Therapeutic mechanisms of polysaccharides as mediators of the gut-heart axis in cardiovascular diseases

Cardiovascular disease (CVD) remains a leading cause of global health burden, with conventional therapeutic strategies often constrained by inherent limitations. The emerging concept of the gut-heart axis, highlighting the intricate crosstalk between the gut microbiota and the cardiovascular system, has opened novel avenues for CVD prevention and treatment. This review comprehensively elucidates the therapeutic mechanisms and translational potential of polysaccharides as pivotal mediators of the gut-heart axis in the context of CVD management. Characterized by distinct physicochemical properties, polysaccharides exhibit significant capacity to reshape gut microbial communities and metabolic profiles, enhancing the production of beneficial metabolites like short-chain fatty acids (SCFAs), while suppressing pathogenic compounds such as trimethylamine N-oxide (TMAO). These effects underlie their pleiotropic cardioprotective effects, including antioxidant capacity, immune modulation, endothelial function improvement, and lipid metabolism regulation. Moreover, polysaccharides reinforce intestinal barrier integrity, remodel microbiota-host metabolic networks, and activate critical signaling pathways such as <em>Nrf2</em> and TLR4/NF-κB, thereby attenuating atherosclerosis, hypertension, and myocardial injury. Clinical evidence further supports that polysaccharide-probiotic synbiotic interventions synergistically improve lipid profiles and vascular function. Despite promising prospects, the structure-activity relationships and personalized application of polysaccharides require further investigation. Their biocompatibility, multi-target mechanisms, and drug delivery potential make polysaccharide compelling candidates for innovative CVD therapeutics. Future research should leverage multi-omics technologies to decipher the complex interplay among polysaccharide, gut microbiota, and host, ultimately advancing precision nutrition and microbiome-targeted therapies.