Abstract: To explore the mechanism of the intestinal microecology regulation by polysaccharide prebiotics, ELISA, histopathologic analysis, immunohistochemical analysis, 16S rRNA high-throughput sequencing, and gas chromatography-mass spectrometry were applied to investigate the effects of fermented polysaccharides on changes in the intestinal microbiota and short-chain fatty acids (SCFAs) in mice with dextran sulfate sodium (DSS)-induced colitis model and their relationship with the level of intestinal inflammation and barrier protein expression. It was found that fermented Lycium barbarum polysaccharides (FLBP) significantly reduced intestinal inflammation level, improved colonic tissue structure, up-regulated the expression of tight junction proteins Claudin-1 and ZO-1, and significantly increased the content of intestinal SCFAs in mice. Gut bacteria analyses showed that FLBP enriched intestinal Dubosiella and Akkermansia in mice and decreased the abundance of Turicibacter, Faecalibaculum, and Escherichia-Shigella. Results showed that remodeled Dubosiella activated by FLBP played a dominant role in ameliorating colitis by significantly increasing SCFAs content, improving intestinal barrier and reducing intestinal inflammation. The study aimed to provide a safer and better option for the amelioration of colitis and to provide a theoretical basis for the development of functional foods with FLBP.