Prevention of Helicobacter pylori infection by lactobacilli in a gnotobiotic murine model.

BACKGROUND: Helicobacter pylori is a bacterium which causes gastric inflammatory diseases. Oral inoculation of H pylori usually results in only a temporary colonisation without a successful infection in the stomach of conventional mice in which lactobacilli are the predominant indigenous bacteria. AIM: To determine whether lactobacilli exert an inhibitory effect on colonisation by H pylori in the stomach. METHODS: The effects of H pylori on attachment to murine and human gastric epithelial cells and the H pylori mediated release of interleukin-8 (IL-8) by these cells were examined in vitro. Lactobacillus salivarius infected gnotobiotic BALB/c mice and control germ free mice were inoculated orally with H pylori to examine whether L salivarius can inhibit colonisation by H pylori. RESULTS: L salivarius inhibited both the attachment and IL-8 release in vitro. H pylori could not colonise the stomach of L salivarius infected gnotobiotic BALB/c mice, but colonised in large numbers and subsequently caused active gastritis in germ free mice. In addition, L salivarius given after H pylori implantation could eliminate colonisation by H pylori. CONCLUSION: These findings suggest the possibility of lactobacilli being used as probiotic agents against H pylori.     

The therapeutic effect of bovine lactoferrin in the host infected with Helicobacter pylori

BACKGROUND: It remains unclarified whether bovine lactoferrin (bLF) can exert a therapeutic effect on the host infected with Helicobacter pylori. METHODS: Germfree BALB/c mice were orally inoculated with H. pylori to induce infection. Three weeks after infection the mice were given bLF orally once daily for 2 or 4 weeks and were then killed to examine the bacterial number in the stomach and the serum antibody titer to H. pylori. To count the number of epithelium-bound H. pylori, the resected stomach was agitated in phosphate-buffered saline to remove non-bound H. pylori before bacterial enumeration. RESULTS: The administration of 10 mg bLF for 3 to 4 weeks decreased the number of H. pylori in the stomach to one-tenth and also exerted a significant inhibitory effect on the attachment of H. pylori to the stomach. As a result, the serum antibody titer to H. pylori, whose level is presumed to represent the size of the immune response by the host, thereby reflecting the degree of bacterial attack, decreased to an undetectable level. CONCLUSIONS: These findings suggest that bLF exerts an inhibitory effect on colonizing H. pylori by detaching the bacterium from the gastric epithelium and by exerting a direct anti-bacterial effect.     

幽门螺杆菌疫苗接种小鼠产生免疫后胃炎的影响因素

目的:研究幽门螺杆菌(H pylorl)疫苗接种小鼠产生免疫后胃炎的影响因素．方法:将H pylori疫苗免疫C57BL／6和BALB／c的小鼠,观察攻击后胃黏膜H pylori定植和炎症情况．将H pylori疫苗免疫C57BL／6小鼠,然后予不同菌量的H pylori攻击,观察胃黏膜H Pylori定植和炎症情况．将H pylori疫苗经口和经腹腔免疫C57BL／6小鼠,观察攻击后胃黏膜H pylori定植和炎症情况.对感染H pylori的C57BL／6小鼠予H pylori疫苗治疗,观察治疗免疫后胃黏膜H pylori定植和炎症情况．结果:不同品系的小鼠免疫保护程度无明显差异,但C57BL／6小鼠免疫后胃炎重于BALB／c小鼠．接受不同攻击茵量的小鼠保护程度无明显差异,但大的攻击茵量可诱导更严重的免疫后炎症．不同免疫途径诱导的免疫保护程度及攻击后不同时间点的炎症程度均无显著性差异．治疗性免疫导致H pylori定植明显降低,同时也引发更为严重的胃炎．结论:在不同的免疫宿主、免疫途径和治疗性免疫中均存在免疫后胃炎．免疫后胃炎的强弱程度受免疫宿主和攻击菌量的影响．     

Comparative Analysis of Colonization of Helicobacter pylori and Glycolipids Receptor Density in Mongolian Gerbils and Mice

The Mongolian gerbil has been used as an excellent experimental animal model for studying Helicobacter pylori infection because it can stably colonize and induce severe chronic gastritis, ulceration, and cancer-simulating human diseases in this animal. In contrast, H. pylori can only induce mild inflammation in many mouse models. The aim in this study is to clarify the difference of induction of pathological lesions in the two animal models. SPF ICR mice and Mongolian gerbils were inoculated with a clinically isolated strain of H. pylori. Six weeks after inoculation, bacteria colonizing the stomach were counted. Immunohistochemical staining and biochemical analyses of three putative receptor glycolipids were performed with monoclonal antibodies to the respective glycolipids. Significantly higher numbers of H. pylori were recovered from the stomachs of Mongolian gerbils than mice (5.77 ± 0.46 log CFU vs 4.17 ± 0.55 log CFU, P < 0.01). Immunohistochemical studies showed that sulfatide expression in the gastric mucosa of Mongolian gerbils was much stronger than that in mice, whereas the expression of Lewis^b glycolipid and GM3 were almost equal. Quantitative analysis of each glycolipid by thin-layer chromatography confirmed the results of immunohistochemical study, showing 4.1 times higher sulfatide content in the Mongolian gerbil stomach. The content of both Lewis^b and GM3 was almost equivalent in these two animals. In conclusions, higher levels of sulfatide expression, a putative adhesion receptor, in the gastric mucosa of Mongolian gerbils may allow abundant colonization by H. pylori, resulting in the development of gastric lesions in this animal model.     

幽门螺杆菌感染BALB/c小鼠模型的研究

目的　建立稳定的Hp感染BALB/c小鼠模型 ,用于Hp致病、免疫和防治的研究。 方法　选用临床分离株 ,应用外科手术法向小鼠胃内直接接种Hp菌液 0 2ml(10 9CFU/ml) ;接种后不同时间取小鼠胃粘膜组织进行细菌学和病理学检查。结果　接种后 2～ 8周 ,小鼠胃内均可分离到Hp ,Hp分离阳性率为 95 %。病理学检查显示鼠胃粘膜明显炎症。感染鼠用阿莫西林治疗后 ,鼠胃组织Hp培养均转阴性。结论　使用Hp鼠胃接种法 ,能建立稳定的Hp感染BALB/c小鼠模型     

Protective anti-Helicobacter immunity is induced with aluminum hydroxide or complete Freund's adjuvant by systemic immunization.

To determine whether systemic immunization against Helicobacter pylori could be achieved with an adjuvant approved for human use, the efficacy of vaccination with Helicobacter antigen in combination with aluminum hydroxide (AlOH) was evaluated in a murine model of Helicobacter infection. Immunization with antigen and AlOH induced interleukin-5-secreting, antigen-specific T cells, and immunization with antigen and complete Freund's adjuvant induced interferon-gamma-secreting, antigen-specific T cells, as determined by ELISPOT assay. Both immune responses conferred protection after challenge with either H. pylori or H. felis, as confirmed by the complete absence of any bacteria, as assessed by both histology and culture of gastric biopsy samples. Protection was antibody independent, as demonstrated with antibody-deficient muMT mice (immunoglobulin-gene knockout mice), and CD4(+) spleen T cells from immunized mice were sufficient to transfer protective immunity to otherwise immunodeficient rag1(-/-) recipients. These results suggest an alternative and potentially more expeditious strategy for development of a human-use H. pylori vaccine.     

Intragastric nitric oxide/nitrite in Helicobacter pylori-infected subjects

BACKGROUND: Nitrite (NO2-) in swallowed saliva is reduced to nitric oxide (NO) and other nitrogen oxides by the intragastric acidity. This mechanism is probably important for the intragastric clearance of ingested micro-organisms and nitrosating compounds. The study examines the balance between intragastric NO and NO2- in relation to endogenous acid production and infection with Helicobacter pylori. METHODS: Six healthy H. pylori-negative and six H. pylori-positive volunteers with no known gastroduodenal pathology were examined after an overnight fast. Gastric NO was measured using a chemiluminescence technique and pH as well as NO2- were analysed in gastric aspirates. RESULTS: Gastric NO was slightly lower in H. pylori-positive subjects (1560 +/- 211 ppb) than in uninfected controls (2112 +/- 430 ppb; P > 0.05) during basal conditions, whereas both pH and NO2- concentration were similar in the two groups. During inhibition of acid secretion (omeprazole 20 mg b.i.d. over 5 days) median pH and mean NO2- concentration in gastric aspirates were significantly higher in H. pylori positives than in the controls. Furthermore, during omeprazole treatment the intragastric NO levels were almost absent in H. pylori positives, whereas approximately 50% remained in H. pylori-negative individuals. CONCLUSION: Proton-pump inhibition in H. pylori-infected individuals abolishes the intragastric chemical reduction of swallowed NO2- in the fasting stomach.     

Establishment of a Small Animal Model for Human Helicobacter pylori Infection Using Germ-Free Mouse

Objective : To understand why oral inoculation of Helicobacter pylori resulted in continuous colonization of the stomach in germ-free athymic mice, but only temporary colonization in mice that were not germ-free. Methods : We inoculated germ-free and "not-germ-free" euthymic mice with H. pylori and studied the resulting colonization of the stomach, comparing it against the germ-free athymic mouse model. In addition, we inves-tigated Lactobacillus in the above-described three mouse groups. Results : H. pylori were detected in all germ-free athymic mice and all germ-free euthymic mice continuously. However, in all euthymic mice that were not germ-free, H. pylori was detected only tem-porarily after inoculation. Lactobacilli were detected only in the not-germ-free mouse group. The number of H. pylori in the germ-free euthymic mice was signifi-cantly lower than in the germ-free athymic mice during the period of this study after inoculation. Conclusions : We therefore suggest that the growth of H. pylori may be suppressed by the immunological sytem and eradi-cated by Lactobacilli previously inhabiting the stomach.     

Functional and morphological aspects of Helicobacter pylori-induced gastric cancer in Mongolian gerbils

BACKGROUND: Helicobacter pylori infection of Mongolian gerbils is an established model of gastric carcinogenesis, but gastric secretory aspects of this carcinogenesis have not been studied. METHODS: The effects of single intragastric inoculation of gerbils with H. pylori strain (cagA+ vacA+, 5 x 10(6) CFU/ml) or vehicle (saline) were examined at 1, 2, 4, 6, 9, 12 and 30 weeks from inoculation. Gastric morphology, the presence of H. pylori using the rapid urease test, the density of H. pylori and 16S rRNA and the plasma gastrin and somatostatin were determined. RESULTS: H. pylori was detected in gastric mucosa in all infected animals. Basal gastric acid in gerbils was reduced by about 50% after H. pylori inoculation. Early lesions seen at 4 weeks after H. pylori inoculation consisted of chronic gastritis with thickened mucosal folds, oedema, congestion and mucosal lymphocytic infiltration. Adenomatous hyperplasia with cellular atypia with increased mitotic activity and the formation of apoptotic bodies and visible erosions and ulcerations were observed at 12-30 weeks after inoculation. The atypical gastric glands were situated 'back-to-back', suggesting gastric pre-cancer. The gastric blood flow in H. pylori-infected gerbils was significantly lower than that in the controls. Six- to seven-fold increase in plasma gastrin levels combined with significant fall in gastric somatostatin contents and the intraepithelial neoplasia were noticed in gerbils at all tested periods. CONCLUSION: H. pylori-infection in gerbils resulted in gastric pre-cancer associated with functional changes, such as suppression of gastric secretion and impairment of both gastric mucosal microcirculation and the gastrin-somatostatin link.     

Enhanced plasma ghrelin levels in Helicobacterpylori-colonized,intedeukin-1-receptor type 1-homozygous knockout （IL-1R1^-/-） mice

AIM: Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor, and it plays a role in stimulating the growth hormone secretion, food intake, body weight gain and gastric motility. Eradication of Helicobacter pylori (H pylori) was shown to be associated with increase of the body weight. On the other hand, H pylori infection evokes the release of gastric IL-1beta. The present study was designed to investigate the involvement of the gastric IL-1 signal in the ghrelin dynamics in H pylori-colonized mice. METHODS: Twelve-week-old female IL-1-receptor type 1-homozygous-knockout mice (IL-1R1(-/-)) and their wild-type littermates (WT) were orally inoculated with H pylori (Hp group), while other cohorts received oral inoculation of culture medium (Cont group). Thirteen weeks after the inoculation, the mice were examined. The plasma and stomach ghrelin levels and the gastric preproghrelin mRNA were measured. RESULTS: Although the WT mice with H pylori infection showed a significantly decreased body weight as compared with that of the animals without H pylori infection, H pylori infection did not influence the body weight of the IL-1R1-knockout (IL-1R1(-/-)) mice. In the H pylori-infected IL-1R1(-/-) mice, the total and active ghrelin levels in the plasma were significantly increased, and the gastric ghrelin level was decreased. No significant differences were noted in the gastric preproghrelin mRNA expression. CONCLUSION: Ghrelin secretion triggered by H pylori infection might be suppressed by IL-1beta, the release of which is also induced by the infection, resulting in the body weight loss of mice with H pylori infection.     

The role of gastric acid in the H. pylori-induced gastritis in mouse]

BACKGROUND/AIMS: This study was designed to investigate the role of gastric acid in the extent of H. pylori-induced gastritis. METHODS: Twenty eight mice were inoculated with live H. pylori. They were allocated into four groups. Mice in group I received no treatment, group II mice were treated with sham injection, group III received 125 microg/kg body weight of pentagastrin, while group IV received 250 microg/kg body weight of pentagastrin subcutaneously three times a week. After 7 months, the mucosal pH, H. pylori density, neutrophils and monocytes infiltration, and the degree of atrophy were assessed in the stomach. RESULTS: In the gastric body, the densities of H. pylori were not different among groups. The degree of neutrophil infiltration was significantly lower in group IV compared to other groups (p<0.05). The degree of monocyte infiltration was also significantly lower in group IV than group III (p<0.05). In the gastric antrum, there was no significant difference of the H. pylori density, neutrophil and monocyte infiltration, and degree of atrophy among the groups. The mice with the gastric mucosal pH lower than mean of 3.2 had significant lower level of H. pylori density (1.4 vs. 2.4, p=0.04), and infiltration of neutrophils (0.9 vs. 2.3, p=0.018), and monocytes (1.2 vs. 1.8; p=0.011) than the those with mucosal pH above 3.2 in the body of stomach. CONCLUSIONS: Gastric acid plays a role in suppressing the proximal propagation of H. pylori-induced gastritis to the body of stomach.     

Evaluation of New Therapy for Eradication of H. pylori Infection in Nude Mouse Model

Objectives: developing a new therapy for eradication of H. pylori by using the nude mouse mode). Methods: By quantifying the number of colonies of Helicobacter pylori and the score of H. pylori -associated gastritis from the gastric tissue following different drug regimens in inoculated nude mice, we evaluated the effectiveness of each regimen, including a new drug, plaunotol. Drugs were administered daily for a 1-wk period, beginning 4 wk after inoculation. Results: In the examination after therapy, the number of colonies of H. pylori and the score of gastritis in the triple-therapy group were significantly lower than in any of the singlely- and dual-drug groups or control group from 5 wk to the end of the study after inoculation. Inflammation of the stomach was less apparent in the treatment groups than in the control group. Conclusion: With the nude mouse model, we quantitatively demonstrated that the new triple therapy is the most effective therapy for eradication of H. pylori.     

Concomitant alterations in intragastric pH and ascorbic acid concentration in patients with Helicobacter pylori gastritis and associated iron deficiency anaemia

BACKGROUND: Seroepidemiological and clinical studies suggest that Helicobacter pylori may cause iron deficiency anaemia (IDA) in the absence of peptic lesions by undefined mechanisms, which still remain to be fully elucidated. Gastric acidity and ascorbic acid (AA) promote iron absorption. AA is lowered in the presence of H pylori infection. H pylori can cause atrophic body gastritis with achlorhydria, decreased iron absorption, and consequent IDA. Whether alterations in intragastric acidity and AA concentrations play a role in IDA developing in patients with H pylori gastritis remains to be determined. Aim: To evaluate gastric juice pH and gastric juice and plasma AA in patients with H pylori infection and unexplained IDA, compared with controls with IDA and a healthy stomach or with controls with H pylori infection and no IDA. RESULTS: Patients with IDA and H pylori gastritis were characterised by concomitant increased intragastric pH (median value 7) and decreased intragastric AA (median value 4.4 micro g/ml) compared with controls with a healthy stomach (median pH 2; median intragastric AA 17.5 micro g/ml) and with H pylori positive controls without IDA (median pH 2.1; median intragastric AA 7.06 micro g/ml). Intragastric AA was inversely related to pH (r=-0.40, p=0.0059) and corporal degree of gastritis (r=-0.53, p=0.0039). Plasma AA concentrations were lower in all infected groups than in healthy controls. CONCLUSIONS: Patients with unexplained IDA and H pylori gastritis present concomitant changes in intragastric pH and AA that may justify impaired alimentary iron absorption and consequent IDA.     

Virulence of water-induced coccoid Helicobacter pylori and its experimental infection in mice

AIM: To explore the virulence and the infectivity of coccoid Helicobacter ppylori(H.pylori) transformed from spiral form by exposure to sterile tap water.METHODS: Three strains of H.pylori, isolated from gastric biopsy specimens of confirmed peptic ulcer, were converted from spiral into coccoid form by exposure to sterile tap water.Both spiral and coccoid forms of H.pylori were tested for the urease activity, and the adherence to Hep-2 cells. The presence of flagella was examined under electron microscopy. In the experimental animal infection, the spiral and coccoid forms of H.pylori originated from the same strain F49 were inoculated intragastrically into BALB/c mice respectively four times at a 3-day interval. Half of the mice from each group were sacrificed at Day 21 and Day 28 after the last inoculation. Histology and H.pylori colonization were detected by urease test of gastric mucosa, cultures of H. pylori,and electron microscopy and so on.RESULTS: The urease activity and the ability of adherence to Hep-2 cells were found to be lower in coccoid H.pylori than that in its spiral form. For example, the transformation in strain F44 led to a significant decrease of the adherence rate and adherence index from 70.0±5.3 % to 30.2±3.5 %(P＜0.01), and from 2.6±0.4 to 0.86±0.3 (P＜0.01),respectively. The flagella of coccoid H.pylori were observed under electron microscope. In the experimental infection in mice, the positive rate of gastric mucosa urease test was 93.8 % (15/16) in the group infected by spiral H.pylori and 50 % (8/16) in the group infected by coccoid H. pylori,and the estimated coccoid H.pylori colony number was 1.75 vs0,56. The positive rates of H. pyloriculture were 87.5 %(14/16) in spiral H. pylori group and 68.8 % (11/16) in coccoid H.pylorigroup. There was no significant difference in either urease test or bacterial culture rate between the groups examined at Day 21 and Day 28 after inoculation. Electron microscopic examination of the samples taken from both groups showed the adherence of H. pylori in spiral,bacillary and coccoid shapes to the epithelial cells of gastric wall. Histological examination showed the occurrence of gastric mucosal injury as indicated by various degrees of erosion, ulcer, and inflammatory cell infiltration. Mucosal injury was slighter in the mice infected by coccoid H. pylori.No positive result was obtained in the control group that received intragastrical administration of sterile tap water.     

Role of Helicobacter pylori infection on neuronal expression in the stomach and spinal cord of a murine model

OBJECTIVE: To investigate the effect of Helicobactor pylori (H. pylori) infection on neuronal expressions in the stomach and spinal cord of mice so as to explain dyspepsia symptoms in H. pylori infected patients. METHODS: C57BL/6 female mice were studied at 2 weeks (acute infection group) and 12 weeks (chronic infection group) after H. pylori inoculation. Histological analyses for gastric inflammation and bacterial colonization were assessed by HE staining and Warthin–Starry staining. Fos, vasoactive intestinal polypeptide (VIP) and calcitonin gene‐related peptide expressions (CGRP) were studied by immunohistochemistry. RESULTS: H. pylori colonization was present mainly in pyloric region, but bacterial density was similar in both infected groups. The intensity of mucosal inflammation and activity was significantly higher in two infected groups than in those in the control group. The degree of mononuclear and polymorphonuclear cell infiltration in proventricular‐glandular region and gastric corpus at 12 weeks after H. pylori inoculation was higher than that at 2 weeks after inoculation. The neuronal expressions of fos, VIP, and CGRP in the stomach and spinal cord were significantly more marked in the infected groups than in the control group, but there was no significant difference between two infected groups. CONCLUSION: H. pylori infection induced different degrees of gastric mucosal inflammation in the murine model. Both early and chronic infection groups of mice showed enhanced neuronal expressions of fos, VIP and CGRP of stomach and spinal cord and these could form a basis for appearance of functional dyspeptic symptoms in patients with H. pylori infection.     

Pathogenicty and immune prophylaxis of cag pathogenicity island gene knockout homogenic mutants

AIM: To clarify the role of cag pathogenicity island (cagPAI) of Helicobacter pylori (H pylori ) in the pathogenicity and immune prophylaxis of H pylori infection. METHODS: Three pairs of H pylori including 3 strains of cagPAI positive wildtype bacteria and their cagPAI knockout homogenic mutants were utilized. H pylori binding to the gastric epithelial cells was analyzed by flow cytometry assays. Apoptosis of gastric epithelial cells induced by H pylori was determined by ELISA assay. Prophylaxis effect of the wildtype and mutant strains was compared by immunization with the sonicate of the bacteria into mice model. RESULTS: No difference was found in the apoptasis between cagPAI positive and knockout H pylori strains in respective of the ability in the binding to gastric epithelial cells as well as the induction of apoptosis. Both types of the bacteria were able to protect the mice from the infection of H pylori after immunization, with no difference between them regarding to the protection rate as well as the stimulation of the proliferation of splenocytes of the mice. CONCLUSION: The role of cagPAI in the pathogenicity and prophylaxis of H pylori infection remains to be cleared.     

A small animal model of human Helicobacter pylori active chronic gastritis

Isolation of a spiral-shaped bacterium closely related to Helicobacter pylori from the cat stomach made it possible to investigate new small animal models of gastric infection. Pure cultures of this bacterium, provisionally named "Helicobacter felis," were fed to germ-free mice. The organism colonized the stomach in large numbers in mucus and deep in the gastric pits and showed the same gastric trophism found with H. pylori. Significant histopathology was seen in all H. felis-infected mice. At 2 weeks postinfection, an acute inflammatory response was seen composed primarily of eosinophils and neutrophils. At 3 weeks, the polymorphonuclear response was more pronounced with large numbers of neutrophils in some areas forming small microabscesses. Lymphocytes also increased in number. By 8 weeks, several relatively large lymphoid nodules were present in the submucosa. Multiple small microabscesses were still present in the pyloric mucosa. This is the first animal model of bacterial gastritis to be described that shows progression from acute inflammation to persistent acute on chronic inflammation (active chronic) as is seen in human infection with H. pylori.     

Rapid elimination of Helicobacter pylori and reduction of histocompatibility leucocyte antigen-DR expression 12 h after a single dose of omeprazole, amoxycillin and metronidazole triple therapy

BACKGROUND: Studies of eradication of Helicobacter pylori and subsequent resolution of H. pylori-related gastritis, have focused mainly on medium and long-term change following eradication therapies. Results from those studies have shown that both acute and chronic inflammatory changes found in gastric mucosa eventually return to normal. However, the early events in the stomach, particularly the effects on bacterial density and acute inflammatory markers of anti-H. pylori treatment, are largely unknown. The objective of this study was therefore to examine changes in the number of H. pylori, and the severity of gastric mucosal inflammation in the gastric biopsy specimens of patients before (0 h group, n = 14) and 12 h (12 h group, n = 14) after initiating anti-H. pylori treatment. METHODS: Biopsies were assessed, either quantitatively or semi-quantitatively, for the presence of H. pylori, neutrophils, mast cells, intraepithelial lymphocytes and the expression of histocompatibility leucocyte antigen (HLA)-DR by gastric epithelium and the results were compared between groups. RESULTS: Median H. pylori scores were 5 (range 2-5) and 0 (range 0-2) in biopsies from untreated and 12 h post-treatment groups, respectively (P < 0.001). In most 12 h post-treatment biopsies, H. pylori organisms could not be identified. There was a significant reduction in HLA-DR expression by gastric epithelium (median 3.5 with range 2-4 at 0 h group vs median 2 with range 0-4, P < 0.05), but there was no significant difference in the number of intraepithelial lymphocytes, CD3+ cells, mast cells or the distribution and density of neutrophils (all P > 0.05). Furthermore, the severity of gastritis as scored with the Sydney system was similar in both untreated and treated groups. CONCLUSIONS: The results of this study indicate that elimination of H. pylori organisms and resolution of some inflammatory markers occurs as early as 12 h following a single dose of omeprazole 40 mg, amoxycillin 1.0 g and metronidazole 400 mg, which suggests that rational therapeutic strategies with shorter duration using the currently available drugs may be possible.     

Helicobacter Infection and Gastric Ethanol Metabolism

The organism frequently colonizing the stomach of patients suffering from chronic active gastritis and peptic ulcer disease– Helicobacter pylori –possesses marked alcohol dehydrogenase (ADH) activity. Consequently, Helicobacter infection may contribute to the capacity of the stomach to metabolize ethanol and lead to increased acetaldehyde production. To study this hypothesis, we first determined ADH activity in a variety of H. pylori strains originally isolated from human gastric mucosal biopsies. ADH activity was also measured in endoscopic gastric mucosal specimens obtained from H. pylori -positive and -negative patients. Furthermore, we used a mouse model of Helicobacter infection to determine whether infected animals exhibit more gastric ethanol metabolism than noninfected controls.
Most of the 32 H. pylori strains studied possessed clear ADH activity and produced acetaldehyde. In humans, gastric ADH activity of corpus mucosa did not differ between H. pylori -positive and -negative subjects, whereas in antral biopsies ADH activity was significantly lower in infected patients. In mice, gastric ADH activity was similar or even lower in infected animals than in controls, depending on the duration of infection, despite the fact that the infectious agent used– Helicobacter felis –showed ADH activity in vitro. In accordance with this, Helicobacter infection tended to decrease rather than increase gastric ethanol metabolism in mice. In humans, it remains to be established whether the observed decrease in antral ADH activity associated with H. pylori infection can lead to reduced gastric first-pass metabolism of ethanol.     

Helicobacter pylori and gastro-oesophageal reflux disease: association and clinical implications. To treat or not to treat with anti-H. pylori therapy?

BACKGROUND: It has been reported that patients are at risk of developing reflux oesophagitis after successful anti-Helicobacter pylori therapy, and the presence of the bacterium might be protective against the development of reflux oesophagitis. METHODS: Review of the literature. RESULTS: H. pylori is relevant to the management of oesophagitis because it increases the pH-elevating effect of proton-pump inhibitors. which increase the tendency of H. pylori gastritis to progress to atrophic gastritis, and because eradication of H. pylori increases the likelihood of oesophagitis. H. pylori increases basal gastrin levels, basal acid output, meal-stimulated maximal acid output and 24-h intragastric acidity. The effects on gastric acid production depend on the distribution of gastritis in the stomach. CONCLUSION: H. pylori eradication may induce or exacerbate gastro-oesophageal reflux by its influence on gastric acidity and the antisecretory action of proton-pump inhibitors.