Detection of Helicobacter pylori strain types and analysis of risk factors among subjects from Hainan Province, China.

OBJECTIVE: To explore the prevalence of type I and type II Helicobacter pylori infection and investigate risk factors in a population from Hainan Province in China. METHODS: Data came from a large, cross-sectional study conducted from August 2022 to April 2023 involving five cities of Hainan. Subjects with confirmed 14C-urea breath test (UBT) and positive serological assay were included. All subjects had a gastroscopy. According to presence or absence of CagA/VacA proteins, subjects were classified as either type I (present) or type II strains (absent). Gastroscopic findings and several socio-demographic factors were examined for correlation with antibody serotyping. RESULTS: In total, 410 subjects were investigated for H. pylori strain types. The overall prevalence of the highly virulent, type I H. pylori strain was 79% (324/410) and type II strain was 21% (86/410). There was a strong association between type I strain and peptic ulcer disease. Of several sociodemographic factors investigated, only smoking and data over baseline (DOB) values showed significant differences between type 1 and type II strains. Logistic regression analysis showed a lower risk of type I H. pylori infection in smokers compared with non-smokers, and a higher risk of H. pylori type I infection in subjects with medium and high data over baseline (DOB) values compared with subjects who had low DOB values. CONCLUSION: Highly virulent, type I H. pylori infections predominate in Hainan and the co-positivity of CagA and VacA antibodies are related to type I H. pylori infection. We found that Type I H. pylori was closely associated with peptic ulcer disease and the DOB values were generally high.

Causal relationships of Helicobacter pylori and related gastrointestinal diseases on Type 2 diabetes: Univariable and Multivariable Mendelian randomization.

BACKGROUND: Previous observational studies have demonstrated a connection between the risk of Type 2 diabetes mellitus (T2DM) and gastrointestinal problems brought on by Helicobacter pylori (H. pylori) infection. However, little is understood about how these factors impact on T2DM. METHOD: This study used data from the GWAS database on H. pylori antibodies, gastroduodenal ulcers, chronic gastritis, gastric cancer, T2DM and information on potential mediators: obesity, glycosylated hemoglobin (HbA1c) and blood glucose levels. Using univariate Mendelian randomization (MR) and multivariate MR (MVMR) analyses to evaluate the relationship between H. pylori and associated gastrointestinal diseases with the risk of developing of T2DM and explore the presence of mediators to ascertain the probable mechanisms. RESULTS: Genetic evidence suggests that H. pylori IgG antibody (P = 0.006, b = 0.0945, OR = 1.0995, 95% CI = 1.023-1.176), H. pylori GroEL antibody (P = 0.028, OR = 1.033, 95% CI = 1.004-1.064), gastroduodenal ulcers (P = 0.019, OR = 1.036, 95% CI = 1.006-1.068) and chronic gastritis (P = 0.005, OR = 1.042, 95% CI = 1.012-1.074) are all linked to an increased risk of T2DM, additionally, H. pylori IgG antibody is associated with obesity (P = 0.034, OR = 1.03, 95% CI = 1.002-1.055). The results of MVMR showed that the pathogenic relationship between H. pylori GroEL antibody and gastroduodenal ulcer in T2DM is mediated by blood glucose level and obesity, respectively. CONCLUSION: Our study found that H. pylori IgG antibody, H. pylori GroEL antibody, gastroduodenal ulcer and chronic gastritis are all related to t T2DM, and blood glucose level and obesity mediate the development of H. pylori GroEL antibody and gastroduodenal ulcer on T2DM, respectively. These findings may inform new prevention and intervention strategies for T2DM.

Helicobacter pylori Infection: A 40-Year Journey through Shifting the Paradigm to Transforming the Management.

BACKGROUND: Helicobacter pylori (H. pylori) was discovered 40 years ago and has set a milestone in human medicine. The discovery led to rejection of the dogma of the acidic stomach as a sterile organ and requested to rewrite the chapters on gastric pathophysiology and gastroduodenal diseases. SUMMARY: Over a period of 40 years following the discovery, more than 50,000 articles can be retrieved in PubMed as of today and illustrate the amount and the intensity of research around the role of this bacterium. H. pylori emerged as cause of chronic gastritis and principal cause of peptic ulcer disease (PUD). Eradication of H. pylori became standard of care in management in PUD. The importance of this was highlighted in 2005 with the Nobel Prize in Medicine awarded to Barry Marshall and Robin Warren. H. pylori became eventually recognized for its oncogenic potential in the stomach and as the main risk factor for gastric cancer development. KEY MESSAGES: H. pylori gastritis is defined as infectious disease and requires therapy in all infected individuals. Strategies of gastric cancer prevention and development of therapies to overcome the increasing antibiotic resistance are main targets in clinical research of today.

Infiltration to infection: key virulence players of Helicobacter pylori pathogenicity.

PURPOSE: This study aims to comprehensively review the multifaceted factors underlying the successful colonization and infection process of Helicobacter pylori (H. pylori), a prominent Gram-negative pathogen in humans. The focus is on elucidating the functions, mechanisms, genetic regulation, and potential cross-interactions of these elements. METHODS: Employing a literature review approach, this study examines the intricate interactions between H. pylori and its host. It delves into virulence factors like VacA, CagA, DupA, Urease, along with phase variable genes, such as babA, babC, hopZ, etc., giving insights about the bacterial perspective of the infection The association of these factors with the infection has also been added in the form of statistical data via Funnel and Forest plots, citing the potential of the virulence and also adding an aspect of geographical biasness to the virulence factors. The biochemical characteristics and clinical relevance of these factors and their effects on host cells are individually examined, both comprehensively and statistically. RESULTS: H. pylori is a Gram-negative, spiral bacterium that successfully colonises the stomach of more than half of the world's population, causing peptic ulcers, gastric cancer, MALT lymphoma, and other gastro-duodenal disorders. The clinical outcomes of H. pylori infection are influenced by a complex interplay between virulence factors and phase variable genes produced by the infecting strain and the host genetic background. A meta-analysis of the prevalence of all the major virulence factors has also been appended. CONCLUSION: This study illuminates the diverse elements contributing to H. pylori's colonization and infection. The interplay between virulence factors, phase variable genes, and host genetics determines the outcome of the infection. Despite biochemical insights into many factors, their comprehensive regulation remains an understudied area. By offering a panoramic view of these factors and their functions, this study enhances understanding of the bacterium's perspective, i.e. H. pylori's journey from infiltration to successful establishment within the host's stomach.

Factors associated with treatment failure, and possible applications of probiotic bacteria in the arsenal against Helicobacter pylori.

INTRODUCTION: Helicobacter pylori is a widespread helical Gram-negative bacterium, which causes a variety of stomach disorders, such as peptic ulcer, chronic atrophic gastritis, and gastric cancer. This microbe frequently colonizes the mucosal layer of the human stomach and survives in the inhospitable microenvironment, by adapting to this hostile milieu. AREAS COVERED: In this extensive review, we describe conventional antibiotic treatment regimens used against H. pylori including, empirical, tailored, and salvage therapies. Then, we present state-of-the-art information about reasons for treatment failure against H. pylori. Afterward, the latest advances in the use of probiotic bacteria against H. pylori infection are discussed. Finally, we propose a polymeric bio-platform to provide efficient delivery of probiotics for H. pylori infection. EXPERT OPINION: For effective probiotic delivery systems, it is necessary to avoid the early release of probiotics at the acidic stomach pH, to protect them against enzymes and antimicrobials, and precisely target H. pylori bacteria which have colonized the antrum area of the stomach (basic pH).

New CagL Amino Acid Polymorphism Patterns of Helicobacter pylori in Peptic Ulcer and Non-Ulcer Dyspepsia.

Background and Objectives: Helicobacter pylori infection is associated with chronic gastritis, ulcers, and gastric cancer. The H. pylori Type 4 secretion system (T4SS) translocates the CagA protein into host cells and plays an essential role in initiating gastric carcinogenesis. The CagL protein is a component of the T4SS. CagL amino acid polymorphisms are correlated with clinical outcomes. We aimed to study the association between CagL amino acid polymorphisms and peptic ulcer disease (PUD) and non-ulcer dyspepsia (NUD). Materials and Methods: A total of 99 patients (PUD, 46; NUD, 53) were enrolled and screened for H. pylori by qPCR from antrum biopsy samples. The amino acid polymorphisms of CagL were analyzed using DNA sequencing, followed by the MAFFT sequence alignment program to match the amino acid sequences. Results: Antrum biopsy samples from 70 out of 99 (70.7%) patients were found to be H. pylori DNA-positive. A positive band for cagL was detected in 42 out of 70 samples (PUD, 23; NUD, 19), and following this, these 42 samples were sequenced. In total, 27 different polymorphisms were determined. We determined three CagL amino acid polymorphism combinations, which were determined to be associated with PUD and NUD. Pattern 1 (K35/N122/V134/T175/R194/E210) was only detected in PUD patient samples and was related to a 1.35-fold risk (p = 0.02). Patterns 2 (V41/I134) and 3 (V41/K122/A171/I174) were found only in NUD patient samples and were linked to a 1.26-fold increased risk (p = 0.03). Conclusions: We observed three new patterns associated with PUD and NUD. Pattern 1 is related to PUD, and the other two patterns (Patterns 2 and 3) are related to NUD. The patterns that we identified include the remote polymorphisms of the CagL protein, which is a new approach. These patterns may help to understand the course of H. pylori infection.

[The history of the discovery of the Helicobacter pylori].

Helicobacter pylori is a spiral-shaped gram-negative bacterium that colonizes the stomach lining. The presence of a microorganism in humans was described more than a century ago, but from detection to recognition of its role in the etiology and pathogenesis of diseases of the stomach, researchers had to overcome a long path of criticism and mistrust. Coiled bacteria have been mentioned several times in the medical literature, but these bacteria were thought to be contaminants, and any evidence of the bacteria in the stomach was ignored by the medical community. The discovery of H. pylori led to a revolutionary rethinking of the mechanisms of development of a number of diseases: the role of bacteria in the development of chronic gastritis, peptic ulcer disease, stomach cancer and MALT lymphoma was proved. The principles of their prevention and treatment have changed. For this discovery in 2005, Barry Marshall and Robin Warren were awarded the Nobel Prize in Medicine and Physiology.

Benzimidazole derivatives: A versatile scaffold for drug development against Helicobacter pylori-related diseases.

Helicobacter pylori (H. pylori) is a microaerophilic gastric pathogen and a major contributor to chronic atrophic gastritis, peptic ulcer, and gastric malignancies. The increasing prevalence of H. pylori infection and its related diseases, such as gastric cancer (GC), motivates medicinal chemists to seek for more effective multi-targeting drugs to prevent and treat H. pylori-related clinical complications. Benzimidazole, a hetero-aromatic bicyclic ring compound, has claimed a prominent role in medicinal chemistry owing to its broad range of biological activities, including antibacterial, antiviral, antidiabetic, and anticancer activities. Studies highlight the promising therapeutic potential of benzimidazole derivatives in the treatment of H. pylori-related clinical complications such as gastric infection, gastritis, peptic ulcer, and GC. Accordingly, we here aimed to scrutinize the role of active molecules of benzimidazole derivatives as potential antibacterial, anti-urease, anti-inflammatory, anti-ulcerative, and anticancer agents, which are expected to find their ways to the clinical setting sooner or later. Due to the role of structural moieties in determining the biological behaviors of benzimidazole derivatives, we explored the structure-activity relationship (SAR) of these compounds to further expand the scope of design of and research on new drugs against H. pylori-related diseases.

Mapping microbiome-redox spectrum and evaluating Microbial-Redox Index in chronic gastritis.

Peptic ulcer disease (PUD) and chronic gastritis are prevalent in developing countries. The role of oxidative stress in the pathogenesis of gastrointestinal mucosal disorders is well recognized. In PUD, the gastric mucosa and its associated microbiome are subject to diet and stress-induced oxidative perturbations. Tissue redox potential (ORP) measurement can quantify oxidative stress, reflecting the balance between prooxidants and antioxidants. This study hypothesizes that the oxidative stress quantified by tissue ORP will be associated with characteristic changes in the mucosa-associated microbiome in PUD and gastritis. In addition, we propose using relative microbial abundance as a quantitative marker of mucosal health. Endoscopy was performed to obtain gastric mucosal biopsies from ten PUD and ten non-ulcer dyspepsia (NUD) patients. The tissue ORP was measured directly with a microelectrode using a biopsy specimen. A second specimen from an adjacent site was subjected to 16s rRNA gene sequencing. From the OTUs, the relative abundance of the microbial taxon in each of the samples was derived. We analyzed the genome of the predominant species for genes encoding the utilization of oxygen as an electron acceptor in respiration and for the presence of antioxidant defense mechanisms. The organisms were then grouped based on their established and inferred redox traits. Shannon diversity index and Species richness were calculated on rarefied data. The relative abundance of organisms that prefer high ORP over those that favor low ORP is conceived as the "Microbial Redox Index (MRI)," an indicator of mucosal health. In the gastric mucosa, aerobic species predominate and are more diverse than the anaerobes. The predominant aerobes are Helicobacter pylori and Sphingobacterium mizutaii. The abundance of these two species had an inverse correlation with the abundance of low ORP preferring anaerobes. Their relative abundance ratio (Microbial Redox Index) correlated with the tissue oxidation-reduction potential (ORP), a direct measure of oxidative stress. Correlation analysis also revealed that the abundance of all anaerobes inversely correlated with the dominant aerobic taxa. In addition, Shannon and Species richness diversity indices, the probable indicators of mucosal health, were negatively correlated with Microbial Redox Index. Using PUD as a prototype mucosal disease, this article describes a generalized approach to infer and quantify mucosal oxidative stress by analyzing the relative abundance of microorganisms that preferentially grow at the extremes of the tissue redox potential. This ratiometric Microbial Redox Index can also be assessed using simple qPCR without the need for sequencing. The approach described herein may be helpful as a widely applicable quantitative measure of mucosal health with prognostic and therapeutic implications.

Frequency of Helicobacter pylori Infection in Patients with Peptic Ulcer Referred to the Endoscopy Departments of Khorramabad City Hospitals, Iran, During 2013-2016.

BACKGROUND: The present study investigated the prevalence of Helicobacter pylori infection in peptic ulcer patients referred to the endoscopy departments in Khorramabad hospitals during 2013- 2016. METHODS: The early pool of the study included all patients who had been referred to the endoscopy department and whose endoscopic and pathology reports were available and complete. After recording endoscopic reports, 1224 peptic ulcer (gastric or duodenal ulcer) cases, in which biopsy assays were performed to examine the type of ulcer and the presence of Helicobacter pylori bacteria, were selected. Pathology reports were collected by referring to the pathology departments. The information in the pathology report, including demographic information, was included in a pre-designed questionnaire to match the endoscopic reports, the location of the pathology sample, and other details, including the presence or absence of Helicobacter pylori bacteria. Finally, the data were analyzed using SPSS, version 21. RESULTS: For all the 1224 patients studied, the mean age was 15.5 ± 17.5 years old. A total of 664 (54.2%) cases had gastric ulcers, 445 (36.4%) cases had duodenal ulcers, and 115 (9.4%) had both gastric and duodenal ulcers. Among gastric ulcer patients, 512 (65.7%) had a gastric ulcer in the antrum area, and 74.3% (579 patients) of the gastric ulcers were clean base type. CONCLUSION: The prevalence of infection was statistically significant in terms of the type, location, and number of peptic ulcers, including both gastric ulcer and duodenal ulcer.

Integrative Analysis of Deregulated miRNAs Reveals Candidate Molecular Mechanisms Linking H. pylori Infected Peptic Ulcer Disease with Periodontitis.

OBJECTIVE: Periodontitis is a highly prevalent oral infectious disease and has been increasingly associated with H. pylori infection, gastric inflammation, and gastric cancer but little is known about epigenetic machinery underlying this potentially bidirectional association. The present study is aimed at identifying key deregulated miRNA, their associated genes, signaling pathways, and compounds linking periodontitis with H. pylori-associated peptic ulcer disease. METHODS: miRNA expression datasets for periodontitis-affected and H. pylori-associated peptic ulcer disease-affected tissues were sought from the GEO database. Differentially expressed miRNA (DEmiRNAs) were identified and the overlapping, shared-DEmiRNA between both datasets were determined. Shared-DEmiRNA-target networks construction and functional analyses were constructed using miRNet 2.0, including shared-DEmiRNA-gene, shared-DEmiRNA-transcription factor (TF), and shared-DEmiRNA-compound networks. Functional enrichment analysis for shared DEmiRNA-gene and shared DEmiRNA-TF networks was performed using the KEGG, Reactome, and Geno Ontology (GO) pathways. RESULTS: 11 shared-DEmiRNAs were identified, among which 9 showed similar expression patterns in both diseases, and 7 were overexpressed. miRNA hsa-hsa-mir-155-5p and hsa-mir-29a-3p were top miRNA nodes in both gene and TF networks. The topmost candidate miRNA-deregulated genes were PTEN, CCND1, MDM2, TNRC6A, and SCD while topmost deregulated TFs included STAT3, HIF1A, EZH2, CEBPA, and RUNX1. Curcumin, 5-fluorouracil, and the gallotanin 1,2,6-Tri-O-galloyl-beta-D-glucopyranose emerged as the most relevant linkage compound targets. Functional analyses revealed multiple cancer-associated pathways, PI3K pathways, kinase binding, and transcription factor binding among as enriched by the network-associated genes and TFs. CONCLUSION: Integrative analysis of deregulated miRNAs revealed candidate molecular mechanisms comprising of top miRNA, their gene, and TF targets linking H. pylori-infected peptic ulcer disease with periodontitis and highlighted compounds targeting both diseases. These findings provide basis for directing future experimental research.

Clinical relevance of virulence genes in Helicobacter pylori isolates recovered from adult dyspeptic patients in Turkey.

PURPOSE: Bacterial virulence factors play a major role in the pathogenesis of Helicobacter pylori infection. The aims of this study were to evaluate virulence genes in H. pylori isolates and to compare the presence of these genes and associated clinical pathologies. METHODS: A total of 148 H. pylori isolates, recovered from adult dyspeptic patients, were used. The patients, from whom the isolates were obtained, were assigned to two groups by their endoscopic findings, which manifested as chronic gastritis or peptic ulcer. The presence of gastric atrophy and intestinal metaplasia was recorded for each patient, based on histopathological examination. Analyses of the virulence genes were performed by the polymerase chain reaction technique. RESULTS: The patients had a mean age of 47 â€‹± â€‹15 years and 86 (58%) of them were female. Based on endoscopic examination, 103 (69.6%) patients were diagnosed with chronic gastritis and 45 (30.4%) with peptic ulcer. Histopathological examination revealed intestinal metaplasia in 30 (20%) patients and gastric atrophy in 12 (8%) patients. The prevalence rates of cagA, cagE, iceA1, iceA2, and babA2 were determined to be 87%, 74%, 58%, 26%, and 95%, respectively. The most prevalent vacA alleles were s1/s1a (82%/97%) and the least prevalent allele was s2 (20%). A new vacA genotype (s1as1bs1c) was detected, for the first time, in 18 (12%) isolates. No significant difference was found between the patient groups with chronic gastritis and peptic ulcer for the prevalences of the virulence genes (p â€‹> â€‹0.05). Furthermore, intestinal metaplasia and gastric atrophy showed no significant correlation with the virulence genes (p â€‹> â€‹0.05). CONCLUSIONS: It is thoughted that H. pylori isolates with predominant cagA, cagE, VacA (s1, s1a), and babA2 virulence genes are associated with gastroduodenal diseases. However, there is no correlation between gastric premalignant lesions and virulence genes.

Selective Inhibition of Helicobacter pylori Carbonic Anhydrases by Carvacrol and Thymol Could Impair Biofilm Production and the Release of Outer Membrane Vesicles.

Helicobacter pylori, a Gram-negative neutrophilic pathogen, is the cause of chronic gastritis, peptic ulcers, and gastric cancer in humans. Current therapeutic regimens suffer from an emerging bacterial resistance rate and poor patience compliance. To improve the discovery of compounds targeting bacterial alternative enzymes or essential pathways such as carbonic anhydrases (CAs), we assessed the anti-H. pylori activity of thymol and carvacrol in terms of CA inhibition, isoform selectivity, growth impairment, biofilm production, and release of associated outer membrane vesicles-eDNA. The microbiological results were correlated by the evaluation in vitro of H. pylori CA inhibition, in silico analysis of the structural requirements to display such isoform selectivity, and the assessment of their limited toxicity against three probiotic species with respect to amoxicillin. Carvacrol and thymol could thus be considered as new lead compounds as alternative H. pylori CA inhibitors or to be used in association with current drugs for the management of H. pylori infection and limiting the spread of antibiotic resistance.

Heterogeneity of Helicobacter pylori bab genotypes and their association with clinical outcomes in Korean gastroduodenal patients.

In this study, we aimed to investigate the prevalence of bab genes (babA, babB, babC) at their three loci (loci A, B, and C) in Helicobacter pylori strains from varied clinical manifestations of Korean gastroduodenal patients. The overall prevalence of H. pylori Korean strains positive for babA and babB was 91.1% and 92.2%, respectively, but all strains were negative for bab C. H. pylori strains with two loci occupied (loci A and B) were the most prevalent in Korean patients (85.6%), compared to one locus occupied (14.4%) (locus A or B). Twelve bab genotypes were detected, additionally, the distribution of three bab genotypes was significantly associated with different clinical outcomes among Korean patients. The genotypes babA/babB/- and babA/babA+babB/- were significantly associated with peptic ulcer disease (PUD) (63.3%) and gastritis (GT) (33.3%) patients, respectively. In addition, we found that the babA+babB/babA+babB/- genotype was significantly associated with gastric cancer (GC) (36.7%) as compared to GT (6.7%) or PUD (6.7%) (p<0.05) patients. This study provided evidence that the bab genotypes in H. pylori Korean strains were highly variable. Interestingly, three patterns of bab genotypes were significantly different among patients with different clinical outcomes in the population at high-risk for GC.

Functional Dyspepsia, Peptic Ulcer, and Helicobacter pylori Infection in a Rural Community of South Asia: An Endoscopy-Assisted Household Survey.

INTRODUCTION: Functional dyspepsia (FD), although commoner than organic dyspepsia (OD) in-hospital studies, community data, particularly from rural areas, are lacking. We performed a rural community study in Bangladesh with the primary aims to evaluate (i) the prevalence of uninvestigated dyspepsia (UD), FD, and OD and (ii) the risk factors for UD. METHODS: This house-to-house survey was performed using a translated-validated enhanced Asian Rome III questionnaire and endoscopy with Helicobacter pylori tests, including genotyping. RESULTS: Of 3,351/3,559 responders ([94.15%], age 40.41 ± 16.05 years, female 1924 [57.4%]), 547 (16.3%) had UD (female 346 [18%] vs male 201 [14%]; P = 0.002); 201 (6%), 88 (2.6%), and 258 (7.7%) had postprandial distress (PDS), epigastric pain syndromes (EPS) and PDS-EPS overlap, respectively. On multivariate analysis, age >50 years (adjusted odds ratio [AOR] 1.34 [1.07-1.68]), female sex (AOR 1.42 [1.17-1.74]), being married (AOR 1.57 [1.21-2.07]), lower family income (AOR 1.79 [1.43-2.26]), nonsteroidal anti-inflammatory drug use (AOR 7.05 [2.11-23.55]), previous acute gastroenteritis (AOR 5.42 [1.83-16]), and psychological distress (AOR 5.02 [2.87-8.76]) were risk factors for UD. Of 346/547 (63.25%) undergoing endoscopy, 232 (67.05%) and 114 (32.95%) had FD and OD (peptic ulcers [PU] 99 [28.61%] and erosive esophagitis 13 [3.76%]). About 53% of FD subjects had EPS-PDS overlap, 32% had PDS, and only 15% had EPS. H. pylori was detected in 266/342 (78%) dyspeptics (FD 173/230 [75.2%], vs OD 92/114 [82.1%], P = 0.169). DISCUSSION: Sixteen percent, 11% and 5% of rural Bangladeshi Asian adults had UD, FD, and PU, respectively. One-third of UD subjects had OD, mostly PU.JOURNAL/cltg/04.03/01720094-202104000-00016/inline-graphic1/v/2021-04-15T161418Z/r/image-tiff.

A Mouse Model of Helicobacter pylori Infection.

Infection with Helicobacter pylori (H. pylori) is of great distress because of its vital role in the pathogenesis of chronic gastritis, peptic ulcers, and in the multi-step carcinogenic process of gastric cancer. The increasing antibiotic resistance pattern of H. pylori worldwide has prompted the World Health Organization to put this organism in the priority pathogens list. To study the disease biology, evaluation of drugs, treatment outcome and to come up with probable vaccination strategies, competent animal models that reproduce the signature of human infection are essential. Initial reports about animal colonization with H. pylori have shown significant heterogeneity, to such an extent that Barry Marshall, Nobel laureate for the discovery of H. pylori , infected himself with the bacterium to show its involvement in acute gastric illness. A paradigm-shift discovery of the H. pylori mouse-adapted strain SS1 has opened the avenues of research regarding the organism and its pathogenicity. Although the mouse model of H. pylori infection is being utilized all over the world, there are certain issues that need awareness and specific information to achieve successful, consistent colonization with symptoms resembling human. This chapter details an established and reliable protocol for the development of a competent mouse model for H. pylori infection leading to various gastro-intestinal diseases.

Risk of head and neck cancer in patients with peptic ulcers and the effect of Helicobacter pylori treatment.

It remained inconclusive whether patients with peptic ulcer disease had a higher risk of head and neck cancer (HNC). Therefore, we enrolled 109,360 patients with peptic ulcer disease and matched for age and sex with 218,720 controls from the Taiwan National Health Insurance Research Database between January 1, 1997 and December 31, 2013.The HNC incidence rate was 1.33-fold higher in the peptic ulcer group than in the control group (7.52 vs. 5.68 per 100,00 person-years; crude relative risk: 1.33; 95% confidence interval [CI]: 1.08-1.63) after > 6 years of follow-up. However, in the peptic ulcer subgroup with H. pylori treatment, HNC risk was not significantly different from that of the control group (crude relative risk: 1.12; 95% CI: 0.86-1.46). Moreover, the population with peptic ulcers had the highest risk of laryngeal and hypopharyngeal cancer (adjusted HR: 2.27 [95% CI: 1.16-4.44] and 2.00 [95% CI, 1.13-3.55]), respectively. This observational study suggested that peptic ulcer disease is associated with an increased incidence of laryngeal and hypopharyngeal cancer and H. pylori treatment may have a role in preventing HNC in patients with peptic ulcer disease.

A standardized protocol improves testing rates for Helicobacter Pylori among inpatients with peptic ulcer disease.

BACKGROUND: Despite a strong link between Helicobacter Pylori infection and peptic ulcer disease (PUD), rates of testing for H. Pylori in hospitalized patients with PUD remain largely unexplored. We aimed to determine H. Pylori testing practices at our institution among inpatients with PUD, and to implement a protocol to improve testing rates. MATERIALS AND METHODS: In this quality improvement initiative, baseline H. Pylori testing practices were determined by analysis of historical data on 100 subsequent inpatients with PUD from January 2016 to June 2017 at a tertiary care hospital undergoing esophagogastroduodenoscopy (EGD). Subsequently, a division-wide testing protocol was implemented, and data were analyzed from 43 consecutive inpatients with PUD from October 2019-March 2020 to determine the protocol's effects. RESULTS: The analysis of baseline testing practices showed a 57% testing rate for H. Pylori. Gastric biopsies were less likely to be performed during EGDs done outside the endoscopy unit (5.9% vs 32.7%, P = 0.001), outside of usual business hours (6.7% vs 24.3%, P = 0.04), and in cases where endoscopic therapy was administered (6% vs 32%, P = 0.02). After implementation of the new division-wide testing protocol, testing rates increased to 93% (P < 0.001). CONCLUSIONS: Low baseline inpatient testing for H. Pylori represents a missed opportunity to test a substantial number of high-risk patients with PUD. Implementation of a conceptually simple protocol aimed at increasing rates of gastric biopsy significantly improved testing rates in a prospective follow-up. Widespread standardization of H. Pylori testing for inpatients with PUD may improve important patient outcomes related to complicated PUD.

Increased Risk of Severe Gastric Symptoms by Virulence Factors vacAs1c, alpA, babA2, and hopZ in Helicobacter pylori Infection.

Two virulence factors of Helicobacter pylori, cagA and vacA, have been known to play a role in the development of severe gastric symptoms. However, they are not always associated with peptic ulcer or gastric cancer. To predict the disease outcome more accurately, it is necessary to understand the risk of severe symptoms linked to other virulence factors. Several other virulence factors of H. pylori have also been reported to be associated with disease outcomes, although there are many controversial descriptions. H. pylori isolates from Koreans may be useful in evaluating the relevance of other virulence factors to clinical symptoms of gastric diseases because the majority of Koreans are infected by toxigenic strains of H. pylori bearing cagA and vacA. In this study, a total of 116 H. pylori strains from Korean patients with chronic gastritis, peptic ulcers, and gastric cancers were genotyped. The presence of virulence factors vacAs1c, alpA, babA2, hopZ, and the extremely strong vacuolating toxin was found to contribute significantly to the development of severe gastric symptoms. The genotype combination vacAs1c/alpA/babA2 was the most predictable determinant for the development of severe symptoms, and the presence of babA2 was found to be the most critical factor. This study provides important information on the virulence factors that contribute to the development of severe gastric symptoms and will assist in predicting clinical disease outcomes due to H. pylori infection.

Contrasting association of Helicobacter pylori oipA genotype with risk of peptic ulceration and gastric cancer.

Helicobacter pylori OipA (outer inflammatory protein A) is an outer membrane protein that involves in the binding and colonization of the bacterium in the stomach. The oipA status is associated with the risk of peptic ulcerations (PUs) and gastric cancer (GC) diseases. However, the association trend with PUs compared to GC is often different and highly challenging. We therefore aimed to determine the presence of this genotype in Iranian strains and assess its association with the risk of PUs and GC in a larger number of samples. A total of 319 strains were obtained from 172 patients with non-atrophic gastritis (NAG), 52 with PUs and 95 with GC. The prevalence of the oipA+vs. oipA- genotype was 67.7% (216/319). The total frequency of the oipA+vs. oipA- genotypes in NAG, PUs, GC, non-peptic ulceration (including NAG and GC), and non-tumor (including NAG and PUs) groups was 121/172 (70.3%), 50/52 (96.2%), 45/95 (47.4%), 166/267 (62.2%), and 171/224 (76.3%), respectively. In multiple logistic regression analysis, the oipA+vs. oipA- genotype showed a strong direct association with PUs; the ORadj (95% CI) was 18.751 (4.421-79.531), (p = 0.00007). In contrast, it had a significant reverse association with GC; the ORadj (95% CI) was 0.330 (0.179-0.607), (p = 0.00036). In the present study, we interestingly found a contrasting association of the H. pylori oipA genotype with the risk of PUs and GC in Iran. Therefore, the contrasting effect of this genotype may emphasize its independent role in predicting clinical outcomes.