IDDF2024-ABS-0035 Angelica dahurica polysaccharides ameliorate colitis by reducing the restriction of gut microbiota-derived imidazole propionate on PPAR-γ signaling activation

<h3>Background</h3> <i>Angelica dahurica radix</i> (ADR), the root of the botanical family Apiaceae, has been used to treat colitis. Plant-derived polysaccharides exhibit potential immunomodulatory effects. The objective of this research was to investigate the effectiveness of ADR-derived polysaccharides (RP) in treating colitis. <h3>Methods</h3> The features of RP were analyzed. The colitis mice were given RP and body weight was recorded once a day. Colon length, the level of inflammatory cytokines, and the function of the intestinal barrier were analyzed. Intestinal flora structure and metabolic profiles were detected. FMT and PGF mice were employed to estimate the action of gut flora in the therapeutic effect of RP. A microbial metabolite, imidazole propionate, was given to mice for detecting the underlying molecular mechanisms. <h3>Results</h3> Analysis of the structure revealed that RP consisted of (→4)-α-D-Glcp-(1→ and →4)-α-D-Galp-(1→). RP could alleviate DSS-induced colitis. FMT and antibiotic treatment confirmed the microbiota-dependent regulatory effect of RP, especially downregulating the concentration of imidazole propionate (ImP). Using RNA-sequencing analysis, it is shown that ImP may be an inhibitor of the peroxisome proliferator-activated receptor gamma (PPAR-γ). <h3>Conclusions</h3> Our findings suggest that RP may protect against colitis by activating the PPAR-γ signaling pathway by reducing the restriction of gut microbiota-derived IMP.