Integrated multi-omics profiling of gut microbiome and metabolome in ulcerative colitis insights from the Iranian population

Ulcerative colitis is a chronic inflammatory disorder of the gastrointestinal tract associated with substantial alterations in gut microbial composition and metabolic function. This study investigated intestinal dysbiosis in affected individuals using microbial profiling, genetic analysis, metabolomic assessment, and pathway modeling. Patients showed reduced microbial diversity, loss of beneficial species such as Faecalibacterium and Roseburia, and increased abundance of inflammatory taxa, including Escherichia coli and Fusobacterium, alongside a marked decrease in the Firmicutes-to-Bacteroidetes ratio. Levels of key short-chain fatty acids, particularly butyrate, and protective metabolites such as indole-3-propionic acid were diminished, whereas pro-inflammatory metabolites, including sphingosine, were elevated. Pathway analysis indicated disruptions in tryptophan metabolism and short-chain fatty acid biosynthesis, and species-metabolite networks highlighted antagonistic relationships between inflammatory bacteria and protective metabolites. These findings reveal extensive structural and functional dysbiosis and underscore the potential of microbiome-based therapeutic strategies for managing ulcerative colitis.