Effects of Helicobacter pylori infection on gastric acid secretion and serum gastrin levels in Mongolian gerbils

BACKGROUND AND AIMS: Body gastritis caused by Helicobacter pylori infection appears to inhibit gastric acid secretion. The aim of this study was to determine the effects of H pylori infection on gastric acid secretion and clarify its mechanisms with reference to interleukin 1beta (IL-1beta). METHODS: (1) Mongolian gerbils were inoculated orally with H pylori. Before, six, and 12 weeks after inoculation, serum gastrin levels, gastric acid output, and IL-1beta mRNA levels in the gastric mucosa were determined. Pathological changes were also determined according to the updated Sydney system. (2) Effects of recombinant human IL-1 receptor antagonist (rhIL-1ra) on gastric acid output and serum gastrin levels were also determined. RESULTS: (1) Scores for activity and inflammation of gastritis and serum gastrin levels were significantly increased, and gastric acid output was significantly decreased six and 12 weeks after inoculation with H pylori. IL-1beta mRNA levels in the gastric mucosa were also elevated six and 12 weeks after inoculation with H pylori. (2) Acid output and serum gastrin levels in the infected groups returned to control levels after rhIL-1ra injection. CONCLUSIONS: Gastric acid secretion is decreased and serum gastrin levels are increased in Mongolian gerbils infected with H pylori. This change in gastric acid secretion appears to be mediated by IL-1beta induced by H pylori infection.     

Changes in gastric acid secretion assayed by endoscopic gastrin test before and after Helicobacter pylori eradication

BACKGROUND: It remains controversial whether or not Helicobacter pylori infection causes altered gastric acid secretion. A novel test for evaluating gastric acid secretion (endoscopic gastrin test; EGT) has recently been developed. AIM: To investigate by EGT the effects of H pylori eradication on the state of gastric acid secretion in patients with peptic ulcer. METHODS: Twenty six patients with duodenal ulcer and 33 with gastric ulcer, for all of whom H pylori infection had been documented, were studied by EGT, histological examination of gastric mucosa, and measurement of plasma gastrin levels before and one and seven months after H pylori eradication. RESULTS: In patients with duodenal ulcer, the mean EGT value before H pylori eradication was higher than that in H pylori negative controls, but it had decreased significantly seven months after the treatment. In contrast, the mean EGT value of patients with gastric ulcer before H pylori eradication was lower than that in H pylori negative controls, but it had increased one month after the treatment; this was followed by a slight decrease at seven months. In both groups, mean EGT values seven months after the treatment were not significantly different from the mean control value. CONCLUSIONS: The reduced acid secretion in gastric ulcer patients and gastric acid hypersecretion in duodenal ulcer patients were both normalised after the clearance of H pylori.     

Effect of age and Helicobacter pylori infection on gastric acid secretion

BACKGROUND: Whether gastric acid secretion decreases with age is still controversial. With the discovery of Helicobacter pylori, the association of this bacterium with gastric acid secretion has also been discussed. The aim of this study was to investigate the relationship between gastric acid secretion, age and H. pylori infection. METHODS: The presence of H. pylori infection, the grade of fundic atrophic gastritis (FAG), and gastric acid secretion were investigated in 280 subjects without localized lesions in the upper gastrointestinal tract. Helicobacter pylori infection was confirmed by Giemsa and immunohistochemical staining, and FAG of biopsy specimens was graded on a scale of 0-4. RESULTS: Both basal and maximal acid output decreased with age in H. pylori-positive subjects, while they did not change with age in H. pylori-negative subjects. Gastric acid secretion decreased with the progression of FAG. An age-correlated decrease in gastric acid secretion in H. pylori-positive subjects depended on an increasing prevalence of FAG with age. CONCLUSIONS: In the population studied, advancing age had no influence on gastric acid secretion in H. pylori-negative subjects. Gastric acid secretion decreases with age in H. pylori-positive subjects because of the increasing prevalence of FAG with age.     

Helicobacter pylori and gut hormones

Helicobacter pylori infection has been found to decrease the expression of antral somatostatin and to increase the release of the acid-stimulating hormone gastrin. The reversal of these changes in gut hormones by the eradication of H. pylori, and in-vivo and in-vitro studies in animals either infected with H. pylori or exposed to H. pylori-related materials may support the somatostatin-gastrin link theory in the pathophysiology of H. pylori infection. The following mechanisms have been proposed to explain the H. pylori infection-associated changes in gut hormones; (1) ammonia produced by H. pylori and monochloramine, (2) effect on somatostatin receptor subtype-2, (3) action of lipopolysaccharide from H. pylori on somatostatin receptor, (4) inflammatory cells and mediators, and (5) bacterial strain diversity. H. pylori infection can alter gastric acid secretion in both directions. The elevated acid secretion in patients with duodenal ulcer is decreased by H. pylori eradication, and is accompanied by the normalization of gut hormones in patients whose H. pylori-induced gastritis is limited to the antrum with hyperacidity. Corpus gastritis and the subsequent development of mucosal atrophy induced by H. pylori result in decreased acid secretion, although the mechanism underlying H. pylori-induced atrophy in some subjects remains unclear. Hypoacidity enhances corpus atrophy and increases gastrin secretion, mediated via a physiological suppression of somatostatin release, features that are also observed in H. pylori infection. Therefore, the capacity of acid secretion and distribution of gastritis or atrophy should be taken into consideration when we discuss the affect of H. pylori on gut hormones. Received: October 1, 2001 / Accepted: November 30, 2001     

Enhanced somatostatin secretion into the gastric juice with recovery of basal acid output after Helicobacter pylori eradication in gastric ulcers

BACKGROUND AND AIM: Antral somatostatin interacts with gastric acid secretion. We aimed to investigate the effect of eradication on gastric acid, somatostatin secretion and mucosal histology in gastric ulcer patients with Helicobacter pylori (H. pylori) infection. METHODS: Twenty-eight patients (21 male, 7 female) with H. pylori-positive gastric ulcer were treated with dual therapy. Before and 4-8 weeks after the therapy, the histology of biopsy specimens, basal acid output (BAO) and maximal acid output (MAO) after stimulation with tetragastrin were assessed. Somatostatin concentration in the gastric juice was measured by radioimmunoassay, and somatostatin output during either the basal or gastrin-stimulated period was also examined. RESULTS: Eradication was successful in 22 patients. Before treatment, the acid and somatostatin output were inversely related to the severity of neutrophil infiltration in the corpus and antrum, respectively. After successful eradication, improvement of histological inflammation and an increase in BAO, basal and gastrin-stimulated somatostatin output were observed. Eradication had no effect on atrophy and MAO. There was a positive correlation between gastric acid and somatostatin output in the basal or stimulated condition, irrespective of H. pylori infection. CONCLUSIONS: The present results suggest that recovery of gastric BAO may be caused by an improvement in corpus neutrophil infiltration, but not by an increase in parietal cell volume or a change in atrophy. Also, there was an increase in basal and gastrin-stimulated somatostatin-containing cell activity accompanied by improved antral neutrophil infiltration in the early phase after H. pylori eradication in gastric ulcers.     

Helicobacter pylori and gastric cancer

Abstract This review focuses on the similarities between the epidemiology of gastric cancer and the epidemiology of Helicobacter pylori. Their demographic patterns and the results of studies regarding familial and environmental risk factors are described. The association of gastric cancer and H. pylori infection with both gastric ulcer and chronic atrophic gastritis is also characterized and the possibility that a H. pylori infection could lead to gastric cancer is discussed.     

Helicobacter pylori infection prevents erosive reflux oesophagitis by decreasing gastric acid secretion

BACKGROUND: Helicobacter pylori infection is less prevalent and atrophic gastritis is less extensive in patients with reflux oesophagitis than those without it, but few studies have examined this relationship directly. AIMS: We investigated the relationship between H pylori infection, acid secretion, and reflux oesophagitis in Japanese subjects. SUBJECTS: A total of 105 patients with erosive reflux oesophagitis were compared with 105 sex and age matched patients without reflux oesophagitis. METHODS: The diagnosis of H pylori infection was made by histological examination of gastric mucosal biopsy specimens, rapid urease test, and detection of serum IgG antibodies. Acid secretion was assessed by the endoscopic gastrin test. RESULTS: H pylori infection was present in 36 patients with erosive reflux oesophagitis (34.3%) and in 80 control subjects (76.2%) (odds ratio 0.163, 95% confidence interval 0.09-0.29). Overall acid secretion was significantly greater in patients with reflux oesophagitis. Among H pylori positive patients, acid secretion was greater in patients with reflux oesophagitis than those without oesophagitis. CONCLUSION: In Japan, erosive reflux oesophagitis occurs most often in the absence of H pylori infection and gastric hyposecretion. Even in the presence of H pylori infection, reflux oesophagitis is more likely to develop in patients without gastric hyposecretion. H pylori infection may inhibit reflux oesophagitis by inducing hypoacidity.     

慢性多灶萎缩性胃炎患者胃酸分泌与幽门螺杆菌感染及血清胃泌素的关系

目的 研究慢性多灶萎缩性胃炎(BAG)胃酸分泌与幽门螺杆菌(Hp)感染及血清胃泌素的关系.方法 将200例确诊的慢性胃炎患者根据病理结果分为轻度、中度、重度BAG组及对照组(非萎缩性胃炎组),监测各组患者24小时胃内pH值的变化情况,并检测其幽门螺杆菌及血清胃泌素的含量,各组间进行比较.结果 (1)150例BAG患者中,Hp感染阳性率70%,随着胃粘膜萎缩程度的加重,Hp感染阳性率逐渐上升;(2)各组间血清胃泌素值比较:轻度萎缩组与非萎缩性胃炎组比较差异无显著性(P＞0.05),其余各组问比较差异有显著性(P＜0.05;(3)各组pH值分析结果:BAC胃黏膜轻度萎缩时,pH≤2时间百分比较非萎缩性胃炎组升高,pH＞4时间百分比及pH平均值、pH中位值均较非萎缩性胃炎组降低,中度及重度萎缩时pH≤2时间百分比逐渐降低,pH＞4时间百分比及pH平均值、pH中位值逐渐升高.结论 BAG的发生与Hp感染有关,胃粘膜萎缩程度与Hp感染的严重程度有关;BAG胃黏膜轻度萎缩时,血清胃泌素含量无明显变化;中、重度萎缩时,血清胃泌素含量降低;BAc胃黏膜轻度萎缩时,胃酸分泌增多;随着胃黏膜萎缩程度的加重,胃酸分泌逐渐减少.     

Pathophysiology of gastric acid secretion in patients with chronic renal failure: influence of Helicobacter pylori infection

OBJECTIVES: The incidence of gastroduodenal diseases is high in patients with chronic renal failure (CRF). However, gastric acidity in CRF has been reported to range in level from low to high. Moreover, it remains unknown whether Helicobacter pylori infection influences gastric acidity in such patients. Thus, we aimed to clarify the pathophysiological perturbation in gastric acidity and to determine the influence of H. pylori infection in CRF. DESIGN: Case-control study. SETTING: A university hospital. SUBJECTS: Twenty-seven patients with CRF and 24 control patients, presenting with either gastrointestinal symptoms, positive faecal occult blood, or anaemia (haemoglobin <10 g dL(-1)). MEASURES: The patients underwent gastroduodenal endoscopy with simultaneous determination of H. pylori infection. Gastric ammonium concentration, serum pepsinogen I and II, and basal gastrin level were measured. Thereafter, gastric acid secretion was monitored by 24-h intragastric acidity measurement with calculation of pH-3 holding time (%) (hours showing pH>3/24 h). RESULTS: In the CRF group, pH-3 holding time of H. pylori (+) subgroup was significantly greater than that of H. pylori (-) subgroup (71.2 +/- 32.4% vs. 32.8 +/- 30.0%, mean +/- SD; P=0.03). Pepsinogen I/II ratio was inversely correlated with pH-3 holding time in the control and CRF groups. Gastric ammonium concentration in CRF/H. pylori (+) subgroup (14.1 +/- 9.2 mmol L(-1)) was significantly higher than in CRF/H. pylori (-) (2.5 +/- 2.7 mmol L(-1); P=0.002) and control/H. pylori (+) subgroups (6.1 +/- 4.2 mmol L(-1); P=0.01). Serum gastrin level was significantly higher in the CRF group than in the control group (297 +/-343 pg mL(-1) vs. 116 +/- 69 pg mL(-1); P=0.02) as a whole. However, there was no significant correlation between serum creatinine and gastrin levels in the CRF group. Gastrin level in CRF/H. pylori (+) subgroup was significantly higher than in CRF/H. pylori (-), control/H. pylori (+), and control/H. pylori (-) subgroups (423 +/-398 pg mL(-1) vs. 113 +/- 79, 124 +/- 78, and 96 +/-43 pg mL(-1), respectively; P=0.01-0.03). Significant positive correlations amongst pH-3 holding time, ammonium and gastrin concentrations were found in the CRF group, but not in the control group. CONCLUSIONS: CRF without H. pylori infection primarily shows a tendency for high gastric acidity, but without hypergastrinaemia. Persistent H. pylori infection in CRF leads to decreased acidity and, consequently, to fasting hypergastrinaemia via a feedback mechanism. The hypoacidity in CRF with H. pylori infection appears to result from neutralization of acid by ammonia as well as from gastric atrophy. Thus, H. pylori infection status critically determines perturbation in gastric acidity and fasting gastrin level in CRF.     

Mechanism for gastric cancer development by Helicobacter pylori infection

Helicobacter pylori (H. pylori) infection plays a crucial role in the development of gastric cancer. There are two major pathways for the development of gastric cancer by H. pylori infection: the indirect action of H. pylori on gastric epithelial cells through inflammation, and the direct action of the bacteria on epithelial cells through the induction of protein modulation and gene mutation. Both pathways work together to promote gastric carcinogenesis.     

Hypergastrinemia after Helicobacter pylori infection is associated with bacterial load and related inflammation of the oxyntic corpus mucosa

BACKGROUND AND AIM: Helicobacter pylori infection causes hypergastrinemia. This study aimed to determine the association between serum gastrin and the severity of H. pylori-related gastric histology. METHODS: A total of 458 dyspeptic patients were included in this study after the absence of gastric malignancy was confirmed using endoscopy. The gastric specimens of each patient were collected from the antrum and corpus for the analysis of H. pylori-related histology changes by updated Sydney's system. Before endoscopy, the fasting blood samples were collected for gastrin analysis. RESULTS: The H. pylori-infected patients had higher gastrin levels than those without infection (P = 0.01). Gastrin levels were related to H. pylori density and acute and chronic inflammation scores in the corpus mucosa (P < 0.05), but not in the antral mucosa (P = NS). Gastrin levels were also not related to the presence of gastric atrophy. Multivariate regression showed that the gastrin level was only related to acute corpus inflammation. However, in the patients without infection, the gastrin level was also associated with acute corpus inflammation. Nevertheless, the patients with denser H. pylori infection were more likely to have acute corpus gastritis than those with lighter H. pylori infection, and thus presented with higher gastrin levels (P < 0.05). CONCLUSIONS: The increased level of gastrin of serum after H. pylori infection was associated with acute inflammation in the gastric corpus mucosa, but not in the antral mucosa. Denser H. pylori infection causes more severe corpus gastritis and thus may lead to a higher fasting level of gastrin of serum.     

Treatment of Helicobacter pylori and prevention of gastric cancer

Gastric cancer is the second commonest fatal malignancy in the world with a high incidence in China. Helicobacter pylori infection is an important factor in the pathogenesis of gastric cancer. Epidemiological studies have shown a strong causal relationship between H. pylori infection and gastric cancer. Animal studies also show that eradication of H. pylori infection, especially at the early stage, is effective in preventing H. pylori-related gastric carcinogenesis. H. pylori eradication leads to regression and prevents the progression of gastric precancerous lesions, but only in a minority of cases. H. pylori eradication appears to be the most promising approach in gastric cancer prevention. The current available data in human studies showed that H. pylori eradication can reduce the risk of developing gastric cancer and this strategy is more useful in patients without atrophic gastritis or intestinal metaplasia. A longer follow-up and additional studies are needed for better understanding this issue.     

Gastrin release and gastric acid secretion in the rat infected with either Helicobacter felis or Helicobacter heilmannii

Helicobacter pylori infection in humans has been shown to be associated with changes in gastric physiology, including exaggerated basal and meal-stimulated gastrin levels. This has been suggested to be due to the direct effects of the bacterium through inflammation and its urease enzyme. The gastric bacteria Helicobacter felis and Helicobacter heilmannii colonize the antrum of rats in large numbers and induce no significant inflammatory response. Thus, the direct effect of Helicobacter infection on gastric physiology, independent of gastritis, could be studied. Basal, freely fed and stimulated acid and gastrin levels were recorded from animals infected with H. felis, H. heilmannii or uninfected controls over a 30 week period. No significant difference was found between freely fed gastrin over 7 weeks or fasting gastrin over 24 weeks or basal and stimulated acid over 30 weeks between all three groups. Triple therapy did not alter gastrin or acid output. The antrum of all Helicobacter-infected rats was well colonized; triple therapy cleared H. felis but not H. heilmannii. Very little inflammation was seen in control or Helicobacter-infected animals. In conclusion, Helicobacter-induced effects on gastric physiology are unlikely to be due to direct bacterial effects, but are best explained by other factors (i.e. inflammatory damage).     

HLA-DQB1 locus and gastric cancer in Helicobacter pylori infection

BACKGROUND AND AIMS: It has been suggested that the incidence of digestive diseases associated with Helicobacter pylori is influenced by the strain diversity of H. pylori, factors involving the host or environment, and the duration of infection. The authors have previously reported that human leukocyte antigen (HLA)-DQB1*0401 plays an important role in the development of atrophic gastritis in H. pylori infected patients. The aim of the present study was to investigate the relationship between HLA-DQB1 genotype and cancer development. METHODS: HLA-DQB1 genotyping was performed by the PCR-RFLP method on 122 H. pylori-infected non-ulcer dyspepsia (NUD) patients, 53 gastric cancer patients and 28 uninfected controls. To reliably estimate the grade of atrophic gastritis, histological evaluation was performed. RESULTS: The allele frequency of DQB1*0401 was significantly higher in intestinal type cancer patients compared with age- and sex-matched H. pylori-infected NUD patients. There was no significant difference in the mean atrophic scores of the biopsy samples from the lesser curvature of the mid-corpus between these groups. CONCLUSIONS: HLA-DQB1*0401 is a useful marker for determining susceptibility to intestinal type gastric cancer.     

Endoscopic duodenitis, gastric metaplasia and Helicobacter pylori

BACKGROUND AND AIMS: The purpose of this study was to investigate the relationship between gastric metaplasia and Helicobacter pylori in patients with endoscopic duodenitis. METHODS: The subjects were 57 patients with endoscopic duodentitis with or without H. pylori-associated gastritis. Biopsy specimens were obtained from the stomach and duodenal bulb to assess the histological findings and H. pylori infection. Gastric metaplasia was divided into three types: complete, intermediate and incomplete, according to the amount of mucus in the metaplastic cells. In 10 H. pylori-positive patients, endoscopic and histological findings of duodenitis were compared before and after eradication of the bacteria. RESULTS: There was no significant difference in the extent of gastric metaplasia or the appearance and severity of endoscopic duodenitis between H. pylori-positive and -negative groups. The complete type of gastric metaplasia was frequently detected in the H. pylori-negative group, whereas the incomplete type was frequently observed in the H. pylori-positive group. After eradication of H. pylori, the incomplete type changed to the complete type with a decrease of histological inflammation. CONCLUSIONS: The complete type of gastric metaplasia occurred frequently without H. pylori infection, whereas the incomplete type was frequently associated with H. pylori infection.     

Eradication of Helicobacter pylori Infection in Patients with Non-Ulcer Dyspepsia: Effects on Basal and Bombesin-Stimulated Serum Gastrin and Gastric Acid Secretion

Background: This study evaluates the effect of eradicating Helicobacter pylori on basal and bombesin-stimulated gastric acid secretion and serum gastrin in non-ulcer dyspepsia. Methods: Before and 1 month after an attempt to eradicate H. pylori basal and bombesin-stimulated gastric acid outputs were measured in 23 patients. H. pylori was eradicated in 15 patients (group A) but not in the other 8 (group B). Incremental gastric acid output was calculated by subtracting basal from bombesin-stimulated values. Results: Basal acid output increased significantly (p = 0.01) after therapy in group A (Δ 1.6 ± 0.6 mmol/h) but not in group B (Δ0.2 ± 0.5 mmon). Incremental gastric acid output decreased distinctly (Δ-3.9 ± 1.4mmol/h) after therapy in group A (p = 0.02) but not in group B (Δ-2.2 ± 1.7mmol/h). Basal serum gastrin decreased significantly (p < 0.005) after therapy in group A (Δ -9 ± 4 pM) but not in group B (Δ-1 ± 2pM). Integrated serum gastrin responses to bombesin decreased markedly (p < 0.001) after therapy in group A (Δ-5.0 ± 1.6 nM60min) but slightly in group B (Δ-0.9 ± 1.3nM60min) (p < 0.05). Conclusions: In patients with non-ulcer dyspepsia basal serum gastrin concentrations decrease but basal gastric acid outputs increase after eradication of H. pylori. Bombesin-induced increments in gastric acid output, however, decrease in parallel with gastrin release.     

Epidemiology of gastric cancer in relation to diet and Helicobacter pylori infection

Abstract Gastric cancer is the second most common fatal malignancy in the world. In China, gastric cancer is now the second most common malignancy, while in Hong Kong, the mortality rate ranked fourth among all cancers in 1995. Dietary factors in gastric carcinogenesis came mostly from case-control studies. N-Nitroso compounds from dietary sources such as preserved, smoked and salted foods were found to be associated with gastric cancer. ß-Carotene, selenium and α-tocopherol have been shown in an intervention study to be favourable in the reduction of stomach cancer mortality. Fruits and vegetables showed the most consistent results of inverse association with gastric cancer. Dietary salt intake in preserved or salted foods is also shown to be associated with gastric cancer. Tea drinking, especially green tea, has a protective effect against gastric cancer as shown in some studies. Prospective case-control studies of the association between Helicobacter pylori infection and the subsequent development of gastric cancer showed that the odds ratio ranged from 2.8 to 6.0. However, results of similar case-control studies in countries with a high frequency of gastric cancer are controversial. Infection with H. pylori leads to changes in the vitamin C content of gastric juice, reactive oxygen metabolites, epithelial cell proliferation and apoptosis. Recently, CagA-positive strains were found to be associated with gastric cancer and also duodenal ulcers. The exact role of H. pylori in gastric carcinogenesis is still under investigation. Large-scale intervention studies are underway to examine dietary supplementation, H. pylori infection and gastric cancer. Helicobacter pylori eradication for gastric cancer prevention is being conducted in China and other parts of the world. In high-risk areas, for example in China, a combination approach including H. pylori eradication and dietary supplementation may be necessary.