The Carcinogenic Liver Fluke Opisthorchis viverrini is a Reservoir for Species of Helicobacter

Abstract

There has been a strong, positive correlation between opisthorchiasis-associated cholangiocarcinoma and infection with Helicobacter. Here a rodent model of human infection with Opisthorchis viverrini was utilized to further investigate relationships of apparent co-infections with O. viverrini and H. pylori. A total of 150 hamsters were assigned to five groups: i) Control hamsters not infected with O. viverrini; ii) O. viverrini-infected hamsters; iii) non-O. viverrini infected hamsters treated with antibiotics (ABx); iv) O. viverrini-infected hamsters treated with ABx; and v) O. viverrini-infected hamsters treated both with ABx and praziquantel (PZQ). Stomach, gallbladder, liver, colonic tissue, colorectal feces and O. viverrini worms were collected and the presence of species of Helicobacter determined by PCR-based approaches. In addition, O. viverrini worms were cultured in vitro with and without ABx for four weeks, after which the presence of Helicobacter spp. was determined. In situ localization of H. pylori and Helicobacter-like species was performed using a combination of histochemistry and immunohistochemistry. The prevalence of H. pylori infection in O. viverrini-infected hamsters was significantly higher than that of O. viverrini-uninfected hamsters (p≤0.001). Interestingly, O. viverrini-infected hamsters treated with ABx and PZQ (to remove the flukes) had a significantly lower frequency of H. pylori than either O. viverrini-infected hamsters treated only with ABx or O. viverrini-infected hamsters, respectively (p≤0.001). Quantitative RT-PCR strongly confirmed the correlation between intensity H. pylori infection and the presence of liver fluke infection. In vitro, H. pylori could be detected in the O. viverrini worms cultured with ABx over four weeks. In situ localization revealed H. pylori and other Helicobacter-like bacteria in worm gut. The findings indicate that the liver fluke O. viverrini in the biliary tree of the hamsters harbors H. pylori and Helicobacter-like bacteria. Accordingly, the association between O. viverrini and H. pylori may be an obligatory mutualism.

Coinfection with Helicobacter pylori and Opisthorchis viverrini Enhances the Severity of Hepatobiliary Abnormalities in Hamsters

“…In hamsters infected with O. viverrini alone, H. pylori was detected in 50% of the gastric tissues tested but was less prevalent in the hepatobiliary system (25%) than in the HP group, suggesting that oral inoculation with H. pylori permits its transmission to the biliary system with or without the presence of flukes. There appears to be a background level of natural infection of gastric tissue (but not liver tissue) with H. pylori in our hamsters, which was similar to findings in a previously study (11,28). Inoculation with additional H. pylori and/or the presence of worms was associated with the presence of H. pylori in the biliary system.…”

“…The first is by causing gastric injury, facilitating transport to the liver via the bloodstream (29). Second, when inoculated with O. viverrini, H. pylori may be carried into the hepatobiliary system directly by the worms (11). Third, physical obstruction of the bile ducts by O. viverrini infection (30) may lead to increased pressure and a low pH within the biliary tract, which might permit influx of H. pylori from the gastrointestinal tract into the hepatobiliary system.…”

“…The presence of H. pylori in the liver and gallbladder was associated with biliary inflammation and proliferation (10). Recently, H. pylori infection was found to be more prevalent in O. viverrini-infected hamsters than in normal hamsters, suggesting that the parasite in the bile duct is a reservoir of H. pylori and Helicobacter-like bacteria (11). Taken together, these lines of evidence support the hypothesis that H. pylori coinfection with O. viverrini synergistically increases the severity of hepatobiliary abnormalities.…”

Genetic characterization of Helicobacter pylori vacA and cagA genes in Thai gastro-duodenal and hepatobiliary patients

“…Our previously published data showed that cagPAI especially cagA of H. pylori can induce inflammation and disturbance of cell kinetic on hepatobiliary cell lines [31,36,37]. Therefore, we suggest that, in addition to O. viverrini infection, H. pylori may be a co-factor of the O. viverrini pathogenesis in Thai CCA patients as previously described by our colleagues, showing the significant relationship between O. viverrini and H. pylori [38]. However, the association and role of H. pylori in CCA should be further investigated.…”

Human liver flukes

“…(65) . O. viverrini infection may also cause changes in bile acid composition that reduce alkalinity which may allow for easier colonisation of H. pylori (66,67) , and may even directly contribute to biliary inflammation (68) .…”