The neutral and acidic polysaccharides from Ginseng are metabolized by specific gut microbial taxa and confer immunomodulatory effects

Ginseng (Panax ginseng C. A. Mey.) exerts immunomodulatory effects partly mediated by its polysaccharides and interactions with gut microbiota. However, due to the structural complexity of ginseng polysaccharides, knowledge of their oral fate and direct microbiota interactions remains limited.

This study aims to elucidate the oral fate of neutral and acidic polysaccharides in ginseng, analyze core gut microbiota genera and their immunomodulatory effects mechanisms.

Structural analysis was conducted on neutral and acidic polysaccharides from ginseng. Thereafter, in vitro digestion and fermentation were performed, with metagenomic and metatranscriptomic profiling. The results were validated in conventional and pseudo‑germ-free immunosuppressed mouse models, and the immunomodulatory mechanisms of the core gut microbiota were investigated.

The in vivo and in vitro findings indicated that neutral and acidic polysaccharides exhibit different digestive properties and gut microbiota degradation patterns, differ in short-chain fatty acid production tendencies, bind to GPR-41/43 receptors, upregulate MAPK-p38 phosphorylation, and promote proliferation of intestinal immune cells.

This work systematically elucidated the digestive characteristics of ginseng polysaccharides and laid the groundwork for future studies on the specificity and structure-function relationships of plant-derived polysaccharides.