Time-restricted feeding protects against septic liver injury by reshaping gut microbiota and metabolite 3-hydroxybutyrate.
Summary
In murine sepsis models, time-restricted feeding protected the liver by reshaping gut microbiota and elevating the ketone body 3-hydroxybutyrate (3-HB). The study used germ-free and Hmgcs2/Lpin1 knockout mice, multi-omics, and hepatocyte experiments to implicate a microbiota–metabolite axis in mitigating septic liver injury.
Key Findings
- Time-restricted feeding (TRF) mitigated septic liver injury in mice.
- TRF reshaped gut microbiota and increased 3-hydroxybutyrate (3-HB).
- Mechanistic support came from germ-free and Hmgcs2/Lpin1 knockout mice plus multi-omics and hepatocyte assays.
Clinical Implications
Although preclinical, the data support evaluating time-restricted feeding paradigms or exogenous ketone/3-HB strategies as adjuncts to protect the liver in sepsis, while carefully considering ICU feasibility and nutrition risks.
Why It Matters
This work links dietary timing to sepsis organ protection via a defined microbiome–metabolite mechanism, offering testable immunometabolic targets (e.g., 3-HB) for translation.
Limitations
- Preclinical animal study; human generalizability is unknown.
- Feasibility and safety of time-restricted feeding in critically ill patients remain uncertain.
Future Directions
Pilot human studies to test ketone/3-HB supplementation and circadian-aligned feeding in sepsis, with microbiome and metabolomic endpoints.
Study Information
- Study Type
- Case-control
- Research Domain
- Pathophysiology
- Evidence Level
- V - Preclinical mechanistic study in mice and cells with multi-omics.
- Study Design
- OTHER