Choerospondias axillaris degraded polysaccharides alleviate DSS-induced colitis in mice by modulating the gut microbiota and metabolites

Molecular weight ( Mw ) has been demonstrated to significantly influence the biological activity of polysaccharides; however, its impact on the protective effects on colitis remains unclear. Therefore, this study elucidated the differential protective effects of native Choerospondias axillaris polysaccharide (CAP) and the degraded polysaccharides (DCAP) prepared via an H 2 O 2 -Vc system in a DSS-induced colitis mouse model and explored the underlying mechanisms. Both CAP and DCAP effectively ameliorated colitis symptoms, attenuated histological damage, restored the gene expression levels of ZO-1 , Occludin , and Claudin-1 , downregulated the gene levels of pro-inflammatory cytokines ( IL-6 and TNF-α ), and improved oxidative stress markers. Furthermore, both polysaccharides reversed DSS-induced dysbiosis of the gut microbiota and altered in fecal metabolic profiles. Notably, DCAP exhibited superior effects, with differential metabolites predominantly enriched in linoleic acid metabolism, PPAR signaling pathway, and purine metabolism. These findings provide new insights into the anti-inflammatory mechanism of Choerospondias axillaris polysaccharides, underscoring the critical role of molecular weight in shaping the gut microbiota and its metabolome.