Gut microbiota-mediated immunomodulation underlies the anti-tumor effects of a novel ginseng polysaccharide

A novel ginseng polysaccharide (GP-A) was investigated for its immune modulation and anti-tumor effects in an S180 sarcoma mouse model. GP-A, with a molecular weight of 1.121 × 10 4  g/mol, primarily consists of a polysaccharide main chain formed by →4)-α-D-Glc p -(1 → sugar residues, along with 1,3,5-Ara f and 1,5-Ara f side chains. In vivo, GP-A improved immune organ recovery and serum cytokine levels, restoring immune balance by downregulating IL-10 and upregulating TNF-α and IL-6. GP-A enhanced IL-6-mediated PI3K/AKT signaling, promoting splenic immune cell proliferation and activation, thereby improving the host's anti-tumor immune response and inhibiting tumor cell proliferation. Oral administration of GP-A (100, 200, 400 mg/kg) for 10 days significantly reduced tumor size, volume, and weight, with the 400 mg/kg group achieving a 66.52 % tumor inhibition rate (96.91 % in the CTX group). Additionally, GP-A improved gut microbiota dysbiosis induced by the tumor, increasing Lactobacillus abundance while decreasing Alloprevotella and Bacteroides . It also elevated short-chain fatty acid (SCFA) levels, particularly propionate and butyrate, maintaining gut microecological balance. GP-A exhibited milder and safer immune modulation, suggesting its potential as a novel immune modulator for cancer therapy.