Garlic Polysaccharides Ameliorate AOM/DSS-Induced Colon Tumorigenesis: A Multi-Omics Mechanistic Study

As important sources of prebiotics, natural plant polysaccharides have been widely investigated owing to their excellent anti-inflammatory, anti-tumor, immunomodulatory, and gut microbiota-regulating effects. This study explored the anti-tumor effects and underlying mechanisms of garlic polysaccharides (GP-1) in a mouse model of azoxymethane/dextran sulfate sodium-induced colitis-associated colon tumorigenesis. GP-1, identified as a typical fructan (molecular weight: 3583 Da) with (2→1) and (2→6) linkages, significantly improved survival rate, reduced colon tumor burden, and alleviated intestinal bleeding in tumor mice. Furthermore, intestinal damage was significantly attenuated, as evidenced by enhanced barrier integrity, downregulated pro-inflammatory cytokines, and elevated antioxidant enzyme activities. GP-1 also inhibited aberrant epithelial proliferation by suppressing Ki67 protein expression. Multi-omics analyses revealed that these benefits might be associated with gut microbiota and metabolite remodeling, as well as transcriptional suppression of key inflammatory/tumorigenic pathways. Our findings highlighted the inhibitory effect of GP-1 on colon tumorigenesis and supported its potential as a gut-health-promoting functional food ingredient.