<i>Lactiplantibacillus plantarum</i> 104 cell-free supernatant improved bile acid metabolism by regulating gut microbiota of high-fat diet mice

<em>Lactiplantibacillus</em> <em>plantarum </em>104, which was previously screened in the laboratory, has been confirmed to have the effect of lowering lipids and regulating intestinal microbial homeostasis. However, the mechanism of action of its fermentation supernatant in alleviating metabolic disorders is unclear.<strong> </strong><em>L. plantarum </em>104 cell-free<em> </em>supernatant (LP104s) was fed to high-fat C57BL/6N mice for 8 weeks. The intervention of LP104s increased the concentration of conjugated bile acids in the ileum, especially taur-α/β-muricholic acid sodium salt (T-α-MCA or T-β-MCA), inhibited intestinal farnesoid X receptor (FXR)-related signaling pathways. LP104s reduced cholesterol levels by increasing the synthesis of hepatic cholic acid (CA), chenodeoxycholic acid (CDCA), and the excretion of bile acids in feces. Moreover, western blotting results showed that TLR2/NF-ҡB signaling pathway expression was inhibited. In addition, 16S rDNA sequencing results showed that LP104s regulated the relative abundance of bacteria associated with inflammatory response and obesity (<em>Prevotella, Ruminococcus, </em>and<em> Clostridium</em>). Therefore, this paper further elaborates the role of gut microbiology and bile acids in improving metabolism from the perspective of secondary bile acids and intestinal chronic inflammation and also lays a theoretical foundation for the next step in the development of fermentation products of this strain.