Background and Purpose The purpose of our research was to investigate the therapeutic effect of Panax notoginseng polysaccharides (PNP) in ameliorating colitis and revealing its protective mechanism of the gut vascular barrier. Experimental Approach PNP was extracted using a process of pure water extraction and then precipitated by ethanol. Next, the structural properties of PNP were analyzed, including the purity of the polysaccharides, monosaccharide composition, and molecular weight. Utilizing the DSS to induce acute colitis model, ELISA assessed the levels of inflammation-related factors in serum. The types and functional expressions of immune cells were examined using flow cytometry. Additionally, immunofluorescence was applied to evaluate the integrity of the multiple gut barrier. The gut microbiota was assessed, and its mechanism of action was investigated through 16S rRNA sequencing and FISH techniques. Transplanting PNP feces into DSS-induced mice to determine the contribution of intestinal flora to PNP efficacy. Key Results Pharmacological experiments indicate that PNP can ameliorate intestinal inflammatory reactions, reduce bacterial tissue invasion, as well as maintain the integrity of the multiple gut barrier, including epithelial barrier, mucus barrier, and vascular barrier. PNP-FMT obtained similar efficacy results. Mechanically, PNP treatment modulated the gut microbiota and increased ILC3-secreted IL-22 to repair the gut vascular barrier. Conclusions and Implications The findings indicate that PNP effectively repairs intestinal epithelial and vascular barrier damage by enhancing the function of ILC3 through microbial mediation.

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.