Introduction: Severe acute pancreatitis (SAP) is frequently complicated by intestinal barrier disruption, bacterial translocation, and systemic inflammation. Emerging evidence indicates that gut microbial metabolic disturbances, particularly altered short-chain fatty acids (SCFAs), may contribute to epithelial injury, yet the mechanistic links between microbial metabolites and host inflammatory signaling remain insufficiently defined. We therefore investigated whether Methods: A mouse model of SAP was established and animals received LP18 intervention. Intestinal injury and barrier integrity were evaluated by histopathology, tight junction protein assessment, and inflammatory cytokine measurements. Metabolic alterations were profiled using untargeted metabolomics and targeted quantification of SCFAs was performed. NF-κB signaling was assessed by measuring p65 phosphorylation and nuclear translocation. Correlation analyses were conducted to relate SCFA levels to barrier markers. Results: SAP induced pronounced epithelial injury, including villus atrophy, Tight junction disruption, elevated pro-inflammatory cytokines, and robust NF-κB activation. Untargeted metabolomics revealed extensive metabolic perturbations, with significant changes in butanoate metabolism and lipid-associated pathways. LP18 administration partially reversed these abnormalities and shifted the metabolomic profile toward a mucosa-protective signature. Targeted SCFA analysis showed marked butyrate depletion in SAP mice, whereas LP18 significantly increased butyrate levels and partially normalized acetate and propionate. Higher butyrate concentrations correlated with improved intestinal integrity and reduced inflammatory response. Mechanistically, LP18 suppressed inflammatory signaling by inhibiting p65 phosphorylation and nuclear translocation, consistent with attenuated NF-κB pathway activation. Conclusion: