Given the escalating severity of colitis caused by Salmonella infection and the growing challenge of drug resistance, there is an urgent demand for novel and effective treatment strategies with minimal side effects. Herein, we explored the potential therapeutic effects of polysaccharides on Ulcerative Colitis (UC). Our results showed that both purified polysaccharide from Dendrobium devonianum (DVP-1) and Crude polysaccharides from Dendrobium devonianum (CP) pre-treatment could prevent colon shortening and spleen enlargement, and alleviate colonic tissue damage. Western blot and RT-qPCR analyses revealed that DVP-1 and CP downregulated pro-inflammatory mediators while upregulating the expression of the anti-inflammatory mediator and tight junction proteins. Besides, 16S rRNA sequencing analysis showed that DVP-1 modulated gut dysbiosis by increasing the relative abundance of ClostridiumXlVa, and reducing the relative abundance of Alloprevotella. Additionally, DVP-1 and CP significantly increased the concentrations of tryptophan metabolites while decreasing purine metabolites. Taken together, these findings suggest that DVP-1 and CP yield potential benefits in alleviating UC primarily through restoring intestinal barrier function and regulating intestinal microbiota.
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