Identification of cholelithogenic enterohepatic helicobacter species and their role in murine cholesterol gallstone formation.
OBJECTIVE
Helicobacter spp are common inhabitants of the hepatobiliary and gastrointestinal tracts of humans and animals and cause a variety of well-described diseases. Recent epidemiologic results suggest a possible association between enterohepatic Helicobacter spp and cholesterol cholelithiasis, chronic cholecystitis, and gallbladder cancer. To test this, we prospectively investigated the effects of Helicobacter spp infection in cholesterol gallstone pathogenesis in the highly susceptible C57L/J mouse model.


METHODS
Helicobacter spp-free adult male C57L mice were infected with several different enterohepatic Helicobacter spp or left uninfected and fed either a lithogenic diet or standard mouse chow for 8 and 18 weeks. At the conclusion of the study, bile was examined microscopically and diagnostic culture and polymerase chain reaction were performed.


RESULTS
Mice infected with Helicobacter bilis or coinfected with Helicobacter hepaticus and Helicobacter rodentium and fed a lithogenic diet developed cholesterol gallstones at 80% prevalence by 8 weeks compared with approximately 10% in uninfected controls. Monoinfections with H hepaticus , Helicobacter cinaedi , and H rodentium gave a cholesterol gallstone prevalence of 40%, 30%, and 20%, respectively; the latter 2 groups did not differ significantly from uninfected animals. Neither infected nor uninfected mice fed a chow diet developed cholesterol gallstones.


CONCLUSIONS
These findings, along with prior epidemiologic studies, suggest that Helicobacter spp play a major role in the pathophysiology of cholesterol gallstone formation in mice and perhaps humans.
Maurer
Kirk J
KJ
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. kmaurer@mit.edu
Ihrig
Melanie M
MM
Rogers
Arlin B
AB
Ng
Vivian
V
Bouchard
Guylaine
G
Leonard
Monika R
MR
Carey
Martin C
MC
Fox
James G
JG
D000818:Animals; D001646:Bile / Q000378:metabolism; D001659:Biliary Tract / Q000473:pathology; D002769:Cholelithiasis / Q000209:etiology*; D002784:Cholesterol / Q000378:metabolism*; D004032:Diet; D005704:Gallbladder / Q000473:pathology; D042882:Gallstones / Q000378:metabolism / Q000382:microbiology*; D016998:Helicobacter / Q000235:genetics / Q000502:physiology*; D016481:Helicobacter Infections / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D007422:Intestines / Q000382:microbiology*; D008099:Liver / Q000382:microbiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D013045:Species Specificity
D002784:Cholesterol