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.     

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.     

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 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.     

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.     

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.     

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.     

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.     

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 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.     

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     

含呋喃唑酮四联方案根除幽门螺杆菌引发严重不良反应1例

目的 探讨呋喃唑酮在幽门螺杆菌(Helicobacter pylori,Hp)根除过程中严重不良反应的发生情况及可能的影响因素。方法 回顾性收集2020年1月至2020年12月就诊于山西医科大学附属第一医院的1例在Hp根除过程中发生严重不良反应的病例资料,以“幽门螺杆菌”、“不良反应”、“呋喃唑酮”、“Helicobacter pylori”为关键词,搜索中国知网、万方数据知识服务平台以及PubMed数据库进行检索,分析呋喃唑酮在根除Hp过程中可能出现的不良反应及应对措施。结果 呋喃唑酮在根除Hp过程中可以导致肝功能异常、过敏性休克,而肠道细菌感染可能为引发这一不良反应的因素。结论 呋喃唑酮在根除Hp过程中可以导致双硫仑样反应、中毒性神经精神症状、高血压危象、肝功能异常、中毒性表皮坏死松解症等严重不良反应,超剂量用药、合并基础疾病、肠道细菌感染是诱发不良反应的潜在因素。临床医师应根据呋喃唑酮最新说明书,规范临床用药。     

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.     

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.     

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.     

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.     

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...     

Gastric mucosal immunity induced by H. pylori infection

H. pylori infection induces various humoral and cellular immunities in gastric mucosa. Some reports indicate predominant CD4+ cells infiltrate in H. pylori infected gastric mucosa, and these cells express the T helper 1 phenotype. Local humoral immunity is also induced. Gastric plasma cells produce anti-H. pylori antibodies, however, their protective immunity is not enough to eradicate bacteria in human. We found heat shock protein 60 kDa (hsp60) may be closely associated with pathogenesis in MALT lymphoma. IgG1 antibodies to hsp60 were significantly correlated with the antibodies to H. pylori whole cell in patients with MALT lymphoma. CD40-CD40L dependent B cell proliferation was induced by cytokine and/or hsp60 stimulations in those patients. Cytotoxicity of gastric epithelial cells which is associated with host immunity induced by H. pylori infection is still unclear. We found that lymphocytes from patients with peptic ulcer showed cytotoxicity to gastric cell line HGC-27 in vitro. Cytotoxicity was enhanced by cytokine stimulus to T-lymphocytes and by heat stress and/or patients' antibodies treatment of HGC-27 cells. The pathogenicity of H. pylori may involve not only bacterial virulence factor but also host immunity. Studies of mucosal local immunity will help explain the mechanisms of H. pylori induced gastrodoudenal diseases.     

Regulatory roles of extracellular vesicles in immune responses against Mycobacterium tuberculosis infection

Extracellular vesicles (EVs) are cystic vesicles naturally released by most mammalian cells and bacteria. EV contents include proteins, lipids, and nucleic acids. EVs can act as messengers to transmit a variety of molecules to recipient cells and thus play important regulatory roles in intercellular signal transduction. EVs, released by either a host cell or a pathogen, can carry pathogen-associated antigens and thus act as modulators of immune responses. EVs derived from Mycobacterium tuberculosis (Mtb)-infected cells can regulate the innate immune response through various pathways, such as regulating the release of inflammatory cytokines. In addition, EVs can mediate antigen presentation and regulate the adaptive immune response by transmitting immunoregulatory molecules to T helper cells. In this review, we summarize the regulatory roles of EVs in the immune response against Mtb.