<i>Docynia delavayi</i> (Franch.) Schneid polyphenols alleviate dextran sulfate sodium-induced colitis by regulating the gut microbiota

<i>Docynia delavayi</i> (Franch.) Schneid is rich in polyphenols; however, its functions remain unclear. In this study, we identified and characterized the key constituents of <i>D. delavayi</i> fruit polyphenols (DDP), validated their anti-inflammatory effects, and provided insights into their underlying mechanisms of action. UPLC-MS/MS was used to quantify the major phenolic compounds in DDP, including glycitin, procyanidin B2, vitexin, myricitrin, astilbin, chlorogenic acid, phlorizin, (-)-epicatechin, naringenin-7-<i>O</i>-glucoside, taxifolin-7-<i>O</i>-rhamnoside, rhoifolin, methylnissolin-3-<i>O</i>-glucoside, and scutellarein. In the dextran sulfate sodium-induced colitis mouse model, DDP significantly improved colon length and the disease activity index. It also reduced the expression of inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Metagenomic analysis revealed that DDP increased gut microbiota diversity, particularly enriching species capable of producing short-chain fatty acids (SCFAs), such as <i>Lawsonibacter</i> and <i>Ruminiclostridium</i>. Metabolomic data further demonstrated the upregulation of SCFA-associated pathways, such as glycolysis and pyruvate metabolism, with elevated colonic acetate, propionate, and butyrate levels corroborating these findings. Multi-omics analysis linked SCFAs to reduced inflammation. Collectively, these findings suggest that SCFAs play a pivotal role in the anti-inflammatory effects of DDP by modulating the gut microbiota to enhance SCFA biosynthesis. These findings demonstrate that SCFAs serve as critical mediators of the anti-inflammatory properties of DDP, highlighting their considerable potential as natural therapeutic agents for intestinal inflammation.