Ketogenic diet is protective during endotoxin-induced lung injury through the elevation of BHB

Acute respiratory distress syndrome (ARDS) is a severe condition characterized by severe pulmonary edema and hypoxia, affecting many individuals annually, particularly those in critical care or with septic shock. Researchers have previously suggested that a ketogenic diet, which is high in fat and low in carbohydrates, can influence inflammatory responses. However, the effects of this diet on septic ARDS outcomes remain unclear.

In a new study, researchers showed that mice fed a ketogenic diet exhibited significantly less lung injury and inflammation compared to mice on a standard diet during a murine model of endotoxin-induced lung injury. This model was induced by injecting intratracheal lipopolysaccharide (LPS). Utilizing immune mass cytometry studies on lung tissue, the team observed that the ketogenic diet decreased immune cell infiltration.

To explore the potential therapeutic benefits further, researchers administered beta-hydroxybutyrate (BHB), the primary metabolite of ketogenesis, to mice following the onset of ARDS. The treatment resulted in reduced pulmonary edema, lung inflammation, and NF-kB activity, indicating strong therapeutic potential. Additionally, multiplex analysis of bronchial alveolar lavage fluid revealed that both the ketogenic diet and BHB administration diminished the chemotaxis and activation of immune cells.

In conclusion, the findings suggest that the ketogenic diet offers protection to the lungs during endotoxin-induced lung injury by elevating BHB levels.