Lyophyllum decastes-Derived Polysaccharides Alleviate DSS-Induced Colitis in Mice by Suppressing Inflammation, Enhancing Intestinal Barrier Integrity, and Restoring Gut Microbiota Homeostasis

Eslam Fahd¹Yamina Alioui²Jamalat Yazeed²Natheer Wahan²Ahmed Bashah²Ali Al- Waqeerah²AAMNA ATTA²Yuxin Sun²Yi Xin²Bin Feng^2*Liang Wang^2*Weifeng Mao^2*

• ¹Biochemistry and molecular biology department, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China, Dalian Medical University, Dalian, China
• ²Dalian Medical University, Dalian, China

Introduction: Inflammatory bowel disease (IBD), including ulcerative colitis (UC), is characterized by disturbances in the intestinal barrier, immune system dysfunction, and an altered gut microbiota composition. Lyophyllum decastes, a medicinal mushroom known for its bioactive polysaccharides, has shown potential anti-inflammatory properties. However, its therapeutic effects on ulcerative colitis have not been studied. This study investigates the effects of L. decastes polysaccharides (LDP) on dextran sulfate sodium (DSS)-induced colitis in mice.Ulcerative colitis was induced in BALB/c mice by administering 3% DSS in drinking water for 7 days. Mice were then treated orally with LDP at doses of 200 or 400 mg/kg for 14 days. Disease activity index (DAI), histopathological analysis, cytokine levels, myeloperoxidase (MPO) activity, tight junction protein expression (occludin and ZO-1), and gut microbiota composition were assessed.Results and Discussion: LDP treatment significantly reduced DAI scores and preserved colonic histological structure. It modulated cytokine levels, decreasing pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and increasing anti-inflammatory cytokines (IL-10, IL-4, TGF-β). Additionally, LDP improved intestinal barrier function by reducing MPO activity and enhancing occludin and ZO-1 expression. 16S rRNA sequencing revealed a significant restoration of gut microbiota diversity, with an increase in beneficial bacteria Muribaculaceae, Lactobacillus, and Lachnospiraceae, and a reduction in pathogenic bacteria Escherichia-Shigella. these findings suggest that LDP exhibits therapeutic effects in DSS-induced colitis through anti-inflammatory properties, enhancement of intestinal barrier function, and modulation of gut microbiota. These findings suggest that LDP may serve as a promising novel therapeutic agent for the management of ulcerative colitis.