A triple-helix white tea polysaccharide alleviates ulcerative colitis via the gut microbiota-metabolites-inflammation regulatory axis.

Ulcerative colitis (UC), a chronic inflammatory bowel disease, remains incurable with limited therapies. White tea, a traditional Chinese beverage, is known for anti-inflammatory effects, yet its active components in UC are poorly defined. Here, we identified a homogeneous pectic polysaccharide (WTP-2, 150.79 kDa) as the key anti-colitic constituent. WTP-2 contains homogalacturonan domains with →4)-α-D-GalpA-(1 → backbones, 42.47 % methyl esterification, and 14.8 % acetylation of GalpA residues. Conformation analyses revealed a triple-helix structure underlying its activity. In vitro, WTP-2 (400 μg/mL) suppressed LPS-induced TNF-α and IL-6 secretion in RAW264.7 macrophages by 57.6 % and 72.4 %, respectively, whereas helix-disrupted derivatives were ineffective. In vivo, WTP-2 (160 mg/kg) alleviated dextran sulfate sodium-induced colitis, reducing disease activity index scores by 54.5 %, preserving barrier integrity, and modulating gut microbiota and metabolites. Transcriptomic and protein analyses revealed downregulation of immune genes and inhibition of the IL-17-JNK-AP-1 pathway, with marked decreases in p-JNK, p-c-Jun, and COX-2 expression. Collectively, these results demonstrate that a triple-helix white tea polysaccharide protects against UC via a microbiota-metabolites-inflammation regulatory axis, with its in vitro anti-inflammatory activity dependent on the triple-helix structure. This study provides new insights into white tea polysaccharide structure-function relationships and highlights its therapeutic potential in UC management.