Fucosylated chondroitin sulfate alleviates colonic barrier dysfunction in Parkinson’s disease via epithelial cell modulation and microecology restoration

Gastrointestinal disturbances frequently precede motor dysfunction and the hallmark pathological features of Parkinson's disease (PD). Fucosylated chondroitin sulfate (fCS- Ib ), a polysaccharide derived from the sea cucumber Isostichopus badionotus , has shown potential in preventing PD pathologies induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Building on this research, we found that fCS- Ib mitigated MPTP-induced gastrointestinal dysfunction. It reduced colonic inflammation by decreasing secretory immunoglobulin A and calprotectin levels, extending gastrointestinal transit time, decreasing intestinal permeability, and preventing colon shortening and inflammatory cell infiltration. Compared to the MPTP group, fCS- Ib preserved goblet cell function and maintained epithelial tight junction integrity in the colon. Our findings suggest that fCS- Ib protected the colonic barrier by binding to colon epithelial cells, exhibiting anti-inflammatory effects, and inhibiting TLR4/β-Catenin signaling. Additionally, fCS- Ib modulated gut bacteria and metabolites, increasing Muribaculaceae and reducing Staphylococcaceae . These results indicate that fCS- Ib holds promise as a dietary intervention for PD treatment by alleviating gastrointestinal dysfunction. • fCS- Ib ameliorates gastrointestinal dysfunction in an MPTP-induced PD model. • fCS- Ib preserves colonic goblet cell function and epithelial tight junctions. • fCS- Ib polysaccharide demonstrates specific binding to colonic epithelial cell. • fCS- Ib protects colonic barrier integrity by modulation TLR4/β-Catenin signaling. • fCS- Ib treatment restores beneficial gut microbiota and associated metabolites.