With global aging, intestinal homeostasis disruption contributes to inflammation, oxidative stress, and metabolic disorders. This study assessed fucoidan at doses of 100, 250 and 500 mg/kg in aged mice. The high dose (500 mg/kg) improved food intake, body weight and intestinal transit, and elevated α-amylase activity. It also relieved oxidative stress, strengthened intestinal tight junctions and restored mucosal morphology. Multi-omics analyses revealed that fucoidan reshaped the gut microbiome—enriching beneficial taxa (e.g., Akkermansia) while suppressing opportunistic pathogens—and increased short-chain fatty acid production. Untargeted metabolomics indicated enrichment of antioxidant and barrier-protective metabolites and clearance of cytotoxic compounds, with key impacts on amino acid, lipid, and energy metabolism. Overall, fucoidan systematically restores aging intestinal homeostasis via a “microbiota–metabolite–host” axis, supporting its potential as an anti-aging functional food.
