Functional fractions of Astragalus polysaccharides as a potential prebiotic to alleviate ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine that is significantly influenced by an imbalance in the gut microbiota. Astragalus membranaceus, particularly its polysaccharide components, has shown therapeutic potential for the treatment of UC, although the specific active constituents and their mechanistic pathways remain to be fully elucidated. In this study, we investigated two molecular weight fractions of Astragalus polysaccharides (APS), APS1 (Mw < 10 kDa) and APS2 (10 kDa < Mw < 50 kDa), isolated by ultrafiltration, focusing on their prebiotic effects, effects on UC, and the underlying mechanism. Our results showed that both APS1 and APS2 exhibit prebiotic properties, with APS1 significantly outperforming APS2 in ameliorating UC symptoms. APS1 significantly attenuated weight loss and UC manifestations, reduced colonic pathology, and improved intestinal mucosal barrier integrity. In addition, APS1 significantly reduced the levels of inflammatory cytokines in the serum and colonic tissue, and downregulated colonic chemokines. Furthermore, APS1 ameliorated dextran sulfate sodium salt (DSS)-induced intestinal dysbiosis by promoting the growth of beneficial microbes and inhibiting the proliferation of potential pathogens, leading to a significant increase in short-chain fatty acids. In conclusion, this study highlights the potential of APS1 as a novel prebiotic for the prevention and treatment of UC.