Polysaccharide-rich fractions from Enteromorpha prolifera improve hepatic steatosis and gut barrier integrity in high-fat diet-induced obese mice linking to modulation of gut microbiota

Polysaccharides from Enteromorpha prolifera (EP) possess important benefits in the management of obesity and associated metabolic diseases, but to date, the underlying mechanism linking this alleviative effect of EP to gut microbiota remains obscure. This study aimed to investigate the effects of EP in improving lipid metabolism disorders and intestinal barrier disruption in mice with high-fat diet (HFD), and its association with modulation of gut microbiota. C57BL/6 mice were fed a control diet or a HFD with or without 5% EP for 12 weeks. Factors related to lipid metabolism, insulin signaling and intestinal barrier integrity, as well as the involvement of gut microbiota and metabolites, were measured. EP supplementation reduced HFD-induced adiposity and mitigated insulin resistance, hepatic steatosis and elevation of serum lipopolysaccharides (LPS). HFD impaired intestinal barrier integrity while improved due to EP. Moreover, EP administration ameliorated HFD-induced gut dysbiosis, as revealed by the increased short-chain fatty acid (SCFA)-producing bacteria (e.g., Bacteroides, Parabacteroides, Alloprevotella, and Ruminococcus) and gut barrier-protective Akkermansia muciniphila and decreased endotoxin-producing bacteria (e.g., Desulfovibrionaceae and Bilophila), accompanied by enrichment in intestinal SCFA content and reduction in circulating LPS level. The change of dominant bacterial genera is significantly corre-lated with improved metabolic profiles and intestinal permeability induced by EP. In conclusion, our results indicate that EP can attenuate HFD-induced metabolic disorders along with restoration of gut barrier integrity and lowering of circulating endotoxin, and these improvements are associated with modulation of gut microbiota composition and related metabolites. These data deepen mechanistic understanding of the anti-obesity and metabolic improving effects of EP.