Effects of dietary fucoidan and exercise on the gut microbiome, fecal metabolome, and tumor-related responses in a murine colorectal cancer model

Dietary fucoidan, a sulfated polysaccharide derived from brown seaweed, has attracted increasing interest for its potential to influence gut microbial and metabolic responses. However, the individual and combined effects of dietary fucoidan and exercise on host–microbiome interactions during colorectal cancer development remain incompletely understood. In this preventive study, mice received fucoidan at 300 mg/kg (F1) or 600 mg/kg (F2), alone or in combination with low-intensity exercise at 12 m/min for 30 min or moderate-intensity exercise at 15 m/min for 40 min, for six weeks before MC38 tumor induction. The interventions were associated with distinct changes in gut microbial composition and fecal metabolic profiles. Notably, the X2F1 group showed enrichment of Lactobacillus murinus together with alterations in bacterial taxa linked to short-chain fatty acid metabolism. Metabolomic analysis further revealed changes in amino acid, bile acid, and central carbon metabolism, indicating coordinated microbial and metabolic remodeling. The X2F1 group also showed a marked reduction in tumor burden, while low-dose fucoidan alone produced a clear tumor-associated response and broad changes across microbial and metabolic outcomes. Tumor gene-expression analysis showed increased p53 and Bax expression and reduced Bcl-2 and Ki67 expression in several intervention groups, consistent with apoptosis- and proliferation-related molecular responses. These findings suggest that dietary fucoidan, alone or in combination with exercise, is associated with coordinated changes in the gut microbiome, fecal metabolome, tumor burden, and tumor-related molecular profiles in an MC38 colorectal cancer model.