Abstract Mounting evidence suggests that gut microbiota contributes to the pathogenesis of inflammatory bowel disease (IBD). However, the identity of disease-associated pathobionts is unknown. Recent studies showed that patients with IBD are colonized by atypical bacterial members, particularly those residing in the oral cavity (e.g., Enterobacteriaceae, Pasteurellaceae, Fusobacteriaceae, and Veillonellaceae). Given that patients with IBD often accompanied by oral inflammation and/or oral dysbiosis, it is conceivable that oral disease (inflammation, dysbiosis) may in turn impact on the development of intestinal pathology. In this study, we demonstrate that periodontal inflammation exacerbates colitis in mice. Periodontitis in mice was induced by insertion of the oral ligature. Colitis was induced by the administration of dextran sulfate sodium (DSS). Mice with periodontitis developed more severe DSS-induced colitis compared to those without periodontitis. During periodontitis, Enterobacteriaceae were expanded in the oral cavity. Amassed Enterobacteriaceae of oral origin were then ingested and ectopically colonized the colon. Gut colonization by the oral Enterobacteriaceae elicits the activation of the inflammasome and promotes inflammation. Taken together, inflammation in the oral mucosa may foster the abnormal expansion of oral pathobionts whose ectopic gut colonization aggravates IBD.