Evaluation of two monkey species (Macaca mulatta and Macaca fascicularis) as possible models for human Helicobacter pylori disease

Abstract

Endoscopic, histologie, and microbiologie evaluations of 21 cynomolgus and 34 rhesus monkeys for naturally occurring Helicobacter pylori infection were done. H. pylori was never isolated from any cynomolgus monkey, but was found in 12 rhesus monkeys. A general correlation existed between a positive culture and a gastric inflammatory response. Inoculation challenges were then undertaken. Four cynomolgus and five rhesus monkeys received two different H. pylori strains isolated from humans. Five rhesus monkeys received an isolate obtained from rhesus monkeys. Evaluation of the cynomolgus monkeys 7 and 14 days later revealed no H. pylori. Endoscopies of the rhesus monkeys were done 7, 14, 21, 28, and 56 days later. One rhesus monkey, which received the isolate from humans, became H. pylori positive at day 21 and remained positive through day 56. Restriction enzyme analysis of genomic DNA at day 56 revealed that the isolate was not identical to the challenge strain isolated from humans. All five rhesus monkeys that received the strain isolated from rhesus monkeys became H. pylori positive by day 14 and remained positive through day 56. Antral inflammation developed in all monkeys. Restriction enzyme analysis of genomic DNA on day 56 confirmed that four of five isolates were identical to the challenge strain isolated from rhesus monkeys. DNA hybridization documented homology between the challenge strains isolated from humans and rhesus monkeys plus those isolated at day 56. In this study, we showed that the rhesus monkey, if given a strain ofH. pylori isolated from rhesus monkeys, develops a gastric infection with accompanying histological changes, making this model suitable for further development.

Helicobacter pylori infection induces duodenitis and superficial duodenal ulcer in mongolian gerbils

“…Experimental models of H pylori infection have been described using gnotobiotic piglets, 3 euthymic germ free mice, 4 athymic nude mice, 5 and monkeys. 6 The Mongolian gerbil also appears to be an appropriate animal model of H pylori infection. [7][8][9] Gastrointestinal diseases such as gastritis, gastric ulcer, and adenocarcinoma that mimic human H pylori infection can be studied in the Mongolian gerbil model.…”

Adhesion of Helicobacter pylori to gastric epithelial cells in primary cultures obtained from stomachs of various animals

“…Several trials were done to establish animal models of H. pylon infection. The infection was successful in monkeys (9) and piglets (8, 22, 24) but unsuccessful in mice and rats (4, 6). These facts correlated well with our present data on H. pylon adhesion to the antral epithelial cells isolated from these anirpals.…”

“…Other attempts were made to clarify the pathogenesis by establishing animal models of H. pylon infection. These studies revealed that, while establishment of H. pylon infection was unsuccessful in germfree rodents such as mice and rats (4,6), the bacteria could colonize the stomachs of monkeys (9), gnotobiotic piglets (8,22,24), gnotobiotic dogs (31), nude mice (21), and Mongolian gerbils (37) when the animals were orally challenged. However, these studies did not reveal why the bacteria colonized the stomachs of some * Corresponding author.…”

Preclinical Assessment of Gastrooesophageal Tolerance of the New Antiosteoporotic Drug Strontium Ranelate: An Endoscopic Study in Monkeys

“…The primate model was described as a good model for human gastroduodenal diseases such as those induced by Helicobacter pylori (Euler et al 1990;Dubois et al 1996). Nevertheless, the ethical limitations linked to the use of primates, the cost to be supported and the difficulties to breed and to handle these species are limitations to carry out extensive investigations.…”