Saccharina japonica sulfated fucans alleviate intestinal ageing‐associated epithelial deterioration and regenerative decline

BACKGROUND Intestinal ageing is characterized by progressive epithelial deterioration, barrier dysfunction and impaired regenerative capacity, which together contribute to age‐related intestinal decline. Sulfated fucans derived from Saccharina japonica (SJ‐FUC) are marine polysaccharides with potential bioactivities, although their role in intestinal ageing remains unclear. This study investigated the protective effects of SJ‐FUC in a D‐galactose‐induced ageing mouse model. RESULTS Administration of SJ‐FUC significantly alleviated intestinal ageing‐associated phenotypes by reducing oxidative stress, suppressing senescence‐associated secretory phenotype‐related inflammatory cytokines, and downregulating the senescence markers P53, P16 and P21. Histological analysis showed marked improvement in ileal architecture and epithelial barrier integrity. SJ‐FUC also mitigated ageing‐associated regenerative decline, as indicated by increased expression of intestinal stem cell‐related markers Lgr5, Ascl2 and Olfm4, elevated numbers of Olfm4‐positive and Ki67‐positive cells in ileal crypts, and restoration of Wnt/β‐catenin signalling. In addition, SJ‐FUC promoted goblet and Paneth cell differentiation. 16S rRNA sequencing further showed that SJ‐FUC remodelled gut microbial composition, characterized by enrichment of beneficial taxa such as Lactobacillus and reduction of potentially detrimental bacteria including Bacteroides . CONCLUSION Sulfated fucans from Saccharina japonica alleviate intestinal ageing by preserving epithelial integrity and restoring regenerative capacity, supporting their potential as functional marine polysaccharides for improving age‐related intestinal dysfunction.