Sulfated Polysaccharide from Sea Cucumber and its Depolymerized Derivative Prevent Obesity in Association with Modification of Gut Microbiota in High‐Fat Diet‐Fed Mice

SCOPE: Sulfated polysaccharide from sea cucumber (SCSP), Stichopus japonicus, has been shown to prevent diverse diseases, but little is known about its effects on obesity and gut microbiota in mice fed a high-fat diet (HFD). METHODS AND RESULTS: ) for 8 weeks. The results show that both SCSP and d-SCSP reduce body weight, fat and liver hypertrophy, insulin resistance, and serum lipid and inflammatory cytokine levels in HFD-fed mice. Moreover, SCSP and d-SCSP not only prevent HFD-induced gut disorder, as indicated by the enriched probiotic Akkermansia and reduce endotoxin-bearing Proteobacteria, but also improve the SCFAs and endotoxin (LPS) levels and gut tissue index. Spearman's correlation analysis reveals that several specific genera are strongly correlated with obesity-related indexes. In addition, the inhibitory effect of d-SCSP on fat accumulation is more effective than that of SCSP, which may be related to their different regulation of the gut microbiota. CONCLUSIONS: These findings suggest that SCSP can prevent diet-induced obesity and its associated diseases by modulating the gut microbiota and improving microbial metabolites and gut tissue, and its effects can be enhanced by free-radical depolymerization.