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Background & Aims: Transgenic FVB/N insulin-gastrin (INS-GAS) mice have high circulating gastrin levels, and develop spontaneous atrophic gastritis and gastrointestinal intraepithelial neoplasia (GIN) with 80% prevalence 6 months after Helicobacter pylori infection. GIN is associated with gastric atrophy and achlorhydria, predisposing mice to nonhelicobacter microbiota overgrowth. We determined if germfree INS-GAS mice spontaneously develop GIN and if H pylori accelerates GIN in gnotobiotic INS-GAS mice., Methods: We compared gastric lesions, levels of messenger RNA, serum inflammatory mediators, antibodies, and gastrin among germfree and H pylori-monoinfected INS-GAS mice. Microbiota composition of specific pathogen-free (SPF) INS-GAS mice was quantified by pyrosequencing., Results: Germfree INS-GAS mice had mild hypergastrinemia but did not develop significant gastric lesions until 9 months old and did not develop GIN through 13 months. H pylori monoassociation caused progressive gastritis, epithelial defects, oxyntic atrophy, marked foveolar hyperplasia, dysplasia, and robust serum and tissue proinflammatory immune responses (particularly males) between 5 and 11 months postinfection (P<0.05, compared with germfree controls). Only 2 of 26 female, whereas 8 of 18 male, H pylori-infected INS-GAS mice developed low to high-grade GIN by 11 months postinfection. Stomachs of H pylori-infected SPF male mice had significant reductions in Bacteroidetes and significant increases in Firmicutes., Conclusions: Gastric lesions take 13 months longer to develop in germfree INS-GAS mice than male SPF INS-GAS mice. H pylori monoassociation accelerated gastritis and GIN but caused less severe gastric lesions and delayed onset of GIN compared with H pylori-infected INS-GAS mice with complex gastric microbiota. Changes in gastric microbiota composition might promote GIN in achlorhydric stomachs of SPF mice., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Cancer of the gallbladder is the number one cause of cancer mortality in Chilean women. Incidence rates for this tumor vary widely on a worldwide basis, being approximately 30 times higher in high-risk than in low-risk populations, suggesting that environmental factors such as infectious microorganisms, carcinogens, and nutrition play a role in its pathogenesis. Because several Helicobacter sp. colonize the livers of animals and induce hepatitis, the aim of this study was to determine whether Helicobacter infection was associated with cholecystitis in humans., Methods: Bile or resected gallbladder tissue from 46 Chileans with chronic cholecystitis undergoing cholecystectomy were cultured for Helicobacter sp. and subjected to polymerase chain reaction (PCR) analysis using Helicobacter-specific 16S ribosomal RNA primers., Results: Recovery of Helicobacter sp. from frozen specimens was unsuccessful. However, by PCR analysis, 13 of 23 bile samples and 9 of 23 gallbladder tissues were positive for Helicobacter. Eight of the Helicobacter-specific PCR amplicons were sequenced and subjected to phylogenetic analysis. Five sequences represented strains of H. bilis, two strains of "Flexispira rappini" (ATCC 49317), and one strain of H. pullorum., Conclusions: These data support an association of bile-resistant Helicobacter sp. with gallbladder disease. Further studies are needed to ascertain whether similar Helicobacter sp. play a causative role in the development of gallbladder cancer.

Gastric Helicobacter mustelae was present in 100% of 11 adult female ferrets (Mustela putorius furo). The high immunoglobulin G antibody levels to H. mustelae in all ferrets showed a significant immune response to the organism. Urease mapping of the ferret stomach indicated that the bacteria heavily colonized the proximal duodenum and antrum and, to a lesser extent, the corpus. The histological gastritis observed coincided with presence of H. mustelae. Superficial gastritis was noted in the oxyntic gastric mucosa, whereas in the distal antrum the chronic inflammatory response occupied the full thickness of the mucosa. In the proximal antrum and transitional mucosa, focal glandular atrophy and regeneration were observed. Seven control specific-pathogen-free ferrets were not colonized with the bacteria, did not have detectable levels of immunoglobulin G H. mustelae antibody, and did not have H. mustelae-associated gastritis. The ferret lacks the polymorphonuclear-cell response seen in active chronic gastritis typically described with Helicobacter pylori gastritis in humans. However, the lesion in ferrets does closely resemble the diffuse antral gastritis seen in a subset of adults with H. pylori gastritis as well as children infected with H. pylori. Like H. pylori, H. mustelae adheres tightly to gastric mucosa. The ferret infected with H. mustelae, in addition to specific-pathogen-free uninfected control ferrets, will make longitudinal studies possible, enabling dissection of multiple host and environmental variables that influence the effect of H. mustelae colonization on progression and severity of gastroduodenal disease.

Clostridium difficile is a bacterium that causes antibiotic-associated pseudomembraneous enterocolitis. This bacterium produces a cytotoxin that induces tissue culture assay positivity and an enterotoxin that causes in vivo mucosal injury. In previous studies we have described two altered myoelectric patterns in response to certain diarrheagenic organisms in an in vivo rabbit model. The first pattern was called the migrating action potential complex and is associated with noninvasive agents; the second pattern was called repetitive bursts of action potentials and is characteristic of invasive or cytolytic agents. In this study, we evaluated the effects of purified cytotoxin (2.5-3.75 micrograms) and enterotoxin (140 micrograms) from C. difficile on the myoelectric activity in isolated ileal loops in New Zealand White rabbits. These observations in myoelectric activity were correlated with the results of similar studies by using the crude culture filtrates from C. difficile, or the products of Amicon XM50 filtration of its culture supernatant resulting in a high molecular weight product (0.3 mg protein/ml) and a low molecular weight product (0.57 mg protein/ml). Monopolar silver-silver chloride electrodes were used to record all myoelectric activity for an 8-h period. The animals were then killed, and tissue obtained from the ileal loops was histologically evaluated. Crude culture filtrates of C. difficile induced 7.0 migrating action potential complexes/hour and 6.8 repetitive bursts of action potentials/hour. Saline controls induced no migrating action potential complexes and 0.1 repetitive bursts of action potentials/hour. The high molecular weight filtration product obtained from the culture supernatant of C. difficile induced significantly more repetitive bursts of action potentials (41.1/h) than all agents studied. The purified cytotoxin or enterotoxin induced no migrating action potential complex activity and minimal repetitive bursts of action potential activity (0.9/h and 0.6/h, respectively). These values were not different from the saline controls; however, only the enterotoxin and the high molecular weight filtration product caused mucosal damage. These studies suggest that C. difficile produces a heat-labile substance or substances that alter the motility of the small intestine independent of the proteins responsible for in vivo tissue damage and cytotoxin assay positivity.