Enzymatically Hydrolyzed Wheat Bran-Derived Zinc Phytate Ameliorates Ulcerative Colitis via Synergistic Regulation of the Gut Microbiota-Intestinal Barrier Axis

This study evaluates the therapeutic potential of enzymatically hydrolyzed wheat bran-derived zinc phytate (EEPZ) in a dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model, with chemically synthesized zinc phytate (ZnPA) and whole wheat bran (WHB) as controls. EEPZ modulated gut microbiota by increasing <i>Lactobacillus vaginalis</i> (0.15% to 18.6%) and reducing <i>Desulfovibrio</i> (5.19% to 1.29%). Metabolically, <i>Lactobacillus vaginalis</i> converted EEPZ or standard zinc phytate into bioavailable inositol phosphates (e.g., IP3, IP4, IP5) and ionic zinc in vitro and in vivo. Concomitantly, EEPZ altered short-chain fatty acid and bile acid profiles (Chenodeoxycholic acid increased by 30% and lithocholic acid increased by 80%). Mechanistically, EEPZ strengthened intestinal barrier integrity via HDAC3 and tight junction proteins (ZO-1, occludin) upregulation, while concurrently suppressing the PI3K/AKT/NF-κB signaling pathway. Collectively, EEPZ emerges as a novel, natural UC therapeutic candidate.