Helicobacter pylori and gastric cardia cancer: What do we know about their relationship?

The incidence of gastric cardia cancer is increasing around the world. Since the discovery of Helicobacter pylori (H. pylori), numerous studies have proved that it is a causative factor for many kinds of digestive system tumors. Although the literature on gastric cardia cancer and H. pylori is not scarce, there are still many controversies on the relationship between gastric cardia cancer and H. pylori. Many Western research results showed that there was a negative or no correlation between H. pylori infection and gastric cardia cancer, but in several studies in Asian countries, such as China, H. pylori was demonstrated to be a risk factor for gastric cardia cancer. Therefore, we intended to analyze the related studies to find out the relationship between H. pylori and gastric cardia cancer and find out the causes of the above controversies. We also conducted a meta-analysis of the relationship between cagA positive expression of H. pylori and gastric cardia cancer, to find out whether there is an effect between those two. The primary purpose of this paper was to explore the relationship between gastric cardia cancer and H. pylori. Through analysis, the study showed the reasons for the controversies mentioned above: (1) Geographical factors could affect the relationship between H. pylori and gastric cardia cancer; (2) The definition of gastric cardia cancer in various studies is inconsistent. The result of a meta-analysis about the relationship between H. pylori virulence factor cagA and gastric cardia cancer showed that there was no relationship between these two.     

Current guidelines for Helicobacter pylori treatment in East Asia 2022: Differences among China,Japan, and South Korea

Helicobacter pylori (H. pylori) infection is highly prevalent in East Asia. The overall seroprevalence rate of H. pylori infection is 44.2% in China, 37.6%-43.2% in Japan, and 51.0% in South Korea. H. pylori can cause peptic ulcer disease and gastric cancer. East Asian countries have high rates of gastric cancer (age-standardized incidence rate: 20-30 per 100000). The Kyoto global consensus report emphasized that H. pylori gastritis should be considered the main cause for the development of gastric cancer. H. pylori treatment guidelines in China, Japan, and South Korea have recently been revised according to data from each of those countries. However, emerging antibiotic resistance is an important barrier to H. pylori eradication. The recommended H. pylori treatment regimens differ among those three East Asian countries. In this review, recent guidelines and up-to-date research on H. pylori treatment regimens from China, Japan, and South Korea are discussed.     

Immune response to Helicobacter pylori infection and gastric cancer development

Gastric adenocarcinoma is a global health concern, and Helicobacter pylori (H. pylori) infection is the main risk factor for its occurrence. Of note, the immune response against the pathogen seems to be a determining factor for gastric oncogenesis, and increasing evidence have emphasized several host and bacterium factors that probably influence in this setting. The development of an inflammatory process against H. pylori involves a wide range of mechanisms such as the activation of pattern recognition receptors and intracellular pathways resulting in the production of proinflammatory cytokines by gastric epithelial cells. This process culminates in the establishment of distinct immune response profiles that result from the cytokine-induced differentiation of T naïve cells into specific T helper cells. Cytokines released from each type of T helper cell orchestrate the immune system and interfere in the development of gastric cancer in idiosyncratic ways. Moreover, variants in genes such as single nucleotide polymorphisms have been associated with variable predispositions for the occurrence of gastric malignancy because they influence both the intensity of gene expression and the affinity of the resultant molecule with its receptor. In addition, various repercussions related to some H. pylori virulence factors seem to substantially influence the host immune response against the infection, and many of them have been associated with gastric tumorigenesis.     

New insights of Helicobacter pylori host-pathogen interactions: The triangle of virulence factors,epigenetic modifications and non-coding RNAs

Helicobacter pylori (H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important. H. pylori also modulates inflammatory and autophagy process to intensify its pathogenicity. From the host regard, different genetic factors particularly affect the development of gastric cancer. Indeed, epigenetic modifications, MicroRNA and long non-coding RNA received more attention. Generally, various factors related to pathogen and host that modulate gastric cancer development in response to H. pylori need more attention due to develop an efficacious therapeutic intervention. Therefore, this paper will present a brief overview of host-pathogen interaction especially emphases on bacterial virulence factors, interruption of host cellular signaling, the role of epigenetic modifications and non-coding RNAs.     

Application of traditional Chinese medicine in treatment of Helicobacter pylori infection

Helicobacter pylori (H. pylori) has a high rate of infection and antibiotic resistance and poses a serious threat to human life. One of the main strategies to overcome drug resistance is to develop new treatment plans. Traditional Chinese medicine (TCM) that is commonly used to treat many diseases in China can reduce drug resistance and increase the eradication rate of H. pylori. In this paper, we review the research progress on TCM in the treatment of H. pylori infection. The mechanism of action of TCM is reviewed and research and applications of TCM in the treatment of H. pylori are demonstrated. Finally, we discuss problems confronting the use of TCM for the treatment of H. pylori infection and propose possible solutions. In addition, the plans of TCM in H. pylori treatment were also screened: Dampness-heat syndrome in the spleen and stomach, deficiency of spleen and stomach, and cold-heat complicated syndrome, and the effective components therein are studied. The antibacterial effect of TCM is relatively slow; for rapid improvement of the treatment effect of refractory H. pylori gastritis, we provide an appropriate treatment regime combining TCM and Western medicine with immune-regulatory and synergistic antibacterial effects.     

Treatment of Helicobacter pylori infection: Current and future insights

Helicobacter pylori (H. pylori) is an important major cause of peptic ulcer disease and gastric malignancies such as mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma worldwide. H. pylori treatment still remains a challenge, since many determinants for successful therapy are involved such as individual primary or secondary antibiotics resistance, mucosal drug concentration, patient compliance, side-effect profile and cost. While no new drug has been developed, current therapy still relies on different mixture of known antibiotics and anti-secretory agents. A standard triple therapy consisting of two antibiotics and a proton-pump inhibitor proposed as the first-line regimen. Bismuth-containing quadruple treatment, sequential treatment or a non-bismuth quadruple treatment (concomitant) are also an alternative therapy. Levofloxacin containing triple treatment are recommended as rescue treatment for infection of H. pylori after defeat of first-line therapy. The rapid acquisition of antibiotic resistance reduces the effectiveness of any regimens involving these remedies. Therefore, adding probiotic to the medications, developing anti-H. pylori photodynamic or phytomedicine therapy, and achieving a successful H. pylori vaccine may have the promising to present synergistic or additive consequence against H. pylori, because each of them exert different effects.     

Helicobacter pylori infection and small intestinal bacterial overgrowth–more than what meets the eye

Helicobacter pylori (H. pylori) infection is very common and affects a significant proportion of the world population. In contrast, the prevalence of small intestinal bacterial overgrowth (SIBO) in the general population is not well understood. There can be coexistence of both disease states in a given patient and their clinical symptoms may also overlap with one and another. There is no clear clinical guidelines for testing for and treating SIBO in patients with H. pylori infection. This review article explores the available evidence on the relationship between H. pylori infection and SIBO, diagnosis and treatment of these entities and also comments on associated non-gastrointestinal conditions.     

Maintaining the metabolic homeostasis of Helicobacter pylori through chronic hyperglycemia in diabetes mellitus: A hypothesis

Helicobacter pylori (H. pylori) infection occurs in almost half of the world's population, most of whom are merely carriers of this microorganism. H. pylori is shown to be detected more frequently in patients with diabetes mellitus (DM) than in the general population, which is accompanied by a significantly increased risk of developing H. pylori-associated diseases. In addition, eradication therapy shows a low efficiency for H. pylori infection in patients with DM. There is a relationship between the level of chronic hyperglycemia and a higher detection rate of H. pylori as well as a lower efficiency of eradication therapy in patients with DM. The exact mechanisms of these phenomena are unknown. The authors make a hypothesis that explains the relationship between chronic hyperglycemia and the increased detection rate of H. pylori, as well as the mechanisms contributing to the improved survival of this bacterium in patients with DM during eradication therapy.     

“Helicobacter pylori treatment guideline: An Indian perspective”: Letter to the editor

Treatment guidelines in many countries for Helicobacter pylori (H. pylori) may differ. Owing to the various characteristics of bacteria, clinical manifestations, resistance to antibiotics and recurrence rate, treatment regimens may change. In this letter, we would like to give an Indian perspective on H. pylori treatment guidelines.     

胃癌相关甲基化分型与幽门螺杆菌感染的探讨

目的 探讨基因甲基化分型与幽门螺杆菌感染在胃癌预后中的临床价值。方法 使用甲基化特异性PCR技术分析75例胃癌病人血清中的CpG岛甲基化分型(CIMP),同时分析了40例健康人血清作为对照。APC,WIF-1,RUNX-3,DLC-1,SFRP-1,DKK和E-cad作为研究基因。幽门螺杆菌感染由血清抗幽门螺杆菌G抗体试验和快速脲酶试验确定。结果 7个基因胃癌组织中甲基化的频率如下:APC 48%,WIF-1 57.33%,RUNX-3 56%,DLC-1 50.67%,SFRP-1 52%,DKK54.67%和E-cad 48%; 血清中甲基化的频率如下:APC 30.67%,WIF-1 34.67%,RUNX-3 37.33%,DLC-1 29.33%,SFRP-1 33.33%,DKK 32%和E-cad 26.67%。CIMP+(定义为≥3甲基化基因)与47例(62.67%)胃癌组织标本和44例(58.67%)GC血清样品相关联。CIMP+与非肿瘤黏膜组织和健康人的血清无关联。在75例胃癌中,有51例(68%)为幽门螺杆菌阳性,24例(32%)为幽门螺杆菌阴性。在51例幽门螺杆菌感染胃癌组织中,36例为CIMP+,15例为CIMP-。相反,在24例幽门螺杆菌阴性病例中,11例为CIMP+,13例为CIMP-。两组CIMP表达差异有统计学意义(χ2=4.27,P<0.05)。在51例幽门螺杆菌阳性胃癌血清样本中,34例为CIMP+,17例为CIMP-。24例未感染血清样本中,10例CIMP+,14例CIMP-。两组间差异有统计学意义(χ2= 4.21,P<0.05)。经过两年随访,发现HP+/CIMP+和HP+/CIMP-两组转移、复发率明显不同,HP+/CIMP+病人有转移、复发倾向(P<0.05); 生存率二者未见明显不同(P>0.05)。结论 HP+/CIMP+的病人比HP+/CIMP-更易转移和复发。     

Helicobacter pylori plays a key role in gastric adenocarcinoma induced by spasmolytic polypeptide-expressing metaplasia

Heliobacter pylori (H. pylori), a group 1 human gastric carcinogen, is significantly associated with chronic gastritis, gastric mucosal atrophy, and gastric cancer. Approximately 20% of patients infected with H. pylori develop precancerous lesions, among which metaplasia is the most critical. Except for intestinal metaplasia (IM), which is characterized by goblet cells appearing in the stomach glands, one type of mucous cell metaplasia, spasmolytic polypeptide-expressing metaplasia (SPEM), has attracted much attention. Epidemiological and clinicopathological studies suggest that SPEM may be more strongly linked to gastric adenocarcinoma than IM. SPEM, characterized by abnormal expression of trefoil factor 2, mucin 6, and Griffonia simplicifolia lectin II in the deep glands of the stomach, is caused by acute injury or inflammation. Although it is generally believed that the loss of parietal cells alone is a sufficient and direct cause of SPEM, further in-depth studies have revealed the critical role of immunosignals. There is controversy regarding whether SPEM cells originate from the transdifferentiation of mature chief cells or professional progenitors. SPEM plays a functional role in the repair of gastric epithelial injury. However, chronic inflammation and immune responses caused by H. pylori infection can induce further progression of SPEM to IM, dysplasia, and adenocarcinoma. SPEM cells upregulate the expression of whey acidic protein 4-disulfide core domain protein 2 and CD44 variant 9, which recruit M2 macrophages to the wound. Studies have revealed that interleukin-33, the most significantly upregulated cytokine in macrophages, promotes SPEM toward more advanced metaplasia. Overall, more effort is needed to reveal the specific mechanism of SPEM malignant progression driven by H. pylori infection.     

Application of polymerase chain reaction-based assays for rapid identification and antibiotic resistance screening of Helicobacter pylori in gastric biopsies

The benefits of using a multiplex detection polymerase chain reaction (PCR) assay for Helicobacter pylori speciation and 2 real-time probe hybridization assays determining clarithromycin and tetracycline susceptibilities in gastric biopsies from 171 dyspeptic patients were investigated. Overall, 70 of 71 H. pylori culture-positive biopsies were PCR positive. For the 100 culture-negative biopsies, PCR identified a further 29 H. pylori positives (17% overall) and presence of resistance markers for clarithromycin (20/28) and tetracycline (2/28). The results demonstrated that PCR testing was valuable in providing improved detection rates and antibiotic susceptibility information when H. pylori culture was unsuccessful.     

Suppression of Helicobacter pylori infection during intensive care stay: related to stress ulcer bleeding incidence?

Purpose: To assess the prevalence of active Helicobacter pylori infection in patients admitted to the intensive care unit, to determine the effect of selective gut decontamination on the persistence of this organism, and to explore the possible relationship between H. pylori infection and stress ulcer bleeding incidence. Materials and Methods: We determined in a prospective observational study of 300 consecutive, mechanically ventilated patients the activity of H. pylori infection and the incidence of stress ulcer–related upper gastrointestinal bleeding over time. H. pylori infection was detected by Laser-Assisted Ratio Analyzer (LARA)- ¹³C-urea breath test (Alimenterics, Inc., NJ) and serology. Stress ulcer prophylaxis was not prescribed. Endoscopy was performed in cases of upper gastrointestinal bleeding. Results: The prevalence of active H. pylori infection on admission was 38% as detected by urea breath test, and declined to 8% on the third day, and to 0% on the seventh day after admission as a result of antibiotic treatment. Stress ulcer–related upper gastrointestinal bleeding occurred in 1.0% (3 of 300) of the patients; none were infected with H. pylori on admission or at the time of bleeding. Conclusions: H. pylori infection monitored by LARA- ¹³C-urea breath test was rapidly suppressed during intensive care treatment, which can be explained by the routine use of antibiotics for gut decontamination.The low incidence of stress ulcer–related bleeding might be related to the prevention of H. pylori–associated stress lesions by effective suppression of this microorganism, but further studies are warranted to test this hypothesis. Copyright © 2002 by W.B. Saunders Company     

质子泵抑制剂大剂量二联与铋剂四联在幽门螺杆菌根除治疗中的疗效比较

目的 比较质子泵抑制剂大剂量二联与铋剂四联对幽门螺杆菌(Helicobacter pylori,H.pylori)的根除率和不良反应的发生率.方法 选择2021年1月至2021年8月就诊于河北省人民医院消化内科门诊的H.pylori阳性患者208例,随机分为试验组(质子泵抑制剂大剂量二联)和对照组(铋剂四联),其中试验...     

Susceptibility of Helicobacter pylori isolates to the antiadhesion activity of a high-molecular-weight constituent of cranberry

The sensitivity of a large number of antibiotic-resistant and nonresistant Helicobacter pylori isolates to the antiadhesion effect of a high-molecular-mass, nondialysable constituent of cranberry juice was tested. Confluent monolayers of gastric cell line in microtiter plate wells were exposed to bacterial suspensions prepared from 83 H. pylori isolates from antibiotic-treated and untreated patients in the presence and absence of the cranberry constituent. Urease assay was used to calculate the percentage of adhesion inhibition. In two thirds of the isolates, adhesion to the gastric cells was inhibited by 0.2 mg/mL of the nondialysable material. There was no relationship between the antiadhesion effect of the cranberry material and metronidazole resistance in isolates from either treated or untreated patients (N = 35). Only 13 isolates (16%) were resistant to both the nondialysable material and metronidazole, and 30 (36%) were resistant to the nondialysable material alone. There was no cross-resistance to the nondialysable material and metronidazole. These data suggest that a combination of antibiotics and a cranberry preparation may improve H. pylori eradication.     

Helicobacter pylori infection and asthma: Is there a direct or an inverse association? A meta-analysis

AIM: To analyze the consistency of a potential involvement of the bacterium infection in the asthma disease. METHODS: A systematic literature search of the terms “Helicobacter pylori” (H. pylori) associated to “asthma” using PubMed, Scopus and the Cochrane Library Central was performed. Reference lists from published articles were also employed. Titles of these publications and their abstracts were scanned in order to eliminate duplicates and irrelevant articles. The criteria of inclusion of the studies were: Original studies; the H. pylori diagnostic method has been declared; all ranges of age have been included in our study; a definitive diagnosis of asthma has been reported. RESULTS: We selected 14 articles in which the association between the two conditions was addressed. In 7 studies the prevalence of H. pylori infection in the asthma population and in the control population was made explicit. There was heterogeneity between the studies (Cohran’s Q = 0.02). The H. pylori infection in the asthma population resulted 33.6% (518 of 1542), while in the control population resulted 37.6% (2746 of 7310) (relative risk of H. pylori infection in the asthma population = 0.87, 95%CI: 0.72-1.05, P = 0.015, random effects model). Instead, considering the more virulent strains, the majority of studies showed an inverse relationship between the prevalence of H. pylori infection and asthma. CONCLUSION: In our meta-analysis the prevalence of H. pylori infection in the asthma population resulted not statistically significant lower than in control population (P = 0.15). Instead, considering the more virulent strains, the majority of studies showed an inverse relationship between the prevalence of H. pylori infection and asthma.     

Treatment strategies and preventive methods for drug-resistant Helicobacter pylori infection

The infection and drug resistance rates of Helicobacter pylori (H. pylori) are high and must be prevented and treated by better strategies. Based on recent research advances in this field as well as the results from our team and those on traditional Chinese medicine, we review the causes of drug resistance, and prevention and treatment strategies for drug-resistant H. pylori infection, with an aim to make suggestions for the development of new drugs, such as establishment of new target identification and screening systems, modification of existing drug structures, use of new technologies, application of natural products, and using a commercial compound library. This article may provide reference for eradication of drug-resistant H. pylori.     

Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion

CagA protein is a major virulence factor of Helicobacter pylori, which is delivered into gastric epithelial cells and elicits growth factor-like responses. Once within the cells, CagA is tyrosine phosphorylated by Src family kinases and targets host proteins required to induce the cell responses. We show that the phosphorylated CagA binds Crk adaptor proteins (Crk-II, Crk-I, and Crk-L) and that the interaction is important for the CagA-mediated host responses during H. pylori infection. H. pylori-induced scattering of gastric epithelial cells in culture was blocked by overexpression of dominant-negative Crk and by RNA interference-mediated knockdown of endogenous Crk. H. pylori infection of the gastric epithelium induced disruption of E-cadherin/catenin-containing adherens junctions, which was also dependent on CagA/Crk signaling. Furthermore, inhibition of the SoS1/H-Ras/Raf1, C3G/Rap1/B-Raf, or Dock180/Rac1/Wiskott-Aldrich syndrome protein family verprolin homologous protein pathway, all of which are involved downstream of Crk adaptors, greatly diminished the CagA-associated host responses. Thus, CagA targeting of Crk plays a central role in inducing the pleiotropic cell responses to H. pylori infection that cause several gastric diseases, including gastric cancer.     

Meta-analysis of single strain probiotics for the eradication of Helicobacter pylori and prevention of adverse events

AIM: To assess the efficacy and safety of single strain probiotics for the: (1) eradication of Helicobacter pylori (H. pylori); (2) prevention of adverse events; and (3) prevention of antibiotic-associated diarrhea associated with eradication therapy. METHODS: We searched PubMed (1960-2014), EMBASE (1974-2014), Cochrane Database of Systematic Reviews (1990-2014), and ISI Web of Science (2000-2014). Additionally, we conducted a grey literature search including contact with National Institutes of Health Clinical Trials Registry, abstracts from annual infectious disease and gastroenterology meetings, experts in the field and correspondence with authors. Randomized controlled trials of H. pylori positive adults or children treated with eradication therapy and assessing the adjunctive therapy with a single strain of probiotics were included. The primary outcomes were the rates of eradication of H. pylori and frequency of patients with adverse events or antibiotic-associated diarrhea. Outcomes were pooled using fixed or random-effects models to calculate the relative risk and corresponding 95%CI and weighted on study size. To explore possible explanations for heterogeneity, a priori subgroup analyses were conducted on daily probiotic dose, study population, and quality of the study. The overall quality of the evidence for each probiotic strain was assessed using the GRADE criteria. RESULTS: A total of 25 randomized controlled trials (28 treatment arms, with a total of 3769 participants) assessed one of six single probiotic strains as adjunctive treatments to standard eradication therapy. Only one probiotic strain significantly improved H. pylori eradication rates: Saccharomyces boulardii (S. boulardii) CNCM I-745 [pooled relative risks (pRR) = 1.11, 95%CI: 1.07-1.16]. Only one probiotic strain (S. boulardii CNCM I-745) significantly prevented any adverse events (pRR = 0.42, 95%CI: 0.28-0.62). Both S. boulardii CNCM I-745 and Lactobacillus rhamnosus GG significantly reduced antibiotic-associated diarrhea (pRR = 0.47, 95%CI: 0.37-0.60 and pRR = 0.29, 95%CI: 0.17-0.48, respectively) associated with H. pylori eradication therapy. Meta-regression of sub-groups did not detect significant differences by dose, adult vs pediatric, symptom status, or study quality, but did find significant differences by the strain of probiotic. Potential mild publication bias was found for antibiotic-associated diarrhea, but not for eradication or adverse event outcomes. Analysis of the study quality illuminated areas for improvement in future studies (use of placebos, study size calculations, attrition reasons and discussion of limitations and generalizability). CONCLUSION: The pooled evidence suggests that the adjunctive use of a few probiotic strains may improve H. pylori eradication rates and prevent the development of adverse events and antibiotic-associated diarrhea in those treated with standard eradication therapies. The type of probiotic strain was the most important factor in predicting efficacy.     

Association of CagA-positive infection with Helicobacter pylori antibodies of IgA class

cagA gene, the best known virulence factor of Helicobacter pylori, codes for an immunodominant CagA protein. In this study, CagA antibodies of the IgG class were measured by immunoblot or enzyme immunoassay in subjects with positive H. pylori serology, and the presence of CagA antibodies was compared with that of H. pylori antibodies of IgA and IgG classes. Serum samples were available for a total of 1,481 subjects, including gastroscopied patients with biopsy-verified H. pylori infection, smoking men with a normal or low serum pepsinogen I level indicating atrophic corpus gastritis, and subjects who later developed gastric cancer and their matched controls. CagA antibodies were significantly more prevalent among individuals with elevated H. pylori antibody titres of the IgA class than in those with IgG antibodies only, with the exception of a small subgroup of individuals who later developed gastric cancer. CagA-positive H. pylori strains seem to induce an immune response with a markedly higher frequency of IgA than what is found in inflammation caused by CagA-negative strains. The presence of serum IgA antibodies to H. pylori seems to indicate a higher risk for CagA-positive H. pylori infection and possibly more severe late sequelae of the disease.