ABSTRACT Gut microbiota has become a key therapeutic target for inflammatory bowel disease (IBD). Astragalus polysaccharides (AP), the main active components of Astragalus membranaceus, can prevent experimental colitis, but their mechanisms remain unclear. This study investigated the therapeutic effect of AP on DSS‐induced colitis and its mechanism of attenuation. AP significantly improved colitis by increasing body weight and colon length, reducing histological injury, and lowering the disease activity index (DAI). AP inhibited proinflammatory cytokines (IL‐6, IL‐17A, IL‐22, IL‐23), upregulated anti‐inflammatory cytokines (IL‐10, TGF‐β) in colon tissue, and increased fecal SCFA levels. AP also reshaped gut microbiota by decreasing Proteobacteria, Verrucomicrobia, Allobaculum , Turicibacter , and Akkermansia , while enriching Firmicutes, Bacteroidetes, Lactobacillus , Lachnospiraceae , Ruminococcus , and Oscillospira . These enriched genera positively correlated with IL‐10, TGF‐β, and SCFAs, and negatively with IL‐6, IL‐17A, and IL‐23. KEGG analysis showed that AP restored metabolic pathways disrupted during colitis. Overall, AP protected against DSS‐induced colitis by modulating gut microbial composition, metabolism, and immune responses. Importantly, ABX + AP experiments confirmed that the therapeutic effect of AP depends on gut microbiota. These findings indicate that AP alleviates colitis by remodeling the gut microbiota and may serve as a promising microbiome‐based therapy for ulcerative colitis.
Khan et al. (Mon,) studied this question.