Stevia rebaudiana arabinogalactan alleviates dextran sulfate sodium-induced colitis: associations with gut microbiota and PI3K-Akt/NF-κB signaling

A homogeneous arabinogalactan, UA-SRP1, was isolated from Stevia rebaudiana . • UA-SRP1 alleviated DSS-induced colitis and restored gut barrier integrity in mice. • UA-SRP1 supported epithelial regeneration, reduced inflammation and oxidative stress. • UA-SRP1 alleviates colitis via microbiota-dependent and independent mechanisms. Stevia rebaudiana polysaccharides have great potential to intervene in ulcerative colitis (UC) as functional food ingredients for gut health. This study isolated and structurally characterized a homogeneous arabinogalactan (UA-SRP1, 1.44 × 10 6  Da), mainly composed of galactose and arabinose. It possesses a (1 → 6)-β-D-Gal p backbone with heterogeneous side-chain substitutions occurring at the O-3 positions of the galactopyranosyl residues. In a DSS-induced UC mice model, UA-SRP1 treatment effectively alleviated clinical symptoms and histopathological damage, strengthened the intestinal barrier by upregulating ZO-1 and MUC-2, and attenuated inflammation and oxidative stress. It was also associated with remodeling of the gut microbiota (e.g., enrichment of Lactobacillus and Akkermansia ) and restoration of beneficial metabolites, such as short-chain fatty acids. Transcriptomic and Western blot analyses showed treatment-associated changes in PI3K-Akt and NF-κB signaling. Antibiotic depletion further indicated that microbiota status influenced part of the UA-SRP1-associated response. Collectively, these findings demonstrate the protective effects of UA-SRP1 against DSS-induced colitis and reveal coordinated changes in gut microbiota, microbial metabolites, and host signaling, supporting its further investigation as a potential functional food ingredient for gut health. Download: Download high-res image (287KB) Download: Download full-size image