A gut microbiota–stem cell axis mediates the anti‐intestinal aging effect of fucoidan from Apostichopus japonicus

BACKGROUND: Apostichopus japonicus is a traditional medicinal and culinary species, with existing anti-aging research primarily focusing on its bioactive peptides. In contrast, the anti-aging potential of its major polysaccharide, fucoidan (Aj-FUC), remains largely unexplored. Since the intestine is a central target in the aging process and the primary site for polysaccharide interaction, this study investigates the protective effects and underlying mechanisms of Aj-FUC against d-galactose (d-Gal)-induced intestinal senescence in mice. RESULTS: Aj-FUC significantly improved intestinal function, including restoration of villus structure and colon length, as well as enhancement of motility, absorption, and digestive enzyme activity. Additionally, Aj-FUC ameliorated the senescence-associated secretory phenotype, reduced oxidative stress levels, and downregulated mRNA expression of P16, P21, and P53, showing strong anti-aging effects. Meanwhile, Aj-FUC increased mRNA and protein levels of tight junction proteins, indicating improved intestinal barrier function. Further research revealed that Aj-FUC activated the Wnt/β-catenin pathway and promoted the proliferation of intestinal stem cells (ISCs). Moreover, Aj-FUC remodeled the gut microbiota and enriched Lactobacillus, thereby promoting ISC growth. CONCLUSION: Aj-FUC mitigates intestinal aging primarily by modulating the gut microbiota and subsequently promoting ISC-mediated epithelial renewal via the Wnt/β-catenin pathway. These findings highlight the promise of Aj-FUC as a marine-based prebiotic functional food ingredient for improving intestinal health during aging. © 2026 Society of Chemical Industry.