Asparagus polysaccharide attenuates atherosclerosis by modulating gut microbiota and metabolites

Atherosclerosis remains a critical driver of cardiovascular morbidity; however, therapeutic strategies for halting its progression remain suboptimal. To date, there are no reports of asparagus polysaccharide (AP)-the active component of Asparagus cochinchinensis (Lour.) Merr.-promoting human health by modulating the gut microbiota. In the present study, we provided a high-fat diet (HFD) to an ApoE^-/- murine model to investigate the mechanisms by which AP mitigates atherosclerotic pathogenesis. Our results demonstrated that AP significantly alleviated HFD-induced aortic lesions, decreased serum lipid levels (p < 0.01), and markedly decreased the mRNA levels of inflammatory factors in the aorta (p < 0.001). Using 16S rRNA sequencing, we observed that AP reversed HFD-induced alterations in the relative abundances of Bacteroidetes and Firmicutes at the phylum level, and remarkably increased the abundance of Actinobacteria (p < 0.01). Using untargeted metabolomics analysis, we identified 10 key metabolites associated with atherosclerosis. Furthermore, while L-glutaminyl-L-tryptophan levels increased in the faeces and decreased in the blood following HFD induction, AP treatment reversed this trend. This study provides the first evidence that AP exerts its anti-atherosclerotic effects through the gut microbiota-metabolite axis, with L-glutaminyl-L-tryptophan emerging as a potential, novel translational biomarker for therapeutic monitoring.