Medjool Date Seed Polysaccharides Attenuate DSS‐Induced Colitis and Associated Hepatic Oxidative Injury in Mice, Accompanied by Gut Microbiota Alterations

ABSTRACT Inflammatory bowel disease (IBD) is a chronic intestinal disorder that is often accompanied by oxidative stress, immune imbalance, disruption of the intestinal barrier, and liver complications linked through the gut‐liver axis. In this study, we explored the protective effects of Medjool date seed polysaccharides (MDSP) in a dextran sulfate sodium (DSS)‐induced colitis mouse model. Structural characterization using transmission electron microscopy (TEM), Fourier‐transform infrared (FTIR), x‐ray photoelectron spectroscopy (XPS), high‐performance liquid chromatography (HPLC), and nuclear magnetic resonance (NMR) analyses showed that MDSP consisted of oxygen‐rich heteropolysaccharide structures with notable antioxidant potential. Oral administration of MDSP (150 and 300 mg/kg) markedly alleviated DSS‐induced colitis by reducing body weight loss, disease activity, and colon shortening, while improving intestinal histological architecture and restoring MUC2 expression. MDSP also reduced the levels of pro‐inflammatory cytokines, including IL‐1β, IL‐6, IL‐17, and IL‐23, and enhanced the expression of anti‐inflammatory cytokines, such as IL‐10 and IL‐4. In addition, MDSP improved antioxidant status by increasing superoxide dismutase (SOD) and glutathione (GSH) levels and lowering myeloperoxidase (MPO), malondialdehyde (MDA), nitric oxide (NO), ALT, and AST levels, indicating significant protection against oxidative stress and colitis‐associated liver injury. Analysis of the gut microbiota further demonstrated that MDSP helped restore microbial balance by suppressing harmful bacteria, including Klebsiella and Desulfovibrio , while promoting beneficial genera such as Lactobacillus and Bifidobacterium . The aforementioned findings suggest that MDSP can effectively reduce intestinal inflammation, improve antioxidant defenses, protect liver function, and regulate gut microbiota composition, highlighting its application prospects as a preventive control for IBD.