Front Microbiol. 2026 Jun 18;17:1768989. doi: 10.3389/fmicb.2026.1768989. eCollection 2026.
ABSTRACT
BACKGROUND: While fucoidans show anti-atherosclerotic potential, their impact on this gut-host axis is unclear. This study investigated the effects of Fucus vesiculosus fucoidan, alone and combined with simvastatin, on gut microbiota and metabolome in an atherosclerotic rabbit model that closely recapitulates key features of human atherosclerotic pathogenesis.
METHODS: Atherosclerosis was induced in New Zealand rabbits via high-fat diet feeding combined with balloon catheter injury. Animals in the experimental groups (n = 6 per group) were treated with either F. vesiculosus fucoidan alone (100 mg/kg) or a combination of fucoidan (100 mg/kg) and simvastatin (5 mg/kg). Lipid profiles were assayed using commercial kits, and aortic pathological changes were evaluated by Oil Red O staining. Genomic DNA from intestinal contents was analyzed by polymerase chain reaction, and untargeted metabolomics were performed using liquid chromatography-tandem mass spectrometry.
RESULTS: Treatments significantly reduced atherosclerotic plaque formation. This effect was particularly pronounced when fucoidan was combined with simvastatin, reducing plaque formation from 41.77 ± 16.02% to 5.91 ± 8.03% in the abdominal aorta and from 10.72 ± 3.49% to 2.29 ± 2.30% in the thoracic aorta (Model vs. combination group). The treatment also ameliorated hyperlipidemia, as shown by decreased plasma TC (24.55 ± 0.73 to 17.45 ± 0.58 mmol/L) and TG (7.75 ± 0.46 to 0.83 ± 0.25 mmol/L) in the combination group compared to the Model group. Both intervention groups exhibited enhanced microbial diversity and increased species richness across all taxonomic levels compared to the model group. Moreover, fucoidan and combination treatments significantly upregulated 83 and 128 metabolites and downregulated 125 and 121 metabolites, respectively. KEGG enrichment analysis indicated that these metabolic changes were associated with multiple pathways. Moreover, the combination therapy may mitigate certain side effects associated with simvastatin, although this possibility requires further investigation.
CONCLUSION: The combination of F. vesiculosus fucoidan and simvastatin holds promising therapeutic potential for preventing and treating atherosclerosis. Our findings provide novel evidence that this enhanced effect is likely linked to structural and functional modifications in the gut microbiota and its associated metabolic profile, supporting a multifaceted strategy that extends beyond lipid-lowering.
PMID:42395903 | PMC:PMC13323129 | DOI:10.3389/fmicb.2026.1768989