Optimization of a fresh fecal intraperitoneal injection sepsis model and its divergent dynamics from cecal ligation and puncture in mice.

Abstract

Background: Sepsis remains a critical challenge in intensive care, necessitating reliable animal models that accurately mimic human pathophysiological responses. While cecal ligation and puncture (CLP) is widely considered the gold standard, its inherent variability often limits reproducibility. This study aimed to optimize a fecal intraperitoneal injection (FIP) murine model by evaluating the impact of fecal preparation (fresh vs. lyophilized) and dosage (0.5-1.0 g/kg) on model stability. We systematically compared the optimized FIP model with the conventional CLP method in male BALB/c mice to define their respective pathophysiological characteristics and suitability for therapeutic screening.

Results: Fresh fecal suspensions significantly enhanced model reproducibility compared to dried preparations, which exhibited inconsistent virulence. An optimized FIP dose of 0.7 g/kg induced a hyperacute sepsis phenotype, characterized by rapid systemic bacterial dissemination and severe acute organ damage within 24 h. Crucially, semi-quantitative histological scoring confirmed that FIP triggered a synchronized, hyperacute injury spike across the lung, kidney, liver, and heart, whereas the CLP model exhibited a more protracted, progressive exacerbation of organ dysfunction through 48 h. Hematological analysis further revealed that while both models induced systemic inflammation, the FIP model provided a much sharper and predictable onset of severe leukopenia and multi-organ failure.

Conclusions: The optimized FIP model, characterized by its procedural simplicity, high controllability, and superior reproducibility, serves as a robust platform for investigating the early, fulminant pathophysiological mechanisms of unmitigated sepsis. Conversely, the CLP model remains the preferred choice for studies focusing on protracted infection and chronic organ dysfunction. These findings provide a methodological framework for selecting appropriate sepsis models based on specific research objectives in experimental medicine.

Clinical trial number: Not applicable.