Male Syrian Hamsters Experimentally Infected with Helicobacter spp. of the H. bilis Cluster Develop MALT‐Associated Gastrointestinal Lymphomas

Abstract

Background Aged hamsters naturally infected with novel Helicobacter spp. classified in the H. bilis cluster develop hepatobiliary lesions and typhlocolitis. Methods To determine if enterohepatic H. spp. contribute to disease, Helicobacter-free hamsters were experimentally infected with H. spp. after suppression of intestinal bacteria by tetracycline treatment of dams and pups. After antibiotic withdrawal, weanlings were gavaged with 4 H. bilis-like Helicobacter spp. isolated from hamsters or H. bilis ATCC 43879 isolated from human feces, and compared to controls (n = 7 per group). Results H. bilis 43879 dosed hamsters were necropsied at 33 WPI due to lack of detectable infection by fecal PCR; at necropsy, 5/7 were weakly PCR positive but lacked intestinal lesions. The remaining hamsters were maintained for ~95 WPI; chronic H. spp. infection in hamsters (6/7) was confirmed by PCR, bacterial culture, FISH and ELISA. Hamsters had mild to moderate typhlitis, and three of the male H. spp. infected hamsters developed small intestinal lymphoma, in contrast to one control. Of the three lymphomas in H. spp. infected hamsters, one was a focal ileal MALT B cell lymphoma, while the other two were multicentric small intestinal large B cell lymphomas involving both the MALT and extra-MALT mucosal sites with lymphoepithelial lesions. The lymphoma in the control hamster was a diffuse small intestinal lymphoma with a mixed population of T and B cells. Conclusions Results suggest persistent H. spp. infection may augment risk for gastrointestinal MALT origin lymphomas. This model is consistent with H. pylori/heilmannii associated MALT lymphoma in humans and could be further utilized to investigate mechanisms of intestinal lymphoma development.

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

“…Hamsters have been found naturally infected in various tissues with several novel Helicobacter spp. (21)(22)(23)(24) belonging to the H. bilis cluster, which is known to be involved in hepatobiliary lesions (21,25). To support this, H. bilis could be detected in 14.9 and 9.4% of patients with CCA and cholelithiasis, respectively, and was absent from the control group (10).…”

Other Helicobacters and gastric microbiota

“…After 2 years of infection, all hamsters showed chronic typhlitis, whereas three developed intestinal lymphomas. Therefore, Woods et al . suggested a higher risk for the development of MALT lymphomas when Helicobacter infections become persistent.…”

Syrian Hamsters as a Small Animal Model for Emerging Infectious Diseases: Advances in Immunologic Methods

“…It has been used to examine the course of disease in many infectious disease models including Andes virus, Sin Nombre virus, Chikungunya virus, Nipah virus, and Ebola virus DeBuysscher et al 2013;Ebihara et al 2012;Safronetz et al 2011b;Bosco-Lauth et al 2015). It is also useful in non-infectious disease models in hamsters such as cancer and encephalopathic diseases (Woods et al 2015;Clouse et al 2015;Elder et al 2013). While the use of this technique in hamsters is typically limited to examining preserved tissues that display disease pathology, the advantages are that cross sections of entire tissues can be visualized to give a more representative image of disease tropism and the presence of immune cells or of particular pathogens can easily be detected (Schacht and Kern 2015).…”

“…In recent years, transcriptome sequencing and analysis has been utilized to provide sets of mRNA that are expressed in a given species, help provide insights into the expression profiles of these species, and for the development of microarrays for the detection of gene expression (Tchitchek et al 2014;Ying et al 2015). The description of the transcriptome of mice, rats, and humans has been critical for the increasing use of microarray for examining expression profiles in tissues in many models (Yu et al 2009;Okazaki et al 2002;Yang et al 2010;Maywood et al 2009). Recently, hamster transcriptome sequencing and analysis has been performed in several models Yu et al 2009;Yang et al 2010;Maywood et al 2009;Hohlweg et al 2003;Schmucki et al 2013).…”

“…These advantages are why many consider hamsters a superior alternative to other small animals for use in research. For the development of vaccines and therapeutic approaches, some consider hamsters a higher standard as small animal model than mice and as such hamsters have been utilized in a wide range of models, from those examining diabetes, atherosclerosis, neural plasticity, to cancer (Table 1) (Bhathena et al 2011;Dillard et al 2010;Jové et al 2013;Staffend and Meisel 2012;Woods et al 2015;Vijayalingam et al 2014). However, the use of hamsters for models of pathogenic human diseases may be the most valuable due to comparable disease progression seen in hamsters to that of humans for many infectious diseases including bacteria, viruses, and parasites (Dondji et al 2008; da Silva-Couto et al 2015;Kuehne et al 2014;Safronetz et al 2012).…”