Human fecal fermentation of high/low-molecular weight exopolysaccharides from a medicinal fungus Cs-HK1 and anti-inflammatory protection on gut barrier function

The exopolysaccharides (EPS) produced by the Cordyceps sinensis Cs-HK1 fungus have shown multiple bioactivities and potential health benefits in previous studies. This study was to assess the prebiotic properties and the protective effects on gut barrier of EPS and human fecal fermentation products. Two EPS fractions with different molecular weight (MW) and composition, EPS-LM (4.5 × 10⁶ Da) and EPS-HM (9.4 × 10⁷ Da) were fractionated through ethanol precipitation. Both EPS fractions were found highly resistant to digestive enzymes and gastric acid but highly fermentable in human fecal culture. Over 48 h-fecal fermentation, the EPS were effectively degraded and utilized by the intestinal microbiota, increasing the production of short-chain fatty acids (SCFAs: acetic, propionic and butyric acid). The consumption of carbohydrates and the production of SCFAs varied slightly between the two EPS fractions. The fecal fermentation of EPS increased the abundance of Actinobacteria, Bacteroidetes and Faecalibacterium that are associated with improved gut health and metabolic function. In lipopolysaccharide (LPS)-stimulated Caco-2/Raw264.7 co-culture model, the fecal fermentation products of EPS showed potential protective effect against inflammatory damage of gut barrier function. The findings suggest that EPS fractions may serve as promising therapeutic agents for enhancing gut barrier function and gut health through modulation of gut microbiota.