Abstract:[Objective] To investigate the effect of synbiotic containing Bacillus coagulans and lactulose on clinical symptoms, intestinal morphology and microbiota in mice with dextran sodium sulfate (DSS)-induced ulcerative colitis.[Methods] A total of 24 7-week-old male C57/BL6 mice with initial body weight of (22.96±1.87) g were randomized into 4 groups (6 in each):control group (CON), DSS group (2.5% DSS in water for 5 days), SYN-P group (gastric gavage of oral synbiotic once a day for 7 days before DSS administration), and SYN-T group (gastric gavage of oral synbiotic once a day for 7 days after DSS administration). After 7-day pre-feeding period and 19-day experimental period, the mice were euthanized and samples were collected.[Results] On the 10th day in the experimental period, except CON group, mice began to lose weight, among which DSS group had the fastest weight loss and the highest disease activity index (DAI). After DSS treatment was terminated (14th day), the body weight of SYN-P and SYN-T groups gradually returned to normal level, while that of DSS group did not. Compared with CON group, DSS group showed decrease in colon length (P<0.05) and increase in liver and spleen indexes (liver or spleen weight/body weight) (P<0.05), while SYN-T group demonstrated rise of liver index (P<0.05). As for the histomorphology, the height of colon villi in CON group was larger than that in DSS and SYN-P groups (P<0.05), and colonic crypt depth in DSS group was larger than that in the other three groups (P<0.05). The villus height-to-crypt depth ratio in DSS group was significantly smaller than that in SYN-P and SYN-T groups (P<0.05). As to the caecal microflora, the diversity indexes (ACE, Chao1, Shannon, and Anova) of microflora changed (P<0.05). At the phylum level, the relative abundance of Desulfobacterota and Deferribacteres in SYN-P group decreased (P<0.05) and that of Deferribacteres in SYN-T group reduced (P<0.05) compared with that in DSS group. At the genus level, the relative abundance of 13 dominant genera such as Enterococcus changed. PICRUSt analysis showed that the KEGG pathway of carbohydrate metabolism was up-regulated in SYN-P and SYN-T groups compared with that in CON and DSS groups (P<0.05). In addition, 11 pathways at KEGG level 3, including fructose and mannose metabolism, were affected.[Conclusion] Synbiotic containing B. coagulans and lactulose can relieve clinical symptoms in mice with DSS-induced ulcerative colitis, improve the intestinal morphology, and reduce the relative abundance of Desulfobacterota and Deferribacteres that caused inflammatory response in the intestinal tract through prevention and treatment.