Neutral polysaccharide from Dendrobium officinale alleviates acute alcohol-induced liver injury via the gut microbiota-short chain fatty acids-liver axis.

The structure and bioactivities of a new neutral polysaccharide (DOP) from Dendrobium officinale were investigated. The DOP was obtained by hot-water extraction, ethanol precipitation and further purification with DEAE cellulose-52. The DOP molecular weight of the main peak was 422.74 kDa and mainly contained glucose and mannose with molar ratios of about 1:3. In acute alcoholic liver injury (AALI) model, DOP attenuated liver injury by reducing ALT, AST and TG levels, alleviated oxidative stress by restoring SOD and CAT activities and reducing MDA content, and suppressed inflammation by inhibiting lipopolysaccharide (LPS), IL-6, IL-1β, and TNF-α levels. The gut-liver axis modulation was achieved by strengthening intestinal barrier function (ZO-1, Occludin, Claudin-1), restoring microbial balance, and promoting the production of advantageous metabolites. DOP intervention increased the relative abundance of Ligilactobacillus, Akkermansia, and Lachnospiraceae_NK4A136_group to reverse gut microbiota disorder, and improved acetic acid, butyric acid and propionic acid levels. DOP alleviated alcohol-induced liver injury by modulating gut microbiota composition, enhancing short-chain fatty acids (SCFAs) production, restoring intestinal barrier integrity, and curbing LPS leakage. This study demonstrated the potential of DOP as a functional food for AALI mitigation while establishing the foundation for therapeutic product development.