Research ArticleMICROBIOTA

Lung and gut microbiota are altered by hyperoxia and contribute to oxygen-induced lung injury in mice

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Science Translational Medicine  12 Aug 2020:
Vol. 12, Issue 556, eaau9959
DOI: 10.1126/scitranslmed.aau9959

Linking hyperoxia to microbial dysbiosis

Inhaled oxygen is a commonly administered therapy that causes severe lung injury in animals and is associated with poor clinical outcomes in humans. The bacteria that live within the body’s lungs and gut are highly variable in their tolerance of oxygen. Ashley et al. now report that in both humans and mice, inhaled oxygen influenced respiratory bacterial communities. In mice, variations in lung and gut bacterial communities correlated with the severity of lung injury, and germ-free mice were protected from oxygen-induced lung injury. These results suggest that the bacteria of our lungs and gut play an important role in the pathogenesis of oxygen-induced lung injury.

Abstract

Inhaled oxygen, although commonly administered to patients with respiratory disease, causes severe lung injury in animals and is associated with poor clinical outcomes in humans. The relationship between hyperoxia, lung and gut microbiota, and lung injury is unknown. Here, we show that hyperoxia conferred a selective relative growth advantage on oxygen-tolerant respiratory microbial species (e.g., Staphylococcus aureus) as demonstrated by an observational study of critically ill patients receiving mechanical ventilation and experiments using neonatal and adult mouse models. During exposure of mice to hyperoxia, both lung and gut bacterial communities were altered, and these communities contributed to oxygen-induced lung injury. Disruption of lung and gut microbiota preceded lung injury, and variation in microbial communities correlated with variation in lung inflammation. Germ-free mice were protected from oxygen-induced lung injury, and systemic antibiotic treatment selectively modulated the severity of oxygen-induced lung injury in conventionally housed animals. These results suggest that inhaled oxygen may alter lung and gut microbial communities and that these communities could contribute to lung injury.

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