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Am J Physiol Gastrointest Liver Physiol 290: G175-G182, 2006. First published August 18, 2005; doi:10.1152/ajpgi.00272.2005
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LIVER AND BILIARY TRACT

Helicobacter pylori and cholesterol gallstone formation in C57L/J mice: a prospective study

Kirk J. Maurer,1,2 Arlin B. Rogers,1 Zhongming Ge,1 Ashley J. Wiese,1 Martin C. Carey,3,* and James G. Fox1,2,*

Divisions of 1Comparative Medicine and 2Biological Engineering, Massachusetts Institute of Technology, Cambridge; and 3Department of Medicine, Harvard Medical School, and Division of Gastroenterology, Brigham and Women's Hospital and Harvard Digestive Diseases Center, Boston, Massachusetts

Submitted 13 June 2005 ; accepted in final form 16 August 2005

Recently, we demonstrated that cholesterol gallstone-prone C57L/J mice rarely develop gallstones unless they are infected with certain cholelithogenic enterohepatic Helicobacter species. Because the common gastric pathogen H. pylori has been identified in the hepatobiliary tree of cholesterol gallstone patients, we wanted to ascertain if H. pylori is cholelithogenic, by prospectively studying C57L infected mice fed a lithogenic diet. Weanling, Helicobacter spp.-free male C57L mice were either infected with H. pylori SS1 or sham dosed. Mice were then fed a lithogenic diet (1.0% cholesterol, 0.5% cholic acid, and 15% dairy triglycerides) for 8 wk. At 16 wk of age, mice were euthanatized, the biliary phenotype was analyzed microscopically, and tissues were analyzed histopathologically. H. pylori infection did not promote cholesterol monohydrate crystal formation (20% vs. 10%), sandy stone formation (0% for both), or true gallstone formation (20%) compared with uninfected mice fed the lithogenic diet (10%). Additionally, H. pylori failed to stimulate mucin gel accumulation in the gallbladder or alter gallbladder size compared with uninfected animals. H. pylori-infected C57L mice developed moderate to severe gastritis by 12 wk, and the lithogenic diet itself produced lesions in the forestomach, which were exacerbated by the infection. We conclude that H. pylori infection does not play any role in murine cholesterol gallstone formation. Nonetheless, the C57L mouse develops severe lesions of both the glandular and nonglandular stomach in response to H. pylori infection and the lithogenic diet, respectively.

lithogenic; bile; cholesterol crystals; mucin; gastritis



Address for reprint requests and other correspondence: K. J. Maurer, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139 (e-mail: kmaurer{at}mit.edu)




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