Structural elucidation and gut barrier-protective effects of a glucomannan polysaccharide fraction from Lanzhou lily...

Food-derived dietary polysaccharides have attracted increasing attention as functional ingredients for ulcerative colitis (UC) management. In this study, a homogeneous polysaccharide, designated LDP, was isolated from the bulbs of Lilium davidii var. willmottiae (Lanzhou lily). Structural analyses showed that LDP had a weight-average molecular weight (M_W) of 5.082 × 10³ g/mol and was mainly composed of alternating →4)-α-D-Manp-(1 → and →4)-β-D-Glcp-(1 → residues with minor branching. Conformational analysis and molecular dynamics (MD) simulations indicated that LDP adopted an extended semi-flexible coil conformation in aqueous solution. In dextran sulfate sodium (DSS)-induced colitis mice, LDP markedly alleviated disease symptoms, as evidenced by improved survival, reduced body weight loss, a lower disease activity index and attenuated histopathological injury. Mechanistically, LDP enhanced intestinal barrier integrity, significantly increased acetic acid levels and partially restored short-chain fatty acid (SCFA)-associated beneficial taxa, including Lactobacillaceae, Bifidobacterium, Allobaculum and members of Erysipelotrichaceae/Erysipelotrichia. Integrated metagenomic, proteomic, Western blot and immunological analyses further indicated that LDP attenuated intestinal inflammation by suppressing the TAB1/MAP2K4-centered MAPK signaling pathway, as evidenced by reduced TAB1 and MAP2K4 expression and decreased p38 phosphorylation, and by restoring the Th17/Treg balance in mesenteric lymph nodes (MLNs). These findings suggested that LDP alleviated DSS-induced colitis through coordinated regulation of gut microbiota, microbial metabolism, MAPK inflammatory signaling and mucosal immunity.