16S rRNA gene amplicon sequencing of 45 C57BL/6J mice
In this study, we aim to investigate the molecular mechanisms by which L. paracasei JBC1 protects against HFHCD induced MASLD. Hepatic proteomic analysis identified the PPAR pathway as a central node, which was subsequently validated using GW6471 (a PPARa angtagonist that promotes SMRT corepressor binding) and GW9662 (a selective irreversiblea PPARg antagonist ). JBC1 attenuates hepatic steatosis primarily through PPARa activation coupled with PPARg suppression. Integrated metabolomic and microbiota analyses further revealed that hepatic PPARa activation reshapes tahe intestinal bile acid profile and promotes the enrichment of benefigcial commensals, including Akkermansia muciniphila.