Intestinal Lactate Supports Epithelial Renewal During Sepsis
Overview
This study demonstrates that sepsis induces metabolic reprogramming in intestinal epithelial cells, resulting in decreased intestinal lactate levels despite elevated serum lactate. Lactate supplementation via gavage in septic mice improved intestinal morphology and showed a trend toward increased survival.
Background
Sepsis is a critical condition characterized by dysregulated host responses to infection, frequently causing acute gastrointestinal injury. Intestinal stem cells rely on lactate for proliferation, yet sepsis suppresses their renewal. Understanding the role of lactate in intestinal epithelial cell dynamics during sepsis may reveal novel therapeutic targets.
Data Highlights
Parameter
Control (Sham)
CLP (Sepsis)
Intestinal Lactate Level
Higher
Lower at 6h and 24h
Serum Lactate Level
Lower
Higher
Pyruvate Dehydrogenase Expression
Baseline
Increased
Lactate Dehydrogenase Expression
Baseline
Decreased
6-Phosphogluconate & Phosphoenolpyruvate Levels
No difference
No difference
Citric Acid Level
Baseline
Slightly increased
Survival Trend with Lactate Gavage
Not applicable
Slight increase
Intestinal Length
Longer
Shorter, improved with lactate
Villus Length
Longer
Shorter, increased with lactate
Key Findings
Sepsis induced by cecal ligation and puncture (CLP) decreases intestinal lactate levels but increases serum lactate.
Transcriptome analysis reveals increased pyruvate dehydrogenase and decreased lactate dehydrogenase expression in intestinal tissue during sepsis, indicating metabolic reprogramming.
Levels of 6-phosphogluconate and phosphoenolpyruvate remain unchanged, while citric acid slightly increases in septic intestinal tissue.
Lactate gavage for 7 days in CLP mice trends toward improved survival and significantly increases intestinal length and villus height.
Lactate supplementation may promote intestinal epithelial cell renewal and mitigate sepsis-induced intestinal damage.
Clinical Implications
These findings suggest that targeting intestinal lactate metabolism could be a promising therapeutic approach to protect and restore intestinal epithelial integrity in septic patients. Lactate supplementation may enhance epithelial renewal and improve gut barrier function, potentially reducing sepsis-related complications. Further research is needed to clarify mechanisms and optimize treatment strategies.
Conclusion
Intestinal lactate plays a critical role in epithelial cell renewal during sepsis, and its supplementation shows potential to improve intestinal morphology and survival outcomes. This highlights lactate as a candidate for therapeutic intervention in sepsis-induced gastrointestinal injury.
References
Singer et al. 2016 -- The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)
Li et al. 2019 -- Acute Gastrointestinal Injury in Sepsis
Zhang et al. 2020 -- Lactate Metabolism in Intestinal Stem Cells
Wang et al. 2021 -- Intragastric Lactate Enhances Intestinal Renewal
Liu et al. 2023 -- Lactate Regulates Cell Cycle via Protein Remodeling
