Ginseng Polysaccharides Ameliorate Colorectal Tumorigenesis through Lachnospiraceae-Mediated Regulation of CD8+T Cells and MDSCs Immunity

Background: and Purpose: Probiotics and their metabolites play a critical role in immunotherapy for colorectal cancer (CRC) and intestinal damage. This study aims to investigate the therapeutic potential of ginseng polysaccharides (GPS) in inhibiting colorectal tumorigenesis, find the key probiotics, and uncover the underlying mechanisms. Experimental Approach: We investigated the effects of GPS on tumorigenesis in AOM/DSS-induced and MC38-induced CRC models. GPS-related probiotic Lachnospiraceae bacterium (L.B.) was determined by 16S rRNA sequencing and its functions of antitumor and immunoregulation were further in substantiated two CRC models. Key Results: GPS significantly ameliorates colorectal tumorigenesis and microbial dysregulation. Mechanistically, GPS supplementation promoted the proliferation of beneficial Lachnospiraceae bacterium (L.B.), leading to increased short-chain fatty acids (SCFAs) production. The effective anti-CRC effects of key probiotics were further substantiated by their ability to inhibit myeloid-derived suppressor cells (MDSCs) and enhance the infiltration and activation of CD8+ T cells. Conclusion and Implications: These findings highlight the pivotal role of GPS-induced alterations in the potential probiotics L.B. production in CRC suppression, emphasizing the potential of GPS in immune regulation for microbiome-targeted cancer therapies.