Detection of Helicobacter hepaticus in Human Bile Samples of Patients with Biliary Disease

Abstract

Background:Since the discovery of Helicobacter pylori, various enterohepatic Helicobacter spices have been detected in the guts of humans and animals. Some enterohepatic Helicobacters have been associated with inflammatory bowel disease or liver disease in mice. However the association of these bacteria with human diseases remains unknown.Materials and Methods:We collected 126 bile samples from patients with cholelithiasis, cholecystitis, gallbladder polyp, and other nonbiliary diseases. Samples were screened for the presence of enterohepatic Helicobacter spp. using cultures, nested PCR, or in situ hybridization. We tested for antibodies to H. pylori and H. hepaticus by Western blot analysis.Results:Attempts at cultivation were unsuccessful. However, H. hepaticus was detected in bile samples with nested PCR whereas H. bilis was not. Helicobacter hepaticus in the bile was confirmed by in situ hybridization, but H. hepaticus from bile samples was coccoid in appearance. We detected immunoglobulin G antibodies to H. hepaticus in bile samples by Western blotting. Helicobacter hepaticus was detected in 40 (32%) of total 126 samples as H. hepaticus positive if at least one of the three methods with nested PCR, in situ, or Western blotting. Patients with cholelithiasis (41%) and cholecystitis with gastric cancer (36%) had significantly higher (p = .029) prevalence of H. hepaticus infection than samples from patients with other diseases.Conclusion:Helicobacter hepaticus may closely associate with diseases of the liver and biliary tract in humans.

Role of Bacteria in Oncogenesis

“…Controls have typically comprised subjects with biliary tract diseases such as gallstones or cholecystitis. Since these diseases have also been linked to enterohepatic Helicobacter, the use of these patients as controls may be inadequate (98). With these caveats, there has been wide variability in the study findings, from no association to a 6-fold increase in the odds of gallbladder cancer with Helicobacter infection.…”

“…Eight studies of humans have evaluated the presence of Helicobacter species in biliary tracts of cancer patients versus controls. These studies have had significant differences in their methods of bacterial detection, including culture, DNA amplification, and immunohistochemistry (58,98). Controls have typically comprised subjects with biliary tract diseases such as gallstones or cholecystitis.…”

Investigation of the Mechanisms by WhichListeria monocytogenesGrows in Porcine Gallbladder Bile

“…and commensal organisms (commensal E. coli and Lactobacillus salivarius) have been associated with human gallbladder infection (cholecystitis) (1,19,40,51). Bacterial colonization of the gallbladder has also been implicated in gallstone formation, although a direct causal link has not been definitively established (30).…”

Helicobacter pyloriinfection does not promote hepatocellular cancer in a transgenic mouse model of hepatitis C virus pathogenesis

“…(EHS) may be involved in hepatobiliary diseases of humans. 15,[36][37][38][39] Although H. hepaticus was not detected in the stools of HCV or hepatitis B virus patients with HCC, a previous study from our laboratory indicated that H. hepaticus promoted liver cancer in B6C3F1-Tg(Alb1-HCVN)35Sml mice and also promoted aflatoxin-induced liver cancer in C3H/HeNCr mice with persistent intestinal colonization of H. hepaticus, despite the lack of the organism in the liver. 22,40 The occurrence of HCCs in H. pylori-infected and uninfected HT and WT mice in our study is consistent with the natural susceptibility of aged B6C3F1 male mice to liver tumors.…”