Author ORCID Identifier

0009-0009-2140-5852

Date of Graduation

12-2025

Document Type

Thesis (MS)

Program Affiliation

Therapeutics and Pharmacology

Degree Name

Masters of Science (MS)

Advisor/Committee Chair

Dr. Xiaoyi Yuan

Committee Member

Dr. Holger Eltzschig

Committee Member

Dr. Yu (Aaron) An

Committee Member

Dr. Juli Bai

Committee Member

Dr. Wenbo Li

Abstract

Acute respiratory distress syndrome (ARDS) is a lung condition caused by uncontrolled lung inflammation with excessive immune cell infiltration, which eventually leads to severe pulmonary edema and poor oxygenation. ARDS affects hundreds of thousands of people a year, particularly those afflicted with sepsis or other critical illnesses. So far, there is a lack of effective therapeutic approaches for ARDS. Nutrition is a crucial part of managing critical illnesses, with the current focus on maintaining a sufficient caloric intake. However, the impact of dietary interventions such as the ketogenic diet remains poorly understood in septic ARDS. The ketogenic diet, characterized by a high-fat and low-carbohydrate content, has been shown to exhibit anti-inflammatory properties and satisfactory safety profiles in critically ill populations. Here, we demonstrated that mice maintained with a ketogenic diet showed dramatically 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. Utilizing a proteomic-based array, ion chromatography–mass spectrometry (IC-MS), and multiplex assays in bronchial alveolar lavage fluid, as well as immune mass cytometry studies on lung tissue, we discovered that the ketogenic diet attenuates immune cell chemotaxis. In addition, treating mice with beta-hydroxybutyrate (BHB), the primary metabolite of ketogenesis, before or after the onset of septic ARDS has also been shown to reduce pulmonary edema and lung inflammation, implying a potential molecular mechanism for the ketogenic diet-mediated lung protection. These findings display that the ketogenic diet provides lung protection during endotoxin-induced lung injury via reduced cell chemotaxis through BHB.

Keywords

Ketogenic diet, Acute respiratory distress syndrome, Endotoxin-induced, Lung injury, BHB

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Available for download on Saturday, December 05, 2026

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