Spontaneous Inflammatory Bowel Disease in Multiple Mutant Mouse Lines: Association with Colonization by Helicobacter hepaticus

Both genetic and microbial factors are thought to play a role in the development of inflammatory bowel disease (IBD): however, no causative microbial agent has been clearly defined for humans or animals. Normal flora or previously unrecognized intestinal pathogens may contribute to the development of disease in susceptible hosts. A newly recognized murine Helicobacter, H. hepaticus, causes hepatitis in mice and in one strain of mice is linked to liver cancer. This study investigates the association between colonization of the lower intestinal tract of multiple genetically altered lines of mice with H. hepaticus, and the occurrence of IBD. Rectal prolapse noted clinically in multiple genetically altered mouse lines was evaluated for the presence of H. hepaticus and histologic evidence of IBD. Fifty-five mice representing 11 different genetic alterations were evaluated. H. hepaticus was detected in 85% of mutant mice with rectal prolapse. Histologic evidence of proliferative typhlitis, colitis or proctitis was present in 65% of the animals examined, 89% of which were positive for H. hepaticus as detected by species specific PCR. The presence of H. hepaticus in association with IBD in multiple lines of genetically altered mice suggests further studies are needed to test experimentally the role H. hepaticus plays in the development of IBD in susceptible mice. Additionally, specific mutant mouse lines infected with H. hepaticus in this study may provide additional models for elucidation of microbial and genetic factors in the pathogenesis of IBD.