Prevalence and heterogeneity of Helicobacter pylori in gastric biopsies of patients with gastroduodenal diseases

Helicobacter pylori is a risk factor for development of peptic ulcers and adenocarcinoma of distal stomach. There are several highly specialized virulence factors, such as the production of sialic acid-specific hemagglutinins, cytotoxins and enzymes. This study was designed to study the in vivo prevalence of H. pylori in patients with gastroduodenal diseases, the in vivo correlation between H. pylori infection and blood group O, and the heterogeneity of H. pylori isolates in central Taiwan. We enrolled 776 symptomatic patients residing in the central Taiwan area. The age-specific in vivo prevalence of H. pylori in patients with gastroduodenal diseases increased from 11.1% in those between the ages of 1 to 20, 73.1% in those between the ages of 21 and 30, and to 79.8% in those between the ages of 51 and 60. In conclusion, H. pylori was present in 70% of biopsied specimens of symptomatic patients with gastroduodenal diseases and had the highest incidence (86%) in patients with peptic ulcers. The prevalence of H. pylori cag A expression positive strains in central Taiwan was 92.5%. This study has also demonstrated the high correlation between H. pylori and the blood group O-positive patients with gastroduodenal diseases. The prevalence of H. pylori infection in blood O-positive patients in central Taiwan was 86.4%.     

Role of Helicobacter pylori plasticity region genes in development of gastroduodenal diseases

The plasticity region of Helicobacter pylori is a large chromosomal segment including isolate-specific open reading frames with characteristics of pathogenicity islands. It remains unclear whether genes in the plasticity region play a role in the pathogenesis of gastric mucosal inflammation and gastroduodenal disease. Our aim was to assess the role of selected genes in the plasticity region in relation to risk of H. pylori-related disease and the severity of gastric mucosal damage. We used PCR to study the relation of disease outcome and mucosal damage with four genes in the H. pylori plasticity region (jhp0940, jhp0945, jhp0947, and jhp0949) from isolates obtained from both Western (n = 296) and East Asian (n = 217) patients. The prevalence of jhp0945, jhp0947, and jhp0949 differed significantly between Western and East Asian isolates. In Western isolates, the presence of jhp0945 was significantly associated with gastric ulcer, duodenal ulcer, and gastric cancer (odds ratios [95% confidence intervals]: 2.27 [1.04 to 4.98], 1.86 [1.03 to 3.34], and 1.92 [1.03 to 3.56], respectively). jhp0940-positive Western isolates were significantly associated with absence of gastric ulcer or duodenal ulcer (0.21 [0.05 to 0.94] and 0.31 [0.12 to 0.78], respectively). No significant difference was observed between inflammatory cell infiltration or atrophy and the presence or absence of plasticity region genes. The outcome of H. pylori infections varies widely geographically. These data suggest a possible role for difference in the prevalence of plasticity region genes in the geographic variation in H. pylori-related diseases.     

TGFB1 gene polymorphisms: their relevance in the susceptibility to Helicobacter pylori-related diseases

Recent studies have revealed elevated expression of transforming growth factor beta1 (TGF-beta1) in gastric mucosa of patients with gastric cancer (GC) and those undergoing ulcer repair. As production of TGF-beta1 is genetically regulated, we aimed to assess whether functional polymorphisms of the TGFB1 gene are involved in susceptibility to and clinical characteristics of Helicobacter pylori-related diseases. DNA from 142 unrelated Spanish patients with GC, 200 with peptic ulcer and 342 healthy controls was typed for the MspA1I T+869C, and the Sau96I G+915C polymorphisms of the TGFB1 gene using polymerase chain reaction and RFLP analysis. H. pylori infection and CagA/VacA antibody status were determined by Western blot in patients and controls. H. pylori infection (odds ratio (OR): 11.44; 95% confidence interval (CI): 4.45-29.42; P<0.001) and non-steroidal anti-inflammatory drugs (OR: 5.07; 95% CI: 2.53-10.16; P<0.001) were identified as independent risks factors for duodenal ulcer (DU), whereas the TGFB1+869(*)C/C genotype was associated with reduced risk of developing the disease (OR: 0.32; 95% CI=0.15-0.68; P=0.003). Our results show that the TGFB1 T+869C gene polymorphism is involved in the susceptibility to DU and provide further evidence that host genetic factors play a key role in the pathogenesis of H. pylori-related diseases.     

TLR4 single-nucleotide polymorphisms alter mucosal cytokine and chemokine patterns in Mexican patients with Helicobacter pylori-associated gastroduodenal diseases

Helicobacter pylori is associated with peptic ulcer and gastric adenocarcinoma. Toll-like receptors (TLRs) participate in H. pylori recognition, and single-nucleotide polymorphisms (SNPs) in TLRs are associated with impaired immune response. We aimed to evaluate the association of TLR2/R753Q and TLR4/D299G/T399I SNPs with gastroduodenal diseases; and study the effect of SNPs on cytokine and chemokine expression in the gastric mucosa. Study included 450 Mexican patients with gastroduodenal diseases. SNPs in TLRs 2 and 4 genes were analyzed by allele-specific PCR. Cytokines and chemokines were assessed by qRT-PCR and immunoassay. TLR4/D299G/T399I polymorphisms were more frequent in duodenal ulcer and showed a trend in gastric cancer, when compared with non-atrophic gastritis. Patients with TLR4 polymorphisms expressed significantly lower levels of IL-1beta, IL-6, IL-8 and GRO-alpha; and higher levels of TNF-alpha, IL-10, MCP-1 and MIP-1alpha . SNPs in TLR4 gene had an association with severe H. pylori-associated disease and with modified pattern of inflammatory cytokines and chemokines in the gastric mucosa. These results suggest that TLR4 SNPs contributes importantly to the clinical outcome of H. pylori infection.     

Vascular endothelial growth factor and neo-angiogenesis in H. pylori gastritis in humans

Host response plays a major role in the pathogenesis of Helicobacter pylori-induced gastroduodenal disease including adenocarcinoma of the distal stomach. Vascular endothelial growth factor (VEGF) is an important modulator of gastric mucosal repair and is overexpressed in gastric cancer. The present study sought to evaluate the expression of VEGF in the gastric mucosa of H. pylori-infected and H. pylori-non-infected dyspeptic patients. Fifteen H. pylori-infected and 15 H. pylori-non-infected dyspeptic patients were studied. Diagnosis of H. pylori infection was based on rapid urease test and histology. VEGF protein expression was assessed by western blotting. VEGF mRNA expression was assessed by RT-PCR. VEGF localization in the gastric mucosa and neo-angiogenesis were determined by immunohistochemistry. VEGF protein and mRNA expression was significantly greater in H. pylori-infected than in non-infected patients. Immunohistochemistry showed that VEGF expression was more intense in the gastric gland compartment of H. pylori-infected mucosa than in the non-infected mucosa. The increase in VEGF expression was associated with a significant increase in neo-angiogenesis as assessed by determination of CD34-positive micro-vessels. H. pylori gastritis is therefore associated with up-regulation of VEGF expression, which parallels the increased formation of blood vessels in the gastric mucosa. It is postulated that increased VEGF expression and neo-angiogenesis may contribute to H. pylori-related gastric carcinogenesis.     

Immunoglobulin G1 antibody response to Helicobacter pylori heat shock protein 60 is closely associated with low-grade gastric mucosa-associated lymphoid tissue lymphoma.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is related to Helicobacter pylori infection. Specifically, it has been pointed out that pathogenesis of MALT lymphoma involves the 60-kDa heat shock protein (hsp60). To investigate humoral immune responses to the H. pylori hsp60 in patients with gastroduodenal diseases and patients with MALT lymphoma, the hsp60 of H. pylori was expressed with a glutathione S-transferase fusion protein and was purified (recombinant hsp60). Sera were obtained from H. pylori-positive patients with gastroduodenal diseases (MALT lymphoma, n = 13; gastric ulcer, n = 20; duodenal ulcer, n = 20; gastritis, n = 20) and from H. pylori-negative healthy volunteers (n = 9). Sera from patients with MALT lymphoma were also obtained at two times: before and after eradication therapy. Antibodies to hsp60 and H. pylori were assessed by enzyme-linked immunosorbent assay. The levels of immunoglobulin G (IgG) antibodies to the hsp60 of H. pylori-positive patients with gastroduodenal diseases were significantly elevated compared to those in the controls. The levels of IgG1 antibodies to hsp60 were elevated and correlated with the levels of anti-H. pylori antibodies in patients with MALT lymphoma. Humarol immunity against hsp60 may be important and relevant to gastroduodenal diseases induced by H. pylori infection.     

Eradication of Helicobacter pylori in clinical situations

Helicobacter pylori is prevalent worldwide, especially in developing countries, and is associated with several upper gastrointestinal diseases. Since it is present in over 90% of duodenal ulcer patients, empirical eradication in these patients is often recommended. In gastric ulcer patients, eradication is indicated only after the infection is confirmed. Testing for H. pylori infection should be carried out in patients with peptic ulcer hemorrhage, because eradication has been shown to reduce recurrent bleeding. Both H. pylori and NSAIDs are risk factors for peptic ulceration, and it is reasonable to screen for and eradicate H. pylori infection in peptic ulcer patients taking NSAIDs. H. pylori is a group I carcinogen for gastric adenocarcinoma, and should be eradicated for the primary prevention of this cancer. Eradication of this organism has been reported to result in regression of early low-grade mucosa-associated lymphoid tissue lymphoma. The role of H. pylori infection in the causation of gastroesophageal reflux and non-ulcer dyspepsia is not clearly established. Several tests are available for the diagnosis of H. pylori infection. These include invasive tests, such as histology, culture and urease test, and non-invasive tests, such as serology, urea breath test and stool antigen test. The choice of test is determined by clinical indication, pretest probability of infection, as well as the availability, cost, sensitivity and specificity of the test. H. pylori eradication therapy using proton pump inhibitor with clarithromycin and amoxycillin for 7 days has a success rate of 85-90%. Improved living standard and sanitation are vital in the control of H. pylori transmission and infection. Future development may include the use of vaccines against H. pylori, and therapies specifically targeting cagA strains of the bacteria.     

幽门螺杆菌感染与老年人上消化道疾病关系的临床研究

目的通过长期随访临床观察幽门螺杆菌（Helicobcter pylori,Hp）相关胃炎易继发消化性溃疡和胃癌。Hp感染率有随着年龄增长而升高的趋势,阐明Hp与老人上消化道疾病的关系。方法620例均为门诊和住院患者,按年龄分为老年组≥60岁272例,其中男180例,女92例,中位年龄65岁;青壮年组〈60岁348例,其中男213例,女135例,中位年龄36岁。上消化道疾病诊断：患者在电子胃镜下肉眼观察其胃和十二指肠粘膜,并在病变部位取材活检,送病理检查,以确定疾病性质（诊断）。Hp检测方法：采用^14C尿素呼气试验方法。患者于胃镜检查结束后或在上午空腹时接受试验。结果620例患者中Hp阳性371例,阳性率60%。其中老年组Hp阳性率为66.2%（180/272）,明显高于青壮年的54.9%（191/348）,差异有统计学意义（P〈0.01）。老年组慢性胃炎和胃溃疡Hp阳性率为66.4%及75.6%,均高于青壮年组的43.9%和41.0%,差异有统计学意义（P〈0.01）。老年组胃溃疡及胃癌患病率高于青壮年组差异有统计学意义（P〈0.05或〈0.01）。结论通过研究提示Hp感染在老年慢性胃炎和胃溃疡发病学上,具有比青壮年更大的重要性。同时,支持年龄与Hp成正相关的观点,说明Hp感染与上消化道疾病的发病关系密切。     

Relation between seroreactivity to low-molecular-weight Helicobacter pylori-specific antigens and disease presentation

The identification of Helicobacter pylori-strain specific factors that correlate with clinical outcome has remained elusive. We investigated possible relationships between a group of H. pylori antigens and clinical outcome and compared an immunoblot assay kit (HelicoBlot, version 2.1 [HB 2.1]; Genelabs Diagnostics) with an established serological test, the high-molecular-weight cell-associated protein test (HM-CAP). We used sera from 156 Thai patients with different disease presentations, including 43 patients with gastric cancer, 64 patients with gastric ulcer, and 49 patients with nonulcer dyspepsia (NUD). HB 2.1 was compared to HM-CAP as a diagnostic test for H. pylori infection. The seroprevalence of H. pylori was significantly higher among gastric cancer patients than among patients with NUD (93 and 67%, respectively; P < 0.01). Among the H. pylori-seropositive patients, the presence of the antibody to the 37,000-molecular-weight antigen (37K antigen) was inversely related to the presence of gastric cancer (e.g., for gastric cancer patients compared with NUD patients, odds ratio [OR] = 0.28 and 95% confidence interval [CI] = 0.1 to 0.8). The presence of antibody to the 35K antigen was higher in gastric ulcer patients than in NUD patients (OR = 11.5; 95% CI = 2.4 to 54.3). The disease associations of antibodies to the 35K and 37K antigens are consistent with the possibility that these antigens are either indirect markers for H. pylori-related diseases or have specific active or protective roles in H. pylori-related diseases.     

Protection of BALB/c mice against experimental Helicobacter pylori infection by oral immunisation with H pylori heparan sulphate-binding proteins coupled to cholera toxin beta-subunit

The presence of Helicobacter pylori in the gastroduodenal mucosae is associated with chronic active gastritis, peptic ulcers and gastric cancers such as adenocarcinoma and low-grade gastric B-cell lymphoma. In response to the presence of antibiotic-resistant strains, the use of vaccines to combat this infection has become an attractive alternative. The present study used a murine model of infection by a mouse-adapted H. pylori strain to determine whether infection in BALB/c mice can be successfully eradicated by intragastric vaccination with H. pylori heparan sulphate-binding proteins (HSBP) covalently coupled to the beta-subunit of cholera toxin (CTB). It was shown that vaccination confers protection against exposure of BALB/c mice to the pathogen, as revealed by microbiological, histopathological and molecular methods.     

Peptic ulceration may be a hormonal deficiency disease

Evidence is reviewed that Helicobacter pylori infection may cause a deficiency of the hormone secretin that allows peptic ulcer disease to develop by impairing the body's defenses to gastric acid. Secretin is released into the circulation from the S-cells of the duodenal crypts in response to gastric acid entering the duodenum. Once in the circulation, secretin has five well-documented effects that protect the upper intestine from gastric acid: it stimulates secretion of bicarbonate rich exocrine pancreatic juice; it stimulates secretion of alkaline bile; it stimulates secretion of alkaline mucus from the duodenal submucosal glands of Brunner; it inhibits the humoral phase of gastric secretion; and it inhibits gastric motility, thereby delaying gastric emptying. Impaired secretin release and reduced duodenal S-cells have been documented in peptic ulcer patients compared with control patients. Clinical evidence that patients with H. pylori infection and peptic ulceration have increased gastric secretion and motility and decreased duodenal bicarbonate response to gastric acid, all of which normalize after eradication of the infection, could be explained by reversible impairment of the secretin mechanism. Gastric metaplasia in the duodenum with H. pylori infection is known to reduce the S-cell population. The fact that not all patients with H. pylori infection develop peptic ulceration suggests that degree of secretin deficiency determined by extent of the infection must reach a critical level for peptic ulceration to occur. Peptic ulceration may be a hormonal deficiency disease, a result of secretin deficiency caused by H. pylori infection. It may be the first example of a specific hormonal deficiency disease caused by a specific bacterial infection.     

Serum antibody positivity for distinct Helicobacter pylori antigens in benign and malignant gastroduodenal disease

Infection with Helicobacter pylori may be associated with a variety of gastroduodenal diseases. Although H. pylori infection is common, peptic ulcer disease and gastric cancer occur in only a small minority of infected persons. This work was intended to correlate the pathological findings with the serological response to certain H. pylori antigens. Serum samples were taken from 285 patients who underwent gastroscopy. H. pylori infection was diagnosed by histology, culture or rapid urease test (RUT). Serum IgG reactivity against H. pylori-specific antigens was studied by Western blot. There was a significant association between the diagnosis of gastric cancer and the presence of IgG antibodies against the 19.5, 33 and 136 kDa (CagA) antigens. Comparing all H. pylori-positive patients with the gastric cancer group for the presence of the 19.5, 33 and 136 kDa (CagA) antigens, the results were as follows: chi2: 17.482, p < 0.001, power P = 0.994, odds ratio (OR) for the presence of gastric cancer: 19.5 (95% confidence interval (CI): 4.11-92.56). Antibodies against CagA alone or other bands (except 33 and 19.5 kDa antigens), as well as the age of patients were not related to a diagnosis of gastric cancer. Male patients were more likely to develop duodenal ulcer. IgG antibodies against the 19.5, 33 and 136 kDa (CagA) antigens could be helpful to identify patients at enhanced risk for the development of gastric cancer.     

Helicobacter pylori detection and antimicrobial susceptibility testing

The discovery of Helicobacter pylori in 1982 was the starting point of a revolution concerning the concepts and management of gastroduodenal diseases. It is now well accepted that the most common stomach disease, peptic ulcer disease, is an infectious disease, and all consensus conferences agree that the causative agent, H. pylori, must be treated with antibiotics. Furthermore, the concept emerged that this bacterium could be the trigger of various malignant diseases of the stomach, and it is now a model for chronic bacterial infections causing cancer. Most of the many different techniques involved in diagnosis of H. pylori infection are performed in clinical microbiology laboratories. The aim of this article is to review the current status of these methods and their application, highlighting the important progress which has been made in the past decade. Both invasive and noninvasive techniques will be reviewed.     

Modes of adherence of Helicobacter pylori to gastric surface epithelium in gastroduodenal disease: a possible sequence of events leading to internalisation

We have investigated various modes of adherence of Helicobacter pylori to the human gastric epithelium, using transmission electron microscopy, in biopsies from nine patients with peptic ulcer disease and from four patients with chronic active gastritis. H. pylori was demonstrated in abundance in all cases within the surface mucous layer. In all ulcer- and in one out of four gastritis patients H. pylori was shown in close proximity to the gastric epithelium, with concurrent alterations in the configuration of microvilli and the apical cytoplasmic region of gastric cells. Previously described modes of H. pylori adherence were confirmed, such as loose attachment with fibrillar-like strands, firm attachment with pedestal formation, invasion in the intercellular spaces, and invagination with "cup" formation. Moreover, in many cases a fusion between the bacterial outer layer and gastric cell membranes was evident. In four cases (31%; three with active and one with past ulcer disease) viable H. pylori was found in the cytoplasm of gastric mucous cells. Our results support the hypothesis that the different modes of adherence of H. pylori represent a stepwise, possibly sequential, process which in a significant number of cases leads to internalisation of the organism. The invariable occurrence of adhesion and more frequent internalisation of H. pylori in ulcer patients may suggest a link with the pathogenesis of peptic ulcer disease.     

Nodular gastritis and pathologic findings in children and young adults with Helicobacter pylori infection

PURPOSE: The aim of this study was to investigate the pathologic characteristics of nodular gastritis in children and young adults infected with Helicobacter pylori (H. pylori). MATERIALS AND METHODS: A total of 328 patients were enrolled in this study, and the diagnosis of H. pylori infection was done with gastroduodenal endoscopy concomitant with a CLO(TM) test and pathologic analysis of the biopsy specimens. Diagnoses of normal, superficial gastritis, nodular gastritis, and peptic ulcer disease were made from the gastroduodenal endoscopic findings. The density of H. pylori organisms in the gastric mucosa was rated as normal, mild, moderate, or marked. The pathologic findings of nodular gastritis were based on the histopathologic findings of inflammation, immune activity, glandular atrophy and intestinal metaplasia. Each of these findings was scored as either normal (0), mild (1), moderate (2), or marked (3) according to the updated Sydney system and using visual analog scales. The gastritis score was the sum of the four histopathologic scores. RESULTS: In this study, nodular gastritis (50.6%) was most common, and mild density (51.5%) H. pylori infection was also common upon microscopic examination. Intestinal metaplasia occurred in 9 patients (2.7%). CONCLUSION: Logistic regression revealed a significant increase in the incidence of nodular gastritis with gastritis score (p=0.008), but not an association with sex, age, or H. pylori density. Gastritis score was the only significant factor influencing the occurrence of nodular gastritis. Intestinal metaplasia, which was originally thought to be a pre-malignant lesion, occurred in 2.7% of the patients with H. pylori infection.     

Antibiotic resistance of Helicobacter pylori from patients in Ile-Ife, South-west, Nigeria

Background: Helicobacter pylori has become recognized as a major cause of gastroduodenal diseases in man. Evidence indicates that once acquired, H. pylori persists, usually for life unless eradicated by antimicrobial therapy. Over the past few years, we have accumulated some knowledge of the epidemiology of H. pylori in Ile-Ife, South-West Nigeria. In one collaborative study, we detected H. pylori in 195 (73%) patients referred for endoscopy at Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC). Furthermore we have observed a variegated gastric inflammatory response and atrophy including atrophic pangastritis but are yet to demonstrate MALToma in any of our patients. In addition we have demonstrated that dental plaque is a possible source of gastric H. pylori infection and such an endogenous source could account for difficulty in eradication leading to re-infection. Presently, infected patients are treated with standard combination therapy made up of amoxycilin and ciprofloxacin with a proton pump inhibitor/bismuth. Reports however have shown that the incidence of antimicrobial resistance in Helicobacter pylori is a growing problem and which has been linked with failures in treatment and eradication. Given this situation it has become necessary to have information about the susceptibility of isolates to particular antimicrobial agents before the selection of an appropriate treatment regimen. Objectives: More recently, we sought to study antimicrobial susceptibility of locally isolated H. pylori strains. Methods: We subjected 32 isolates to antimicrobial susceptibility testing against seven agents. Results: All the isolates showed multiple acquired antimicrobial resistance as they were all resistant to amoxicillin, clarithromycin, metronidazole, while 29/31, 27/31 showed resistance to rifampicin and tetracycline respectively. Five (15.6%) of these isolates showed resistance to ciprofloxacin. Conclusions: Our findings suggest that H. pylori strains isolated within our study environment have acquired resistance to all the commonly prescribed antibiotics. On the basis of the findings it would be necessary to re-evaluate the eradication treatment regime in our setting.     

Helicobacter pylori & gastric disease

Since the discovery of Helicobacter pylori(H. pylori), causal linkage between H. pylori infection and some of gastric disease has been generally accepted from the results of many studies. Indeed the usefulness of H. pylori eradication therapy for acute gastritis, peptic ulcer, gastric polyp and MALT lymphoma etc. has been reported. In the low grade MALT lymphoma, the regression rate by this therapy is about 70%. On the other hand, we should pay the caution to several adverse effects, such as drug resistance and GERD, of H. pylori eradication therapy. However, based on the several results of comparative studies between antibiotic therapy and the other one, the antibiotic therapy for peptic ulcer is only covered by national health insurance at present. The reversibility of gastric precancerous conditions such as mucosal atrophy, intestinal metaplasia and dysplasia by antibiotic therapy has been studied, but its significance is not clear yet. In animal experiment, H. pylori infection induced gastric adenocarcinoma in Mongolian Gerbils. However, this phenomenon is limited to this kind of animal only. To proof the causal link between H. pylori infection and genesis of gastric cancer in human being, clinical intervention trials are ongoing in the world. If these trials can clarify it, the H. pylori eradication therapy will be established as preventive measure for gastric carcinogenesis.     

Histopathological changes in gastric mucosa colonized by H. pylori

Helicobacter pylori (H. pylori), infection has been linked to acute and chronic gastritis, non-ulcer-dyspepsia, peptic ulcer, gastric adenocarcinoma and gastric non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue (MALT). The epithelial changes in H. pylori colonized gastric mucosa are easy to recognize in routine Haematoxylin & Eosin stained sections and are so distinctive that they can serve as a helpful histological indicator for the presence of H. pylori in gastric biopsies. The histopathology of seventy-five gastric biopsies showing colonization by H. pylori was studied. Histologically, the H. pylori colonized gastric epithelium showed characteristic changes that were topographically related to the bacteria. These changes included irregular surface, epithelial pits, individual cell dropout and microerosion, which were specific for H. pylori colonization. These were absent in areas not colonized by H. pylori and in 20 consecutive H. pylori negative gastric biopsies seen during the same study period. As specific treatment for H. pylori infection is available, identification of H. pylori colonization in gastric biopsies should be attempted in all cases of gastritis, peptic ulcers and non-ulcer-dyspepsia.     

Expression of inflammatory mediators in the otitis media induced by Helicobacter pylori antigen in mice

Helicobacter pylori is a Gram-negative bacterium that is recognized as one of the key factors in gastric diseases such as gastritis, peptic ulcer and gastric cancer. Recent studies have shown relationships between H. pylori and extra-digestive diseases, and the presence of H. pylori in the middle ear and upper respiratory tract has been reported. However, the role of H. pylori in middle ear disease remains unclear. The present study demonstrated that H. pylori whole-cell protein directly induces macrophage migration inhibitory factor, macrophage inflammatory protein 2, interleukin 1 beta and tumor necrosis factor alpha in middle ear epithelium in mice, and severe proliferation of inflammatory cells was observed in middle ear cavity inoculated with H. pylori whole-cell protein. In addition, trans-tympanic injection of macrophage migration inhibitory factor up-regulated expression of macrophage inflammatory protein 2 in the middle ear. These findings indicate that H. pylori infection causes immunological inflammation in middle ear epithelium, and H. pylori may play a significant role in otitis media.