Sodium Butyrate Reinforces Intestinal Homeostasis and Ameliorates Post-Resuscitation Neuroinflammation in Rat Model of Cardiac Arrest

Cardiac arrest (CA) poses a critical global public health challenge, with post-cardiac arrest syndrome (PCAS) remaining a leading cause of mortality despite advancements in resuscitation protocols. Systemic ischemia-reperfusion injury post-CA often triggers acute gastrointestinal injury (AGI), characterized by intestinal barrier disruption, dysbiosis, and endotoxin-driven inflammation, which correlates with poor clinical outcomes. This study investigated sodium butyrate, a gut microbiota-derived short-chain fatty acid, in a CA/CPR rat model, revealing its multifaceted therapeutic potential: it improved neurobehavioral recovery, preserved ileal epithelial tight junction integrity, and remodeled gut microbiota by enriching SCFA-producing taxa while suppressing pathogens. Furthermore, sodium butyrate significantly reduced neuroinflammatory markers (IL-1α, NLRP3 inflammasome) in brain tissues, suggesting modulation of the microbiota-gut-brain axis (MGBA). These findings underscore sodium butyrate’s role in mitigating PCAS through dual mechanisms—restoring intestinal homeostasis and dampening systemic inflammation—thereby offering a novel therapeutic strategy to improve post-resuscitation outcomes.