Sea Buckthorn Polysaccharides Regulate Bile Acids Synthesis and Metabolism through FXR to Improve Th17/Treg Immune Imbalance Caused by High-Fat Diet

The equilibrium between Th17 and Treg cells plays a crucial role in the imbalance of intestinal immune homeostasis caused by a high-fat diet (HFD). SPa denotes the main component of sea buckthorn polysaccharides; its effects and potential pathways on inflammation caused by HFD-induced Th17/Treg immune imbalance are still unclear. Therefore, we conducted research on it. We discovered that SPa mitigates HFD-induced intestinal inflammation and barrier dysfunction by modulating specific pathways. Moreover, we observed that SPa significantly enriches KEGG pathways related to secondary bile acid biosynthesis and steroid degradation, especially enriching bacterial strains holding bile salt hydrolase (BSH) and 3β-hydroxysteroid dehydrogenase, such as Muribaculaceae_bacterium, Phocaeicola_vulgatus, and Roseburia_zhanii . Notably, SPa ameliorated the HFD-induced Th17/Treg imbalance through dual mechanisms: first, the secondary bile acids (isoLCA, DCA, and LCA) produced by gut microbiota metabolism activated FXR and VDR receptors. Second, SPa inhibited the reduction of Treg cells by suppressing the TLR4-TRPV1-CGRPα-AMRP1 signaling pathway. Moreover, SPa alleviated HFD-induced liver inflammation, which was consistent with SPa regulating bile acid synthesis and transport in the liver through the FXR-FGF15-FGFR4 and OSTα/OSTβ-FXR-SHP pathways. Collectively, our findings suggest that SPa can restore HFD-induced immune homeostasis imbalance and liver inflammation via the microbiota-gut-liver axis.