Inflammatory bowel diseases are associated with complex shifts in microbiota composition. However, it remains unclear whether specific subsets of commensal bacteria induce inflammatory bowel diseases in genetically susceptible hosts. In this study, we found that deficiency of the E3 ligase Itch, which leads to spontaneous colitis and rectal prolapse, is associated with alteration of the gut microbiota. 16S rRNA sequencing showed expansion of colitogenic sp. in Itch mice. Treatment with broad-spectrum antibiotics substantially reduced colonic inflammation in Itch mice. Microbiota of Itch mice failed to induce spontaneous colitis upon transfer to Itch mice but aggravated chemically induced colitis. Furthermore, we found that , which is expanded in Itch mice, was sufficient to induce colon inflammation in Itch mice.