Paeoniae Radix alba polysaccharide modulates gut microbiota to restore metabolites and promote the enteric nervous system development in colitis mice

Paeoniae Radix alba polysaccharide (PRP-AP), a pectic polysaccharide, has shown potential for treating intestinal damage in vitro. However, the role and mechanism of PRP-AP in vivo remained unclear. The 6-week-old C57BL/6 male mice and Dextran sulfate sodium salt (DSS) were selected to construct a colitis mouse model. Using DSS-induced colitis mice, we observed that 7-days’ PRP-AP administration (i.g, 50, 100, 200 mg/kg) significantly (p < 0.001) alleviated colitis in a dose-dependent manner. This was achieved by restoring gut microbiota balance, particularly involving Akkermansia muciniphila, and modulating both microbial and peripheral metabolites. PRP-AP also improved colonic barrier function by increasing the expression of Zonula occludens-1 (p = 0.004) and the number of goblet cells (p < 0.001). In addition, PRP-AP promoted the Enteric Nervous System (ENS) function by regulating dopamine metabolism in enteric glial cells and enhancing acetylcholine and vasoactive intestinal peptide biosynthesis in neurons. Further analysis suggested a link between gut microbiota, fatty acid biosynthesis, and gene expression, particularly the upregulation of Phox2a by microbial activity. Collectively, our findings demonstrate the potential of PRP-AP to serve as a novel strategy for colitis by targeting the gut microbiota-metabolite-ENS axis, revealing that PRP-AP is a promising prebiotic agent for the maintenance of gut health.