Biliary Migration, Colonization, and Pathogenesis of O. viverrini Co-Infected with CagA+ Helicobacter pylori.

Watcharapol Suyapoh,Sirikachorn Tangkawattana,Janina E E Tirnitz-Parker,Banchob Sripa,Sutas Suttiprapa

doi:10.3390/pathogens10091089

Watcharapol Suyapoh, Sirikachorn Tangkawattana + Show 3 more

Open Access

https://doi.org/10.3390/pathogens10091089

Copy DOI

Journal: Pathogens	Publication Date: Aug 26, 2021
Citations: 11	License type: CC BY 4.0

Affiliation: Khon Kaen University, Curtin University

Abstract

Co-infection with the cagA strain of Helicobacter pylori exacerbates the pathology of human liver fluke Opisthorchis viverrini (OV) infection leading to cholangiocarcinoma. However, underlying mechanisms remain unclear. We report a significant increase in cagA-positive and cagA-negative H. pylori in the stomach, blood, bile, and in the OV worms of co-infected Syrian golden hamsters at one hour, three hours, and one month, post-infection, compared to hamsters infected with either OV or H. pylori alone. Except in the worms, H. pylori numbers declined at three months post-infection, particularly in the bile fluid of co-infected animals. Both strains of H. pylori were immunohistochemically detected in the tegument of the worm, as well as in the bile duct epithelium when co-infected with O. viverrine, but not in H. pylori infection alone. Interestingly, only the cagA-positive strain was detected in the gut of the worm. Co-infection between cagA-positive H. pylori and O. viverrini resulted in a more severe biliary pathology and decreased E-cadherin expression in vivo and in vitro than those of the cagA-negative strain. These data suggest that O. viverrini acts as a carrier of cagA-positive H. pylori and co-migrates to the bile ducts, whereas O. viverrini facilitates H. pylori colonization and enhances the biliary pathogenesis and carcinogenesis.

Highlights

Chronic infection of humans with the carcinogenic liver fluke, Opisthorchis viverrini, is a major public health problem in the Lower Mekong region, including Thailand, Lao People’s Democratic Republic, Cambodia, and Southern Vietnam
At 1 month post-infection, cagA-negative H. pylori was detected at significantly higher levels in the gastric mucosa of O. viverrini co-infected hamsters than in animals infected with cagA-positive, or cagA-negative or cagA-positive alone (Figure 2a)
Significantly higher cagA-positive H. pylori copy numbers were observed in the bile fluid samples at 3 months post-infection in the O. viverrini infection group, compared to animals co-infected with cagA-negative, or cagA-positive or cagA-negative H. pylori alone (Figure 2b)

Summary

Introduction

Chronic infection of humans with the carcinogenic liver fluke, Opisthorchis viverrini, is a major public health problem in the Lower Mekong region, including Thailand, Lao People’s Democratic Republic, Cambodia, and Southern Vietnam. Ten million people in these areas are infected with this particular liver fluke [1]. In Thailand, the highest prevalence is reported in the north-eastern part, where about six million people are infected [2,3]. Infection occurs by consuming raw or undercooked freshwater fish containing the infective stage (metacercaria) of the parasite. After ingestion by the host, the metacercaria excyst in the duodenum. Chronic bile duct infection causes several hepatobiliary abnormalities, including biliary periductal fibrosis and the lethal bile duct cancer cholangiocarcinoma (CCA).

Methods

Results

Conclusion