Protective Effects of Clostridium sporogenes Intervention on Acute Liver Injury in Mice

In this study, we established a mouse model of acute liver injury using CCl4 and found that prophylactic treatment with C. sporogenes or its supernatant conferred protective effects against liver injury and inflammation. Non-targeted metabolomics analysis of fecal samples from mice treated with C. sporogenes and its supernatant revealed significant enrichment in pathways related to amino acid synthesis and degradation. Differential metabolite analysis identified 5-aminovaleric acid (5-AVA), a metabolite consistently upregulated across both metabolomic datasets, as a potential effective metabolite contributing to the hepatoprotective effects of C. sporogenes. Notably, 5-AVA was found to inhibit M1 polarization of macrophages in vitro, and transcriptomic analysis highlighted the key regulatory pathway involved, namely the NFKB pathway. These findings suggest that C. sporogenes inhibit M1 polarization of macrophages by suppressing phosphorylation of the NFκB pathway via 5-AVA, thereby attenuating the inflammatory response and protecting against liver injury.