Poria cocos polysaccharides as a carbon source promotes the proliferation of Parabacteroides distasonis to ameliorate ulcerative colitis: A mechanistic study based on the secondary bile acid-TGR5 axis.

Clinical and experimental evidence suggests a link between gut microbiota dysbiosis and ulcerative colitis (UC). Although our prior work indicated that Poria cocos polysaccharides (PCP) enhance intestinal health by modulating the gut microbiota, the mechanisms underlying their protection against UC were not fully delineated. In this study, in vivo and in vitro experiments demonstrated that PCP supplementation ameliorates dextran sulfate sodium (DSS)-induced gut microbiota dysbiosis, increasing the abundance of Parabacteroides distasonis (P. distasonis). The protective role of P. distasonis was confirmed by its supplementation in microbiota-depleted mice, which restored gut barrier integrity and mitigated histopathological damage. Metabolomics analysis revealed that PCP significantly increases the levels of secondary bile acids. Further research has found that PCP serves as a carbon source to promote the proliferation of P. distasonis, enhances bile salt hydrolase activity, stimulates the production of (Deoxycholic acid, DCA), (Lithocholic acid, LCA), and (Isolithocholic acid, isoLCA), and alleviates UC by activating the TGR5-cAMP-PKA-NLRP3 signaling pathway. Treatment with TGR5 agonists and inhibitors in UC mice demonstrated the involvement of PCP in this pathway. Collectively, these findings indicate that PCP can be utilized as a novel prebiotic for the treatment of UC.