IntroductionUlcerative colitis (UC) is an inflammatory disease of the intestinal tract with unknown etiology. Both genetic and environmental factors are involved in the occurrence and development of UC. Understanding changes in the microbiome and metabolome of the intestinal tract is crucial for the clinical management and treatment of UC. MethodsHere, we performed metabolomic and metagenomic profiling of fecal samples from healthy control mice (HC group), DSS (Dextran Sulfate Sodium Salt) -induced UC mice (DSS group), and KT2-treated UC mice (KT2 group). Results and DiscussionIn total, 51 metabolites were identified after UC induction, enriched in phenylalanine metabolism, while 27 metabolites were identified after KT2 treatment, enriched in histidine metabolism and bile acid biosynthesis. Fecal microbiome analysis revealed significant differences in nine bacterial species associated with the course of UC, including Bacteroides, Odoribacter, and Burkholderiales, which were correlated with aggravated UC, and Anaerotruncus, Lachnospiraceae, which were correlated with alleviated UC. We also identified a disease-associated network connecting the above bacterial species with UC-associated metabolites, including palmitoyl sphingomyelin, deoxycholic acid, biliverdin, and palmitoleic acid. In conclusion, our results indicated that Anaerotruncus, Lachnospiraceae, and Mucispirillum were protective species against DSS-induced UC in mice. The fecal microbiomes and metabolomes differed significantly among the UC mice and KT2-treated and healthy-control mice, providing potential evidence for the discovery of biomarkers of UC.