Bitter Melon Polysaccharides Enhance Goblet Cell Function and Mucosal Integrity in DSS‐Induced Colitis Through Microbiota Remodeling

ABSTRACT Bitter melon polysaccharides (BMPs), a key bioactive component of bitter melon, exhibit a range of biological activities including gut microbiota regulation, immune modulation, and antioxidant activity. Based on previous evidence of its protective effect on the colonic mucus barrier under high‐fat‐diet condition, this study evaluated the therapeutic potential of BMP in dextran sulfate sodium (DSS)‐induced ulcerative colitis (UC) in mice. BMP treatment alleviated typical UC symptoms, including body weight loss, colon shortening, and elevated disease activity index (DAI) scores, and improved histopathological damage and restored colonic barrier integrity. Furthermore, colonic barrier function was strengthened, with a thicker colonic mucus layer and increased goblet‐cell density. BMP significantly reduced colonic levels of IL‐1β (by 82.63%), TNF‐α (by 52.98%), and MDA (by 47.72%), and lowered serum lipopolysaccharide (by 40.01%). 16S rRNA sequencing showed that BMP remodeled gut microbiota, enriching beneficial genera ( Ligilactobacillus and Dubosiella ), and suppressing pathogenic taxa ( Escherichia‐Shigella ), associated with elevated short‐chain fatty acids, especially propionate and butyrate. BMP significantly upregulated the expression of the mucin MUC‐2 , the goblet‐cell factors trefoil factor 3 ( TFF3 ) and resistin‐like molecule beta ( RELM‐β ), promoting mucin synthesis and secretion. In conclusion, BMP alleviated colitis via a barrier‐centric mechanism involving microbiota modulation, SCFA production, and enhanced mucus secretion.