disease. Their research found that oxygen disrupted this balance and caused lung damage.

  Scientists have long known that oxygen can damage the lungs. Dixon said: "Oxygen is actually an effective lung toxin." "If a healthy mouse takes in 100% oxygen, it will die within 5 days and suffer from COVID-19 and other lungs. Torture of toxins. Like trauma patients, the lungs are severely injured."

  Intensive treatment patients usually require long-term high-concentration oxygen therapy. Their team began to study how therapeutic oxygen affects the lung microbiome. They studied critically ill patients who used a ventilator for more than 24 hours, and studied the bacteria detected in lung samples. They found that there were significant differences in the types of bacteria present in patient samples, depending on whether the bacteria received low, medium or high concentrations of oxygen. Specifically, patients receiving high oxygen levels are highly antioxidant bacteria and are more likely to grow Staphylococcus aureus, a common cause of lung infections in the ICU.

  Dixon said: "I want to know whether the oxygen I provide to patients affects the bacterial community in the respiratory tract, because different types of bacteria treat oxygen in very different ways."

  To understand the relationship between oxygen and lung bacteria, the research team designed a series of experiments in mice. They first exposed healthy mice to high concentrations of oxygen and studied the effect of oxygen on lung bacteria in healthy mice. Ashley said: "As expected, providing high levels of oxygen to healthy mice will quickly change the lung community." "Aerobes decrease and aerobic bacteria increase." After 3 days of oxygen therapy, aerobic grapes Cocci are by far the most common bacteria in mouse lungs.

  Next, the research team designed an experiment to answer the important question of "chicken or egg". Will these changes in the bacterial community cause lung damage? Or is it changing the bacterial community due to lung damage? First compare the lungs. Compared with changes in lung bacteria, the relative onset time of injury solves this problem.

  Using mice, it is possible to prove that due to the high oxygen concentration, the lung microbiome changed after 1 day, but it was not until 3 days later that the damage to the lungs was discovered, and the damage to the lungs after the microbiome was destroyed. Not another one. road. In addition, they showed that in mice exposed to oxygen, natural changes in lung bacteria are closely related to changes in the severity of inflammation. To further strengthen the causality, they turned to sterile mice lacking microbiota. "We wanted to see the advantages or disadvantages of being selective for the lungs of sterile bacteria exposed to therapeutic oxygen," Ashley said. Compare two groups of genetically identical mice. One group has bacteria and the other group does not. The bacteria-free mice are protected from oxygen-induced lung injury.