Polysaccharides derived from Rosa rugosa cv. Plena ameliorate colorectal cancer by regulating intestinal microbiota composition and lipid metabolism pathway

Abstract The aim of this study was to determine the composition of Rosa rugosa cv. Plena polysaccharide (RPP1) and investigate the mechanism involved in alleviating azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colorectal cancer (CRC). RPP2-0, RPP2-1, and RPP2-3 were purified from Rosa rugosa cv. Plena using water extraction, alcohol precipitation, and DEAE-cellulose 52 column chromatography. HPLC analysis revealed that RPP1 consisted of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, xylose, and arabinose in a molar ratio of 0.4634:0.2668:0.1025:9.4314:1.1887:0.5524:0.1941:0.5339. In an AOM/DSS-induced CRC mouse model, RPP1 significantly reduced the number of colonic polyps and ameliorated colonic shortening in both high-dose (PH) and low-dose (PL) groups. Serum ELISA demonstrated that RPP1 significantly decreased the levels of inflammatory cytokines IL-1β and TNF-α, restoring them to control levels. Based on these findings, group PL, which exhibited significant effects, was selected for multi-omics analysis to systematically elucidate the mechanism of action of RPP1. Microbiome analysis showed that RPP1 significantly reduced the abundance of Bacteroides and Desulfovibrio while increasing the relative abundance of the beneficial bacteria Eubacterium and Muribaculum. Lipidomic data indicated that RPP1 significantly downregulated phosphatidylcholine(PC) and lysophosphatidylcholine levels(LPC) in mouse feces, affecting ether lipid metabolism, glycerophospholipid metabolism, and sphingolipid metabolism pathways. Furthermore, integrated microbiome and lipidomic analysis revealed that RPP1 downregulated the levels of the key lipid LPC by modulating the abundance of Muribaculum and Clostridium. Transcriptomic results confirmed that RPP1 intervention significantly downregulated lipid metabolism-related pathways and upregulated the immune-related NOD-like receptor (NLR) and proliferator-activated receptor (PPAR) signaling pathways, thereby alleviating CRC symptoms effectively. In conclusion, RPP1 significantly improved the pathological features of CRC by modulating gut microbiota composition, regulating lipid metabolism pathways, and activating immune-related signaling pathways.