Ketogenic diet is protective during endotoxin-induced lung injury through the elevation of BHB
- 1Department of Anesthesiology, Critical Care, and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston
Abstract
Acute respiratory distress syndrome (ARDS) is marked by severe pulmonary edema and concomitant hypoxia, affecting hundreds of thousands of people a year, especially those in critical care conditions or suffering from septic shock. Previous studies have implicated that the ketogenic diet, a high-fat and low-carbohydrate diet, modulates inflammatory responses. However, the impact of the ketogenic diet on septic ARDS outcomes is unknown. Here, we demonstrated that mice on a ketogenic diet showed strikingly reduced lung injury and inflammation compared to those on a control diet during a murine model of endotoxin-induced lung injury, induced by intratracheal lipopolysaccharide (LPS) injection. Immune mass cytometry studies on lung tissue indicated that the ketogenic diet reduces immune cell infiltration. Treating mice with beta-hydroxybutyrate (BHB), the primary metabolite of ketogenesis, after the onset of ARDS reduced pulmonary edema and lung inflammation, as well as NF-kB activity, suggesting strong therapeutic potential. By multiplex analysis in bronchial alveolar lavage fluid, we observed that the ketogenic diet or BHB administration attenuates the chemotaxis and activation of immune cells. Altogether, our findings reveal that the ketogenic diet provides lung protection during endotoxin-induced lung injury through BHB.
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BibTeX
@misc{lwanga2026ketogenic,
title = {{Ketogenic diet is protective during endotoxin-induced lung injury through the elevation of BHB}},
author = {R. lwanga and T. T. Tran and J. Kim and K. Figarella and K. Huang and W. Zhang and R. Nair and V. Guaregua and S. Phan and H. Canales and X. Chen and S. Horton and Y. A. An and X. Yuan},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.20.753061},
url = {https://www.biorxiv.org/content/10.64898/2026.09.20.753061v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Ketogenic diet is protective during endotoxin-induced lung injury through the elevation of BHB
AU - R. lwanga
AU - T. T. Tran
AU - J. Kim
AU - K. Figarella
AU - K. Huang
AU - W. Zhang
AU - R. Nair
AU - V. Guaregua
AU - S. Phan
AU - H. Canales
AU - X. Chen
AU - S. Horton
AU - Y. A. An
AU - X. Yuan
PY - 2026
DA - 2026/09/20
PB - bioRxiv
DO - 10.64898/2026.09.20.753061
UR - https://www.biorxiv.org/content/10.64898/2026.09.20.753061v1
AB - Acute respiratory distress syndrome (ARDS) is marked by severe pulmonary edema and concomitant hypoxia, affecting hundreds of thousands of people a year, especially those in critical care conditions or suffering from septic shock. Previous studies have implicated that the ketogenic diet, a high-fat and low-carbohydrate diet, modulates inflammatory responses. However, the impact of the ketogenic diet on septic ARDS outcomes is unknown. Here, we demonstrated that mice on a ketogenic diet showed strikingly reduced lung injury and inflammation compared to those on a control diet during a murine model of endotoxin-induced lung injury, induced by intratracheal lipopolysaccharide (LPS) injection. Immune mass cytometry studies on lung tissue indicated that the ketogenic diet reduces immune cell infiltration. Treating mice with beta-hydroxybutyrate (BHB), the primary metabolite of ketogenesis, after the onset of ARDS reduced pulmonary edema and lung inflammation, as well as NF-kB activity, suggesting strong therapeutic potential. By multiplex analysis in bronchial alveolar lavage fluid, we observed that the ketogenic diet or BHB administration attenuates the chemotaxis and activation of immune cells. Altogether, our findings reveal that the ketogenic diet provides lung protection during endotoxin-induced lung injury through BHB.
ER -