Although oral bacteria-associated systemic diseases have been reported, association between Streptococcus mutans, pathogen of dental caries, and ulcerative colitis (UC) has not been reported. We investigated the effect of various S. mutans strains on dextran sodium sulfate (DSS)-induced mouse colitis. Administration of TW295, the specific strain of S. mutans, caused aggravation of colitis; the standard strain, MT8148 did not. Localization of TW295 in hepatocytes in liver was observed. Increased expression of interferon-γ in liver was also noted, indicating that the liver is target organ for the specific strain of S. mutans-mediated aggravation of colitis. The detection frequency of the specific strains in UC patients was significantly higher than in healthy subjects. Administration of the specific strains of S. mutans isolated from patients caused aggravation of colitis. Infection with highly-virulent specific types of S. mutans might be a potential risk factor in the aggravation of UC.