Cholangiohepatitis and inflammatory dowel disease induced by a novel urease-negative Helicobacter species in A/J and Tac : ICR : HascidfRF mice

Helicobacter bills and H. hepaticus, both urease-positive intestinal helico bacters of mice, have been shown experimentally to induce proliferative typ hlocolitis in scid mice. We recently isolated a urease-negative Helicobacte r sp. (H. sp.) that also induced proliferative typhlocolitis in pilot studi es in scid mice, To determine the pathogenic potential of H. sp, in immunoc ompromised and immunocompetent mice, 5-week old male A/J or Tac:lcr:Ha(ICR) -scidfRF mice were inoculated by intraperitoneal (IP) injection with simila r to 3 x 10(7) colony-forming units (CFU) of H. so, Mice were necropsied at various time points postinoculation (PI), Sham-inoculated mice had no clin ical, gross, or histopathological lesions, In contrast, scid mice inoculate d IP with H. sp. had severe hemorrhagic diarrhea and decreased weight gain at 2, 7, and 18 weeks postinoculation (PI), with severe proliferative typhl ocolitis, phlebothrombosis, and hepatitis. A/J mice had no clinical signs, but had mild to moderate proliferative typhlocolitis and moderate to marked cholangiohepatitis at 7 and 24 weeks PI, A/J mice infected with H. sp. dev eloped robust immune responses of a predominant Th1 type. This report demon strates that infection with a urease-negative helicobacter can cause inflam matory bower disease (IBD) and hepatitis in scid and immunocompetent A/J mi ce, These results provide a new model of IBD and cholangiohepatitis associa ted with a specific urease-negative, novel H. species.