Low molecular weight water-soluble Gastrodia elata polysaccharide GEP-2 alleviates DSS-induced ulcerative colitis by enhancing the intestinal barrier, modulating gut microbiota, and suppressing inflammation.

Gastrodia elata Blume, a traditional Chinese herb, exhibits biological activities linked to its polysaccharides. This study isolated a low-molecular-weight, water-soluble polysaccharide, GEP-2, from Gastrodia elata and investigated its protective effect on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice, focusing on intestinal barrier function, immune response and microbiota regulation. UC was induced in mice via oral administration of 3% DSS for 7 days. Assessments included disease activity index (DAI), colon length, serum cytokines, tight junction proteins (ZO-1, occludin, claudin-1), NF-κB/STAT3 expression, and gut microbiota analysis via 16S rRNA sequencing. It was found that GEP-2, a branched polysaccharide with α-d-glucose as the main chain with substitutions such as GalA, Gal, Rha, and Ara, exhibited broad molecular weight distribution (Mn = 2.54 kDa, Mw = 9.24 kDa). Compared to the DSS model group, GEP-2 significantly reduced DAI scores, weight loss, colon shortening, and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), while elevating anti-inflammatory IL-10. It enhanced intestinal barrier function by upregulating tight junction proteins and suppressing the NF-κB p65/STAT3 signaling pathway. Results also showed that GEP-2 affects gut microbiota composition, enriching beneficial taxa like Dubosiella, Clostridia UCG-014, and Alistipes. These findings highlight that GEP-2 has potential as a protective agent for UC via microbiota-gut axis regulation.