Abstract
Several Helicobacter species are known to colonize the biliary tract in animals and have been identified in the gallbladder bile of a high proportion of Chilean patients with gallbladder cancer. In this study, we tried to examine the presence of Helicobacter species in the bile to know their participation in the development of extrahepatic biliary diseases. DNA was extracted from 57 bile samples from 30 patients with benign biliary diseases (cholecystolithiasis and choledochocystolithiasis), 6 malignant biliary diseases (gallbladder cancer and common bile duct cancer), and 21 nonbiliary diseases. The presence of Helicobacter genus-, H. pylori-, H. hepaticus-, and H. bilis-specific 16S rRNA genes, the H. pylori urease A gene, and the H. pylori 26K protein gene in the bile was determined by PCR and sequencing analysis. Helicobacter genus DNA (shorter amplicons, 400 bp) was statistically frequently detected in biles from 53% (16/30) and 86% (5/6) of benign and malignant biliary diseases, compared with 9% (2/21) of nonbiliary diseases, but longer amplicons (1200 bp) were not detectable in any samples. The H. pylori urease A gene (nested amplicon) was also frequently found in bile, whether benign, malignant, or control, though neither H. pylori 16S rRNA nor the 26K protein gene was detectable in any bile samples. H. bilis-16S rRNA genes were detectable in only two cases. H. hepaticus was not detectable in any samples. DNA fragments of Helicobacter species other than H. pylori, H. hepaticus, and H. bilis are commonly detectable in the bile of patients with extrahepatic biliary diseases, whether benign or malignant, implying that the Helicobacter genus may be directly or indirectly involved in the pathogenesis of these diseases.
Similar content being viewed by others
References
Marshall BJ, Warren JR: Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1:1311–1315, 1984
Watanabe T, Tada M, Nagai H, Sasaki S, Nakao M: Helicobacter pylori infection induces gastric cancer in mongolian gerbils. Gastroenterology 115:642–648, 1998
Parsonnet J, Friedman GD, Vandersteen DP, et al.: Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 325:1127–1131, 1991
Fox JG, Dewhirst FE, Shen Z, et al.: Hepatic Helicobacter species identified in bile and gallbladder tissue from Chileans with chronic cholecystitis. Gastroenterology 114:755–763, 1998
Lin TT, Yeh CT, Wu CS, Liaw YF: Detection and partial sequence analysis of Helicobacter pylori DNA in the bile samples. Dig Dis Sci 40:2214–2219, 1995
O’Rourke JL, Grehan M, Lee A: Non-pylori Helicobacter species in humans. Gut 49:601–606, 2001
Roosendaal R, Kuipers EJ, Vandenbroucke-Grauls CM, Kusters JG: Helicobacter species are not detectable by 16S rDNA PCR in bile from Dutch patients with common bile duct stones. Digestion 66:89–91, 2002
Nilsson HO, Castedal M, Olsson R, Wadstrom T: Detection of Helicobacter in the liver of patients with chronic cholestatic liver diseases. J Physiol Pharmacol 50:875–882, 1999
Rudi J, Rudy A, Maiwald M, Stremmel W: Helicobacter sp. are not detectable in bile from German patients with biliary disease. Gastroenterology 116:1016–1017, 1999
Mendez-Sanchez N, Pichardo R, et al.: Lack of association between Helicobacter sp colonization and gallstone disease. J Clin Gastroenterol 32:138–141, 2001
Fox JG, Yan LL, Dewhirst FE, et al.: Helicobacter bilis sp. nov., a novel Helicobacter species isolated from bile, livers, and intestines of aged, inbred mice. J Clin Microbiol 33:445–454, 1995
Fox JG, MacGregor JA, Shen Z, Li X, Lewis R, Dangler CA: Comparison of methods of identifying Helicobacter hepaticus in B6C3F1 mice used in a carcinogenesis bioassay. J Clin Microbiol 36:1382–1387, 1998
Nilsson HO, Taneera J, Castedal M, Glatz E, Olsson R, Wadstrom T: Identification of Helicobacter pylori and other Helicobacter species by PCR, hybridization, and partial DNA sequencing in human liver samples from patients with primary sclerosing cholangitis or primary biliary cirrhosis. J Clin Microbiol 38:1072–1076, 2000
Fukuda K, Kuroki T, Tajima Y, et al.: Comparative analysis of Helicobacter DNAs and biliary pathology in patients with and without hepatobiliary cancer. Carcinogenesis 23:1927–1931, 2002
Bulajic M, Maisonneuve P, Schneider-Brachert W, et al.: Helicobacter pylori and the risk of benign and malignant biliary tract disease. Cancer 95:1946–1953, 2002
Matsukura N, Yokomuro S, Yamada S, et al.: Association between Helicobacter bilis in bile and biliary tract malignancies: H. bilis in bile from Japanese and Thai patients with benign and malignant diseases in the biliary tract. Jpn J Cancer Res 93:842–847, 2002
Chen W, Li D, Cannan RJ, Stubbs RS: Common presence of Helicobacter DNA in the gallbladder of patients with gallstone diseases and controls. Dig Liver Dis 35:237–243, 2003
Fallone CA, Tran S, Semret M, Discepola F, Behr M, Barkun AN: Helicobacter DNA in bile: correlation with hepato-biliary diseases. Aliment Pharmacol Ther 17:453–458, 2003
Kawaguchi M, Saito T, Ohno H, et al.: Bacteria closely resembling Helicobacter pylori detected immunohistologically and genetically in resected gallbladder mucosa. J Gastroenterol 31:294–298, 1996
Labigne A, Cussac V, Courcoux P: Shuttle cloning and nucleotide sequences of Helicobacter pylori genes responsible for urease activity. J Bacteriol 173:1920–1931, 1991
Fox JG, Dewhirst FE, Tully JG, et al.: Helicobacter hepaticus sp. nov., a microaerophilic bacterium isolated from livers and intestinal mucosal scrapings from mice. J Clin Microbiol 32:1238–1245, 1994
Franklin CL, Riley LK, Livingston RS, Beckwith CS, Besch-Williford CL, Hook RR Jr.: Enterohepatic lesions in SCID mice infected with Helicobacter bilis. Lab Anim Sci 48:334–339, 1998
Ward JM, Anver MR, Haines DC, Benveniste RE: Chronic active hepatitis in mice caused by Helicobacter hepaticus. Am J Pathol 145:959–968, 1994
Ward JM, Fox JG, Anver MR, et al.: Chronic active hepatitis and associated liver tumors in mice caused by a persistent bacterial infection with a novel Helicobacter species. J Natl Cancer Inst 86:1222–1227, 1994
Harada K, Ohira S, Isse K, et al.: Lipopolysaccharide activates nuclear factor-kappaB through toll-like receptors and related molecules in cultured biliary epithelial cells. Lab Invest 83:1657–1667, 2003
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kobayashi, T., Harada, K., Miwa, K. et al. Helicobacter Genus DNA Fragments Are Commonly Detectable in Bile from Patients with Extrahepatic Biliary Diseases and Associated with Their Pathogenesis. Dig Dis Sci 50, 862–867 (2005). https://doi.org/10.1007/s10620-005-2654-1
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10620-005-2654-1