Gut microbiota-based bile acid metabolism mediates the intestinal barrier protection of Phellodendri chinensis Cortex polysaccharide against ulcerative colitis.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC), a form of inflammatory bowel disease (IBD), is marked by the occurrence of colonic mucosal damage and immune system dysfunction. A notable challenge in the management of UC is the paucity of long-term effective and safe medications. Phellodendri Chinensis Cortex polysaccharide (PCP), one of the main bioactive compounds in Phellodendri Chinensis Cortex, exerts anti-inflammatory and immunomodulatory effects. However, the effects and mechanisms of PCP on mice with ulcerative colitis remain unclear. AIM OF THE STUDY: This study explores that PCP attenuates colitis mice via regulation of gut microbiota and bile acid metabolism. MATERIALS AND METHODS: Monosaccharide composition, molecular weight analysis, infrared spectroscopy, scanning electronic microscopy was used to analyze the chemical characterization of PCP. Mice were administrated by 3 % DSS for establishment of ulcerative colitis model and treated with PCP for 7 days. 16S rRNA gene sequencing and fecal microbiota transplantation (FMT) experiments was performed to evaluate the effect of gut microbiota in PCP-treated colitis mice. Targeted metabolomics analysis of bile acids (BAs) and in vivo inhibition of FXR were performed to analyze the key b BAs and key mechanism of PCP in colitis mice. RESULTS: PCP alleviated colitis-associated symptoms, repaired, injured intestinal barrier and promoted FXR activation in DSS-induced colitis mice. 16S rRNA gene sequencing found that PCP increased beneficial microbiota such as Bifidobacterium and Lactobacillus, while reducing pathogenic microbiota such as Bacteroides and Romboutsia in colitis mice. FMT experiment confirmed that PCP improved colitis mice and enhanced intestinal barrier integrity through gut microbiota. Simultaneously, PCP altered BA profiles, notably reducing the ratios of primary to secondary BAs and conjugated to unconjugated BAs, with a particularly pronounced effect on the TαMCA/αMCA ratio. Finally, FXR antagonist Gly-β-MCA reversed the protect effect of PCP against colitis. CONCLUSION: Taken together, our study demonstrates that PCP alleviates DSS-induced colitis symptoms and restores intestinal barrier by gut microbiota-BA metabolism-FXR axis.