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Updated: Dec 2, 2025
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Characterizing Salmonella Typhimurium-induced Septic Peritonitis in Mice
Published on: July 29, 2022
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Transcriptomic responses from improved murine sepsis models can better mimic human surgical sepsis
Philip A Efron1, Dijoia B Darden1, Zhongkai Wang2
1Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USA.
Summary
A new surgical sepsis model in mice better mimics human sepsis gene expression, unlike older models. This advance improves preclinical research for surgical sepsis, aiding human patient outcomes.
Area of Science:
- Biomedical Research
- Inflammation and Immunology
- Genomics and Transcriptomics
Background:
- Murine models of inflammation historically show poor correlation with human genomic expression in blood leukocytes.
- Previous sepsis models failed to accurately recapitulate human sepsis at the transcriptomic level.
- An improved cecal ligation and puncture (CLP) model with daily chronic stress (DCS) was developed, adhering to Minimum Quality Threshold in Pre-Clinical Sepsis Studies (MQTiPSS) guidelines.
Purpose of the Study:
- To determine if the improved murine surgical sepsis model (CLP with DCS) replicates human surgical sepsis transcriptomic patterns in blood leukocytes.
- To compare the transcriptomic similarity of the new murine model with human surgical sepsis and community-acquired sepsis.
- To assess the utility of improved preclinical models for understanding and treating human sepsis.
Main Methods:
- Utilized an improved murine surgical sepsis model (cecal ligation and puncture with daily chronic stress).
- Performed genome-wide expression analysis of circulating blood leukocytes in septic mice and human patients.
- Compared transcriptomic data between the murine model and human sepsis cohorts (surgical and community-acquired).
Main Results:
- The improved murine model demonstrated closer genome-wide expression patterns to human surgical sepsis patients, especially in chronic phases.
- Transcriptomic profiles from the new murine model did not align well with human community-acquired sepsis.
- Phenotypic similarities observed in the model were replicated at the transcriptomic level for surgical sepsis.
Conclusions:
- Improved preclinical murine sepsis models, like CLP with DCS, can better replicate human surgical sepsis phenotypes and transcriptomes.
- These advanced models show promise for improving research into surgical sepsis but are not suitable for studying other sepsis etiologies.
- Enhanced murine models can complement human-focused and AI-driven research to reduce sepsis morbidity and mortality.
