Undaria pinnatifida Polysaccharide Ameliorates DSS-Induced Murine Colitis by Regulating Intestinal Inflammation, Gut Microbiota and Metabolism

Ulcerative colitis (UC) is a chronic intestinal disorder characterized by intestinal inflammation, microbiota dysbiosis, and metabolic disturbances. This study aimed to explore the ameliorative effect and related mechanisms of <i>Undaria pinnatifida</i> polysaccharide (UPP) on dextran sulfate sodium (DSS)-induced murine colitis. Mice were administered low (50 mg/kg) and high (200 mg/kg) concentrations of UPP by gavage, followed by induction of colitis using 2.5% DSS in the drinking water, while mice gavaged with distilled water served as the model group (DSS group). Mice in the blank group were gavaged with sterile water and had no DSS added to their drinking water. The results showed that UPP ameliorated DSS-induced colitis in a concentration-dependent manner, with the high-dose group (200 mg/kg) exerting a more significant effect. Specifically, UPP effectively alleviated weight loss, reduced the disease activity index (DAI) score, restored colon length, mitigated pathological damage to colonic tissue, and enhanced intestinal mucus secretion. At the mechanistic level, compared with the model group, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the colonic tissue of mice in the high-dose UPP group were significantly reduced by 47.60%, 22.59%, and 17.54%, respectively (all <i>p</i> < 0.05). 16S rRNA sequencing results indicated that the UPP-H group significantly increased the abundance of beneficial genera including <i>Akkermansia</i>, <i>Parabacteroides</i> and <i>Turicibacter</i>, while reducing the proportion of potential pathogenic genera such as <i>Escherichia</i> and <i>Clostridium</i>. Metabolomics analysis revealed that the high-dose UPP group reversed the disorder of 32 differential metabolites in the model group and restored the homeostasis of core metabolic pathways such as amino acid metabolism and fatty acid metabolism. Correlation analysis suggested that UPP may exert anti-inflammatory effects by regulating intestinal microbiota structure and further affecting metabolic networks. In conclusion, UPP can alleviate DSS-induced murine colitis through three pathways: inhibiting intestinal inflammatory response, restoring intestinal microbiota balance, and correcting metabolic disturbances, providing experimental evidence for its potential as a candidate substance for UC intervention.