Helicobacter hepaticus and Helicobacter bilis: proinflammatory modulators of enterohepatic disease

Using Steiner’s silver stain a bacterium with spiral to curved morphology was observed in livers of control A/JCr mice with hepatitis, hepatic adenomas and hepatocellular carcinomas1. A Gram-negative bacterium with bipolar, single-sheathed flagella, isolated from these mice with diseased livers, maintained on a long-term carcinogenicity study, was characterized and named H. hepaticus 2. Since its original observation in A/JCr mice in 1991, H. hepaticus is now known to be prevalent in many mouse colonies, commercial and academic, throughout the world3. In addition to A/JCr mice, H. hepaticus causes hepatitis in BALB/cCr, SJL/NCr, SCID/NCr, C3H/ HeNCr mice and AxB recombinant strains. Like AJ/CR mice, H. hepaticus infection in B6C3F1 and AxB mice is associated with liver cancer. Because H. hepaticus’ ecological niche is the lower bowel, and the organism can also be readily isolated from the faeces, faecal-oral transmission is suspected. For example, H. hepaticus was isolated from either the caecum or the colon of 100% of A/JCr mice surveyed during a longitudinal study4. Thus, for routine diagnosis of H. hepaticus infection in infected mice, isolation should be attempted from the distal part of the intestine, not the liver parenchyma. The persistent nature of the infection, usually without overt clinical signs in wild-type mice, may in part contribute to the high prevalence of H. hepaticus in commercial and academic mouse colonies3,5. Recently, because of the negative impact of Helicobacter infections on biomedical research, considerable effort has been expended to derive Helicobacter-free colonies at several commercial vendors in the United States.