Structural characterization of an α-glucan from Dendrobium officinale and its gut microbiota-dependent protective effects against DSS-induced ulcerative colitis in mice.

A homogeneous polysaccharide, DOP-W-1, was isolated from Dendrobium officinale and identified as a low-molecular-weight branched α-glucan with a molecular weight of 9.76 kDa, mainly consisting of →4)-α-D-Glcp-(1 → and →4,6)-α-D-Glcp-(1 → residues. This study aimed to determine whether DOP-W-1 protects against dextran sulfate sodium (DSS)-induced colitis through gut microbiota-mediated mechanisms. In DSS-induced colitic mice, DOP-W-1 markedly alleviated disease severity, as shown by reduced body weight loss and disease activity index, restored colon length, improved histopathological injury, preserved mucus barrier integrity, decreased intestinal permeability, and rebalanced inflammatory cytokines. 16S rRNA sequencing revealed that DOP-W-1 selectively reshaped the gut microbiota, characterized by enrichment of Akkermansia and suppression of DSS-associated taxa, including Turicibacter and Alistipes. Importantly, antibiotic-mediated microbiota depletion largely abolished the protective effects of DOP-W-1, whereas fecal microbiota transplantation from DSS + DOP-W-1-treated donor mice reproduced the anti-colitic phenotype, demonstrating that gut microbiota is essential for its protective activity. Functional analysis further showed that DOP-W-1 restored microbial carbohydrate-active enzyme profiles associated with α-glucan utilization. Untargeted metabolomics and short-chain fatty acid analysis indicated that DOP-W-1 corrected aromatic amino acid-related metabolic disturbances, restored D-glucaro-1,4-lactone, and recovered short-chain fatty acid production. Collectively, these findings suggest that DOP-W-1 acts as a microbiota-targeted α-glucan that alleviates experimental colitis by restoring microbial carbohydrate metabolism, metabolic homeostasis, and mucosal barrier function.