Wine processing induced structural modification of Polygonati Rhizoma polysaccharide and their enhancement of Tc1 cell immunomodulatory activity via microbiota-mediated butyrate metabolism

The herb Polygonati Rhizoma is highly esteemed for its immune regulatory therapeutic and nutritive properties, with polysaccharide identified as the principal components that play a pivotal role in immune response modifying. In China, the immunomodulatory effects of Polygonati Rhizoma polysaccharide (PRP) are believed to enhanced after wine processing. However, the structural changes and underlying mechanisms remain insufficiently elucidated. We isolated and purified PRP and wine processing PRP (WPRP) for structural and functional analysis. Structural analysis showed a processing-driven shift from a low-molecular-weight fructo-glucosyl fructan in PRP (1.85 kDa) to a higher-molecular-weight, pectin-type polysaccharide in WPRP (7.31 kDa) enriched in arabinose, galactose and galacturonic acid. The precise structural transition was from α-D-Glcp → [2)-β-D-Fruf-(1]₃ → 2)-β-D-Fruf-(1 → 6)-α-D-Glcp-(1 → 2)-β-D-Fruf → in PRP to → 4)-β-D-Galp-(1 → 4)-β-D-Galp-(1 → 4)-α-D-GalAp-(1 → 5)-α-L-Araf-(1 → [5)-α-L-Araf-(1]₃ → 4)-α-D-GalAp-(1 → 4)-α-D-GalAp-(1 → in WPRP. WPRP exhibited stronger immunomodulatory activity than PRP in immunosuppressed mice. Mechanistically, galacturonic acid-rich pectins and arabinan driven by wine processing are preferential fermentable substrates for butyrate-producing gut bacteria, which promoted Tc1 cell activation/differentiation, and preserved intestinal epithelial integrity. These findings reveal that PRP drives structural remodeling after wine processing, modulating microbial butyrate metabolism and promoting Tc1 activation, which provide novel insights into the modern medical value of traditional dietary resources.