Prophylactic Short-Chain Fatty Acid Supplementation Modulates Circulating Immunometabolic Biomarkers and Reduces Organ-Injury Markers in CLP-Induced Sepsis

Background: Sepsis involves profound immune and metabolic disturbances. This study investigated whether prophylactic short-chain fatty acid (SCFA) supplementation alters circulating immunometabolic biomarkers and biochemical markers of hepatic and renal injury in experimental sepsis.Methods: Male Wistar rats were assigned to four groups (n = 12/group) with independent 24-h and 48-h subgroups. Sepsis was induced by cecal ligation and puncture (CLP). A mixture of sodium acetate, propionate, and butyrate (60:20:20 molar ratio; total dose 500 mg/kg) was administered intraperitoneally for 7 days before CLP and discontinued after sepsis induction. Circulating immunometabolic and organ-injury-related markers were measured.Results: SCFA supplementation increased circulating G protein-coupled receptor 41 (GPR41)- and G protein-coupled receptor 43 (GPR43)-related marker concentrations and produced an overall increase in glucagon-like peptide-1 (GLP-1). Angiopoietin-like protein 4 (ANGPTL4) increased significantly in septic animals at both time points, whereas C1q/tumor necrosis factor-related protein 3 (CTRP3) was not significantly altered by SCFA supplementation within septic animals. Circulating NOD-like receptor family pyrin domain-containing protein 3 (NLRP3)-related marker concentrations were reduced at 24 h and 48 h, while NLRP6-related marker concentrations were reduced at 48 h. SCFA supplementation also reduced alanine aminotransferase (ALT), urea, and creatinine at both time points and aspartate aminotransferase (AST) at 48 h. Other adipokine and metabolic marker responses were marker- and time-dependent.Conclusion: Prophylactic SCFA supplementation was associated with changes in circulating immunometabolic biomarkers and reductions in biochemical markers of hepatic and renal injury in CLP-induced sepsis. These findings require further tissue-based and therapeutic investigation.