Effects of selective cyclooxygenase-2 inhibitor and non-selective NSAIDs on Helicobacter pylori-induced gastritis in Mongolian gerbils

Background. It is still a point of controversy whether Helicobacter pylori‐infected patients are more likely to develop mucosal damage while taking NSADIs. Selective cyclooxygenase (COX‐2) inhibitors may be associated with less severe gastric mucosal damage than conventional NSAIDs, but this association is undefined in H. pylori‐induced gastritis. The aim of this study was to evaluate the effects of selective COX‐2 and nonselective NSAIDs on H. pylori‐induced gastritis. Methods. After intragastric administration of indomethacin, NS‐398 or vehicle alone, once daily for 5 days in H. pylori‐infected and uninfected Mongolian gerbils, we evaluated gastric mucosal damage, inflammatory cell infiltration and prostaglandin E₂ (PGE₂) concentration. We investigated whether H. pylori infection induced the COX‐2 expression. Results. In H. pylori‐uninfected groups, the indomethacin‐treated group showed the highest mucosal damage score and the lowest PGE₂ concentration. There was no difference in mucosal damage scores and PGE₂ concentration between NS‐398 and vehicle‐alone treated group. In H. pylori‐infected groups, there was no difference in mucosal damage scores, irrespective of the type of drugs administered. The indomethacin‐treated group showed the lowest PGE₂ concentration, similar to that of the NS‐398 and vehicle‐alone treated groups, both without H. pylori infection. Gastric neutrophil and monocyte infiltration scores were higher in H. pylori‐infected groups than in uninfected groups. However, there was no difference in these scores according to the type of drugs administered, within H. pylori‐infected or uninfected groups. COX‐2 protein expression was observed in H. pylori‐infected Mongolian gerbils but not in uninfected ones. Conclusions. Our animal study showed that H. pylori infection induced COX‐2 expression and increased prostaglandin concentration. Administration of NSAIDs decreased the prostaglandin concentration, but did not increase mucosal damage in H. pylori‐induced gastritis. Selective COX‐2 inhibitors, instead of conventional NSIADs, had no beneficial effect on preventing mucosal damage in H. pylori‐induced gastritis.     

Polaprezinc attenuates Helicobacter pylori-associated gastritis in Mongolian gerbils

Background. The ammonia‐monochloramine system plays an important role in Helicobacter pylori‐associated gastric mucosal injury. Polaprezinc, a new antiulcer agent, has a scavenging action against monochloramine. The aim of the experiment was to investigate the inhibitory effects of polaprezinc on the H. pylori‐induced gastritis in Mongolian gerbils. Materials and Methods. Mongolian gerbils fasting for 24 hours were orally given culture broth containing 2–4 × 10⁸ colony‐forming units of H. pylori ATCC 43054 per milliliter. From 4 hours after inoculation until the end of the experiment, gerbils were given chow pellets with or without 0.02% polaprezinc. All gerbils were killed 12 weeks later. The grades of H. pylori density and histologic features of gastritis were evaluated in accordance with the Updated Sydney System. The scavenging effect of polaprezinc on monochloramine was investigated spectrophotometrically. Results. Polaprezinc had little or no influence on the H. pylori density in both pyloric and fundic mucosae. However, it significantly attenuated the development of polymorphonuclear neutrophil activity, mononuclear infiltration, and surface epithelial erosion in both pyloric and fundic mucosae compared with those of the control group. H. pylori inoculation significantly increased the heights of both pyloric and fundic mucosae (mainly due to the increased height of foveolar hyperplasia), but polaprezinc inhibited the increase of mucosal thickness in both pyloric and fundic mucasae. No intestinal metaplasia was detected in this study. Spectrophotometric examination revealed that polaprezinc scavenged monochloramine. Conclusions. Polaprezinc inhibited the development of H. pylori‐induced gastritis through its scavenging action against monochloramine.     

Role of cyclooxygenase-2 functional gene polymorphisms in Helicobacter pylori induced gastritis and gastric atrophy

In India, the role of host genetic factors is poorly studied for Helicobacter pylori associated diseases. Therefore, we evaluated the association of functionally relevant COX-2 gene polymorphisms (-765 G>C and +8473 T>C) in gastritis and precancerous lesions susceptibility. After upper GI endoscopy, 130 rapid urease test positive patients with non-ulcer dyspepsia, also showed positivity for H. pylori using modified Geimsa staining and anti-CagA IgG serology were included. All patients and 260 asymptomatic controls were genotyped for COX-2 variations using PCR-RFLP. COX-2 -765 (GC+CC) genotypes, -765 C allele, +8473 CC genotype, +8473 (TC+CC) genotypes, +8473 C allele, and variant haplotypes imparted high risk for gastritis (P = 0.036, OR = 1.82; P = 0.007, 1.92; P = 0.025, OR = 2.13; P = 0.017, OR = 1.80; P = 0.017, OR = 1.45; P = 0.010, OR = 2.40; P = 0.023, OR = 1.50 and P = 0.012, OR = 2.20 folds, respectively). In contrast, COX-2 -765 C allele carriers had low risk for lymphocyte (P = 0.020, OR = 0.35), plasma cell infiltrations (P = 0.016, OR = 0.33), and gastric atrophy (GA) development (P = 0.019, OR = 0.35). In conclusion, COX-2 variant allele/genotype/haplotype carriers may be at high risk for gastritis. However, COX-2 -765 C allele carriers may be at low risk for GA development.     

Suppression of Helicobacter pylori-induced gastritis by green tea extract in Mongolian gerbils

Since urease of Helicobacter pylori is essential for its colonization, we focused attention on foodstuffs which inhibit the activity of this enzyme. Among plant-derived 77 foodstuff samples tested, some tea and rosemary extracts were found to clearly inhibit H. pylori urease in vitro. In particular, green tea extract (GTE) showed the strongest inhibition of H. pylori urease, with an IC(50) value of 13 microg/ml. Active principles were identified to be catechins, the hydroxyl group of 5(')-position appearing important for urease inhibition. Furthermore, when H. pylori-inoculated Mongolian gerbils were given GTE in drinking water at the concentrations of 500, 1000, and 2000 ppm for 6 weeks, gastritis and the prevalence of H. pylori-infected animals were suppressed in a dose-dependent manner. Since the acquisition by H. pylori of resistance to antibiotics has become a serious problem, tea and tea catechins may be very safe resources to control H. pylori-associated gastroduodenal diseases.     

Enterocromaffin-like cell tumor induced by Helicobacter pylori infection in Mongolian gerbils

Background. Gastric carcinoids are strongly associated with chronic atrophic gastritis A, and it is suggested that hypergastrinemia plays a critical role in development of gastric carcinoids. Since Helicobacter pylori infection causes hypergastrinemia, it is held that H. pylori infection produces gastric carcinoids. We followed the histological changes of H. pylori‐infected stomachs of Mongolian gerbils for a long time. Materials and Methods. Five‐week‐old‐male Mongolian gerbils were infected with H. pylori ATCC 43504 with cagA gene, expressing vacuolating cytotoxin. Determination of the serum gastrin and histopathological examination of the stomach at 6, 12, 18, and 24 months after H. pylori inoculation was studied and compared with uninfected animals . Results In infected animals, the gastric carcinomas appeared 18 and 24 months after infection. Endocrine cell dysplasias and carcinoids with marked atrophic gastritis of the oxyntic mucosa were observed in the infected animals 24 months after H. pylori inoculation. The serum gastrin level in the infected group increased from an average of 86.2 pg/ml at the beginning of the study to an average of 498 pg/ml and 989 pg/ml at 18 and 24 months after infection, respectively. These changes in the serum gastrin levels were significant compared with uninfected controls that showed no changes. Conclusions. H. pylori infection caused not only gastric carcinomas but also enterochromaffin‐like cell tumors in Mongolian gerbils, due to hypergastrinemia. This model is thought to be useful to study the relationship between hypergastrinemia and gastric carcinoids.     

Role of bacterial strain diversity of Helicobacter pylori in gastric carcinogenesis induced by N-methyl-N-nitrosourea in Mongolian gerbils

AIM: Helicobacter pylori is known to enhance gastric carcinogenesis induced by chemical carcinogens. We previously demonstrated that infection with H. pylori strain SS1 did not enhance such carcinogenesis in C57BL/6 mice. Whether this result was due to the bacterial strain SS1 or to the experimental host, C57BL/6 mice, should be addressed. Therefore, we examined whether H. pylori strains introduced to the same host (Mongolian gerbils) differed in carcinogenicity. MATERIALS AND METHODS: H. pylori TN2GF4 strain (CagA(+), VacA(+)) and SS1 strain (CagA functionally(-), VacA(-)) were infected to Mongolian gerbils (n = 126). In the first experiment (induction of gastritis), histologic change in gastric mucosa of gerbils infected by H. pylori (TN2GF4, SS1, vehicle) without N-methyl-N-nitrosourea (MNU) at 1 month or 6 months was assessed. In the second experiment (experimental carcinogenesis), H. pylori (TN2GF4, SS1, vehicle) was inoculated to the gerbils after administration of MNU for 10 weeks, and the number of cancers and histopathologic changes at week 54 were assessed. RESULTS: In the first experiment, activity and inflammation in the TN2GF4 group were significantly greater than in the SS1 group at 1 month, while no significant difference was noted at 6 months. On the other hand, intestinal metaplasia and atrophy were significantly greater with TN2GF4 than with SS1 at 6 months but not at 1 month. In studies on experimental carcinogenesis, microscopically, 47.8% (11/23), 26% (7/26), and 0% (0/26), of animals had gastric adenocarcinoma in the MNU + TN2GF4 group, MNU + SS1 group, and MNU alone group, respectively. CONCLUSION: Both H. pylori strains, TN2GF4 and SS1, promoted carcinogenesis in Mongolian gerbils. The severity of gastritis and destruction and restoration of gastric mucosa may be related to gastric carcinogenesis. That the SS1 strain significantly accelerated carcinogenesis only in Mongolian gerbils and not in C57BL/6 mice suggests the crucial role of host factors in carcinogenesis by H. pylori infection.     

Inhibitory effect of etodolac, a selective cyclooxygenase-2 inhibitor, on stomach carcinogenesis in Helicobacter pylori-infected Mongolian gerbils

The effect of the selective COX-2 inhibitor, etodolac, on Helicobacter pylori (Hp)-associated stomach carcinogenesis was investigated in Mongolian gerbils (MGs). Hp-infected MGs were fed for 23 weeks with drinking water containing 10 ppm N-methyl-N-nitrosourea. They were then switched to distilled water and placed on a diet containing 5-30 mg/kg/day etodolac for 30 weeks. We found that etodolac dose-dependently inhibited the development of gastric cancer, and no cancer was detected at a dose of 30 mg/kg/day. Etodolac did not affect the extent of inflammatory cell infiltration or oxidative DNA damage, but it significantly inhibited mucosal cell proliferation and dose-dependently repressed the development of intestinal metaplasia in the stomachs of Hp-infected MGs. These results suggest that COX-2 is a key molecule in inflammation-mediated stomach carcinogenesis and that chemoprevention of stomach cancer should be possible by controlling COX-2 expression or activity.     

Effects of dexamethasone and FK506 on Helicobacter pylori-induced gastritis and bacterial viability in Mongolian gerbils.

FK506 and dexamethasone were used to investigate whether or not immunosuppression affects H. pylori colonization and gastric mucosal damage induced by Helicobacter pylori in Mongolian gerbils. Two weeks after H. pylori infection, FK506 and dexamethasone or vehicle alone were subcutaneously administered once daily for the following 2 weeks. FK506 or vehicle alone was administered subcutaneously once daily for 5 weeks (1 week before and 4 weeks after infection). In H. pylori-infected animals for 4 weeks, hemorrhagic erosions and inflammatory responses (neutrophil infiltration and lymphoid follicle formation) were induced in gastric mucosa at an incidence of 100%. Both FK506 and dexamethasone administered for 2 weeks markedly reduced such mucosal changes. In these animals, H. pylori viability in the stomach was significantly elevated. FK506 administered for 5 weeks also significantly inhibited the hemorrhagic erosions, edema and neutrophil infiltration in the stomach. H. pylori viability was slightly elevated as compared with the control. It was concluded that the host immune responses might play dual roles both by deteriorating gastritis induced by H. pylori and by protecting against H. pylori infection in its early stage.     

Marked reduction of Helicobacter pylori-induced gastritis by urease inhibitors, acetohydroxamic acid and flurofamide, in Mongolian gerbils.

Urease has been suggested to be essential for colonization and pathogenesis of Helicobacter pylori infection. In the present study, we evaluated the effects of urease inhibitors [acetohydroxamic acid (AHA) and flurofamide (FFA)] on H. pylori-induced gastritis in Mongolian gerbils. Animals were orally inoculated with H. pylori, and given urease inhibitors in their diet throughout the experimental period of six weeks or four weeks, starting from two weeks after H. pylori inoculation. With the administration of AHA at doses of 100, 500, and 2500 ppm throughout the experimental period, H. pylori-induced gastritis in animals was decreased in a dose-dependent manner, significantly so at 2500 ppm. Suppression of gastric lesions was also evident in animals administered 2500 ppm AHA after the H. pylori infection. Bacterial infection rates were reduced to 40-50% of the control value of 100%, by the highest dose of AHA. The potent urease inhibitor, FFA, also caused marked amelioration of H. pylori-associated gastritis on administration at 100 ppm throughout the six-week experimental period or for four weeks after H. pylori infection. Animals treated with FFA had few visible gastric lesions, and the proportion infected with H. pylori was reduced to less than 10%. Since antibiotic-resistant strains of H. pylori have become a serious problem, nonantibiotic urease inhibitors may be very useful to control H. pylori-associated gastroduodenal disease.     

Colonization of Helicobacter pylori in the gastric mucosa of Mongolian gerbils

Helicobacter pylori was orally inoculated into Mongolian gerbils. The organisms were able to colonize in the gastro-mucosal layer of the gerbils, especially in those gerbils which had mucosal lesions caused by indomethacin treatment. The pathological changes developed by H. pylori infection were restricted to the stomachs, and only slightly inflammatory cells were observed.     

Preventive effects of Cladosiphon fucoidan against Helicobacter pylori infection in Mongolian gerbils

Background. Recently, the acquisition by Helicobacter pylori of resistance to antibiotics has become a serious problem. Therefore, nonantibiotic substances are required to diminish H. pylori‐induced gastric lesions. In the present study, the effects of Cladosiphon fucoidan were examined in terms of H. pylori attachment to porcine gastric mucin in vitro and Helicobacter pylori‐induced gastritis in vivo. Methods. The inhibitory effect of Cladosiphon fucoidan and other polysaccharides on H. pylori attachment to porcine gastric mucin was assayed in vitro with mucin‐coated microtiter plates. The effect of Cladosiphon fucoidan on H. pylori‐induced gastritis was examined in vivo using Mongolian gerbils. H. pylori‐inoculated gerbils were given fucoidan in drinking water. Six weeks after H. pylori‐inoculation, gerbils were sacrificed for macroscopic and microscopic examination of gastric lesions and counting of viable H. pylori in the gastric mucosa. Results. Cladosiphon fucoidan inhibited the H. pylori attachment to porcine gastric mucin at pH 2.0 and 4.0. Two other sulfated polysaccharides, Fucus fucoidan and dextran sulfate sodium, also inhibited the attachment but only at pH 2.0. Inhibitory effects of these three sulfated polysaccharides were not observed at pH 7.2 and nonsulfated polysaccharides, such as mannan and dextran, exerted no influence at any pH. In the in vivo experiment, the H. pylori‐induced gastritis and the prevalence of H. pylori infected animals were markedly reduced by fucoidan in a dose‐dependent manner, at doses of 0.05 and 0.5% in the drinking water. Conclusion. Cladosiphon fucoidan may deserve particular attention as a safe agent that can prevent H. pylori infection and reduce the risk of associated gastric cancer.     

Multiple in vivo passages enhance the ability of a clinical Helicobacter pylori isolate to colonize the stomach of Mongolian gerbils and to induce gastritis

The Mongolian gerbil is an excellent animal model for Helicobacter pylori-induced gastritis in humans. In this study, initially low colonization rates of the H. pylori strains ATCC 43504, SS1, or HP87 inoculated into gerbils caused difficulties in establishing this model. In order to increase the colonization ability and pathogenicity, the clinical HP87 isolate was selected for adaptation to the gerbil stomach by multiple in vivo passages through gerbils. Development of gastritis was examined histologically at 4-52 weeks after infection. The proportion of gerbils which tested positive for H. pylori by culture at four weeks after inoculation gradually increased from 11.1% of gerbils inoculated with HP87 without prior in vivo passage (P0) to 100% of gerbils inoculated with HP87 with seven in vivo passages (P7). In addition, adaptation of HP87 resulted in more severe histopathological changes. Gerbils infected with adapted HP87 (P7) exhibited severe infiltration by monomorphonuclear and polymorphonuclear leukocytes in the mucosa, submucosa, and subserosa of the gastric antrum, as well as epithelial changes consisting of hyperplasia, erosion, and ulceration. Histopathological changes increased in severity from four to 52 weeks after infection. Adaptation of HP87 during its passages through gerbils could be due to genetic changes in bacterial colonization factors. Identification of these changes might be useful to understand the underlying mechanism of gastric adaptation and pathogenesis of H. pylori.     

Gastric mucosal changes induced by long term infection with Helicobacter pylori in Mongolian gerbils: effects of bacteria eradication.

Helicobacter pylori infection has been reported to induce various mucosal changes, including gastric adenocarcinoma, in Mongolian gerbils 62 weeks after inoculation. Using Mongolian gerbils, this study examined whether or not eradication of the bacteria with drugs at specified times after infection prevents the development of mucosal changes. After orally inoculating with H. pylori (TN2GF4, vacA- and cagA-positive), the animals were killed 18 months later. Four or 8 months after H. pylori inoculation, eradication was performed by concurrent treatment with omeprazole+clarithromycin. Immediately after treatment ended, in both the 5 and 9 month groups, it was verified that H. pylori was completely eradicated. Autopsy performed 18 months after H. pylori inoculation revealed gastric hyperplastic polyps with erosive lesions and ulcers that were grossly visible in the non-treated control group. In addition, atrophic gastritis, intestinal metaplasia, carcinoids, and adenocarcinomas were histologically observed in the animals. In animals eradicated after 4 months and autopsied after 18 months, however, such mucosal changes were not observed. In contrast, intestinal metaplasia and mucosal atrophy was observed in animals eradicated after 8 months and autopsied after 18 months. It was concluded that early eradication of H. pylori infection with drug therapy can prevent severe gastric mucosal changes, to include adenocarcinomas, in Mongolian gerbils.     

Triple eradication therapy counteracts functional impairment associated with Helicobacter pylori infection in Mongolian gerbils.

Gastric Helicobacter pylori (Hp) infection in Mongolian gerbils is an established experimental model of gastric carcinogenesis resulting from the long-term Hp infection but functional aspects accompanying this Hp-induced progression from gastritis to the cancer, especially changes in gastric acid secretion, gastric blood flow (GBF) and gastrin-somatostatin link have been little studied. It is unclear whether Hp eradication therapy alters the functional and the histopathological changes in this animal model of Hp-infection. We examined the effects of intragastric (i.g.) inoculation of Mongolian gerbils with Hp strain (cagA+ vacA+, 5 x 10(6) CFU/ml) that had been isolated from a patient with gastric ulcer as compared to those induced by vehicle (saline) in gerbils with or without gastric fistula (GF) at 1.2, 4, 6, 9, 12 and 30 wks upon gastric inoculation with this bacteria. An attempt was made to evaluate the influence of anti-Hp triple therapy with omeprazole, amoxicillin and tinidazol on gastric Hp-infection and Hp-induced functional impairment of the gastric mucosa. Gastric mucosal biopsy specimens were taken for the assessment of the morphological changes and the presence of Hp infection using rapid urease test (CLO-test) and the density of Hp-colonization were assessed by counting of the number of bacterial colonies per plate. Gastric blood flow (GBF) was measured by H2-gas clearance technique and the venous blood and the gastric content were collected for the measurement of plasma gastrin levels and the gastric luminal somatostatin level by radioimmunoassay (RIA). The Hp in gastric mucosa was detected in all animals by culture and rapid urease test at various periods upon Hp inoculation. Basal gastric acid in non-infected conscious gerbils with GF reached the level of about 28 +/- 4 micromol/h and this was reduced by over 50% immediately upon the Hp-inoculation and persisted for time intervals tested up to 30 wk. Early lesions were seen 4 wks after the Hp-inoculation and consisted of chronic gastritis with thickened gastric mucosal foldings and elongated interfoveolar ridges. Edema and congestion as well as significant mucosal inflammatory infiltration with lymphoid infiltrate in lamina propria of the mucosa occurred in all infected gerbils. Adenomatous hyperplasia with cellular atypia was observed at 12 wk upon Hp-inoculation together with increased mitotic activity and numerous apoptotic bodies formation, while lamina propria was reduced leaving dilated atypical gastric gland situated "back-to-back". This glandular atypia failed to show lamina propria or submucosa infiltration corresponding to gastric intraepithelial neoplasia. The GBF in Hp-infected gerbils was significantly lower, and a 6-7 fold increase in plasma gastrin levels combined with a significant fall in gastric luminal somatostatin contents observed at all tested periods as compared to vehicle-controls and these effects were counteracted by anti-Hp triple therapy. We conclude that: 1). Hp-infection in Mongolian gerbils in early stages before adenocarcinoma formation results in the development of typical functional and pathological changes such as suppression of gastric secretion and impairment of both, gastric mucosal microcirculation and gastrin-somatostatin link, and 2). this deleterious influence of Hp on gastric morphology and gastric functions is greatly attenuated in gerbils treated with Hp-eradication therapy.     

Effect of lactoferrin on Helicobacter felis induced gastritis.

Lactoferrin possesses antibiotic, antiinflammatory, and immune-modulating properties that may be active against the gastritis-, ulcer- and cancer-inducing bacterium Helicobacter pylori. In vitro testing of bovine and human lactoferrin by several laboratories has shown significant bacteriostatic and bactericidal activity. Subsequent in vivo testing of bovine lactoferrin in animal models of H. pylori infection has shown beneficial effects of this agent. Our laboratory has utilized a mouse model that is infected with the feline strain of this bacterium, H. felis. The resulting gastritis that develops in this model and the effects of bovine lactoferrin and recombinant human lactoferrin (from Aspergillus niger var. awamori, Agennix Inc., Houston, Tex.) treatment were assessed by various measures. Infected animals treated with orally administered lactoferrin showed reversals in all parameters. In addition, when recombinant human lactoferrin was used in combination with low doses of amoxicillin or tetracycline, there was an enhancement in gastritis-reducing activity. Possible mechanisms for these effects of lactoferrin are discussed. Lactoferrin has significant, orally active in vivo actions and should be further investigated for clinical situations involving Helicobacter infections where it may have utility when administered alone and also when given in combination with established antibiotic agents.     

Effects of dexamethasone and FK506 on Helicobacter pylori-induced gastritis and bacterial viability in Mongolian gerbils

FK506 and dexamethasone were used to investigate whether or not immunosuppression affects H. pylori colonization and gastric mucosal damage induced by Helicobacter pylori in Mongolian gerbils. Two weeks after H. pylori infection, FK506 and dexamethasone or vehicle alone were subcutaneously administered once daily for the following 2 weeks. FK506 or vehicle alone was administered subcutaneously once daily for 5 weeks (1 week before and 4 weeks after infection). In H. pylori-infected animals for 4 weeks, hemorrhagic erosions and inflammatory responses (neutrophil infiltration and lymphoid follicle formation) were induced in gastric mucosa at an incidence of 100%. Both FK506 and dexamethasone administered for 2 weeks markedly reduced such mucosal changes. In these animals, H. pylori viability in the stomach was significantly elevated. FK506 administered for 5 weeks also significantly inhibited the hemorrhagic erosions, edema and neutrophil infiltration in the stomach. H. pylori viability was slightly elevated as compared with the control. It was concluded that the host immune responses might play dual roles both by deteriorating gastritis induced by H. pylori and by protecting against H. pylori infection in its early stage.     

Profiling and identification of eubacteria in the stomach of Mongolian gerbils with and without Helicobacter pylori infection

Background. Mongolian gerbils are frequently used to study Helicobacter pylori‐induced gastritis and its consequences. The presence of an indigenous bacterial flora with suppressive effect on H. pylori may cause difficulties with establishing this experimental model. Aim. The aim of the present study was to determine bacterial profiles in the stomach of Mongolian gerbils with and without (controls) H. pylori infection. Methods. Gastric tissue from H. pylori ATCC 43504 and CCUG 17874 infected and control animals were subjected to microbial culturing and histology. In addition, gastric mucosal samples from H. pylori ATCC 43504 infected and control animals were analyzed for bacterial profiling by temporal temperature gradient gel electrophoresis (TTGE), cloning and pyrosequencing of 16S rDNA variable V3 region derived PCR amplicons. Results. Oral administration of H. pylori ATCC 43504, but not CCUG 17874, induced colonization and gastric inflammation in the stomach of Mongolian gerbils. Temporal temperature gradient gel electrophoresis (TTGE) and partial 16S rDNA pyrosequencing revealed the presence of DNA representing a mixed bacterial flora in the stomach of both H. pylori ATCC 43504 infected and control animals. In both cases, lactobacilli appeared to be dominant. Conclusion. These findings suggest that indigenous bacteria, particularly lactobacilli, may have an impact on the colonization and growth of H. pylori strains in the stomach of Mongolian gerbils.     

幽门螺杆菌感染蒙古沙鼠胃部菌群改变及病理学变化

目的观察蒙古沙鼠感染幽门螺杆菌（Helicobacter pylori,H.pylori）后胃部菌群及病理学变化。方法 5周龄蒙古沙鼠60只,随机分为实验组（30只）和对照组（30只）。所有沙鼠禁食不禁水24 h后,实验组灌喂109CFU/mLH.pylori菌液0.5 mL/只,连续3次。对照组灌喂无菌肉汤。在4、8、16、24和48周处死动物,进行胃部菌群分析和H.pylori分离培养及病理学检查。结果正常沙鼠胃中存在着以乳酸菌为主的正常菌群[（8.43±5.21）×105CFU/g],感染H.pylori后正常菌群数量显著减少;实验组沙鼠H.pylori感染率为100%,第4周可见沙鼠胃组织红肿充血,第8周有炎性细胞浸润,16周和24周出现糜烂,48周见出血、慢性活动性胃炎及溃疡。对照组沙鼠无H.pylori定植及组织学病变。结论 H.pylori感染使蒙古沙鼠胃内正常菌群发生变化,从而引起胃炎和胃溃疡发生。     

Genetic consequences of group living in Mongolian gerbils

Social behavior can shape the local population genetic structure of mammals. Group living can increase pairwise genetic relatedness of mammals at a local level but differentiate the genetic structure at a population level through offspring philopatry and nonrandom mating. Our study aimed to test the hypothesis that social groups of Mongolian gerbils (Meriones unguiculatus) would consist of genetically related individuals due to offspring philopatry and would have distinct genetic structures because of restricted gene flow among social groups and nonrandom mating. We genotyped 327 wild gerbils, live captured from 28 social groups in Inner Mongolia, China, using nine microsatellite loci. The within-group pairwise genetic relatedness coefficient averaged 0.28 ± 0.14 (standard deviation), whereas the average pairwise genetic relatedness coefficient of the whole gerbil population was 0.0 ± 0.2. Additionally, the value of the global F statistic (F(st)) was 0.21, suggesting a substantial genetic differentiation among social groups of Mongolian gerbils. The Bayesian clustering divided the 327 gerbils into 23 distinct genetic clusters. Therefore, our results show that high within-group genetic relatedness and among-group genetic differentiation are the genetic consequences of group living in social mammals because of restricted gene flow, female philopatry, and nonrandom mating within social groups.