Abstract: This study aimed to investigate the ameliorative effects of Morchella esculenta polysaccharides (MEP) on dextran sulfate sodium (DSS)-induced colitis and associated liver injury and to preliminarily explore the underlying mechanisms from the perspectives of gut microbiota alterations and gut-liver axis-related indicators. MEP were prepared and structurally characterized. C57BL/6J mice were divided into a control group, a model group, low- and high-dose MEP groups, an antibiotic pretreatment group, and an antibiotic plus MEP group. Disease activity index (DAI), colon length and histopathology, barrier proteins (occludin and zonula occludens-1 (ZO-1)), serum endotoxin lipopolysaccharide (LPS), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic inflammatory indicators including myeloperoxidase (MPO) content, nuclear factor kappa-B (NF-κB) and tumor necrosis factor-α (TNF-α) protein expression, and serum total bile acids (TBA)), and the hepatic farnesoid X receptor (FXR)/small heterodimer partner (SHP)/cholesterol 7α-hydroxylase (CYP7A1) pathway were assessed. Gut microbiota alterations were analyzed by 16S rRNA sequencing. MEP markedly alleviated body mass loss, diarrhea, and hematochezia, improved colon shortening and mucosal injury, promoted the recovery of goblet cells and the mucus layer, and upregulated occludin and ZO-1 protein expression, indicating restoration of the intestinal barrier. Meanwhile, MEP reduced serum LPS and aminotransferase levels, attenuated hepatic inflammatory responses, and improved bile acid homeostasis, and restored FXR-related signaling pathways to almost normal. Gut microbiota analysis showed that MEP improved the diversity and composition of the gut microbiota and induced corresponding changes in its predicted functional profiles. Notably, under broad-spectrum antibiotic pretreatment, MEP still improved colitis-related indicators, and the combined treatment showed a more pronounced improvement in some colitis- and gut-liver axis-related parameters. In conclusion, MEP ameliorates DSS-induced colitis and associated liver injury by enhancing the intestinal barrier, reducing gut-derived endotoxin translocation into the bloodstream, and modulating hepatic FXR signaling and bile acid metabolism. Its protective effects may not be entirely dependent on the gut microbiota, and can be enhanced by its synergism with antibiotic pretreatment. These findings provide a basis for the mechanistic elucidation, development and application of edible and medicinal fungal polysaccharides as functional factors for gut health.

Key words: Morchella esculenta polysaccharides; colitis; intestinal barrier; gut-liver axis; direct host effect; gut microbiota