Search

Background: Helicobacter pylori (H. pylori) is an established gastric carcinogen, also associated with an increased risk of colorectal cancer. Therefore, we suspected that H. pylori eradication lowers the risk of colorectal cancer., Material and Methods: We assessed if H. pylori eradication therapy is associated with a reduced risk of colorectal adenocarcinoma in a population-based nationwide cohort study. This study included all Swedish adults with at least one recorded H. pylori eradication episode between July 2005 and December 2012, based on the high-quality Swedish health registries. Colorectal adenocarcinoma risks were compared to the Swedish background population, presented as standardized incidence ratios (SIRs) and 95% confidence intervals (CIs), accounting for age, sex, calendar period, tumor location (left or right sided), stage, and number of eradication episodes, from 1 year after eradication and onward., Results: Among 80,381 individuals receiving H. pylori eradication therapy (average follow-up 4.1 years), 282 were diagnosed with colorectal cancer (97.2% adenocarcinoma). Overall, H. pylori eradication was associated with an elevated risk of colorectal adenocarcinoma (SIR 1.27, 95% CI: 1.12-1.43). The colorectal adenocarcinoma risk was increased 1-2 years after eradication (SIR 1.42, 95% CI: 1.17-1.72), then decreased 2-4 years (SIR 0.80, 95% CI: 0.65-0.98) and 4-6 years (SIR 0.76, 95% CI: 0.57-0.99), yet not ≥ 6 years (SIR 1.36, 95% CI: 0.78-2.21) after eradication compared to the general population. Overall, right-sided (SIR 1.47, 95% CI: 1.21-1.76) and left-sided (SIR 1.35, 95% CI: 1.09-1.67) colon adenocarcinomas risks were higher among eradicated individuals than the general population., Conclusion: H. pylori eradication was not associated with a clear and consistent reduction of colorectal cancer in our Swedish cohort., (© 2024 The Author(s). Helicobacter published by John Wiley & Sons Ltd.)

Background: Helicobacter pylori (H. pylori) is associated with lower risks of Barrett's esophagus and esophageal adenocarcinoma, but whether H. pylori eradication increases the risk of these conditions is unknown. This study aimed to test the hypothesis that H. pylori eradication leads to gradually increased risks of Barrett's esophagus and esophageal adenocarcinoma over time, while esophageal squamous cell carcinoma was assessed for comparison reasons., Material and Methods: This Swedish nationwide, population-based cohort study in 2005-2012 used data from the Swedish Prescribed Drug Registry to assess eradication treatment for H. pylori. Barrett's esophagus was identified from the Swedish Patient Registry, and esophageal adenocarcinoma and squamous cell carcinoma from the Swedish Cancer Registry. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by dividing the observed risk in the H. pylori eradication treatment cohort by the expected risk derived from the Swedish population of the same age, sex, and calendar period., Results: The cohort included 81 919 patients having had eradication treatment. For Barrett's esophagus (n = 178), the overall SIR was increased (SIR 3.67, 95% CI 3.15-4.25), but the SIRs slightly decreased over time after eradication treatment. For esophageal adenocarcinoma (n = 11), the overall SIR was 1.26 (95% CI 0.62-2.26), and the SIRs did not increase over time. The SIRs of esophageal squamous cell carcinoma (n = 10) were not influenced by eradication treatment., Conclusions: This study did not provide any evidence of an increasing risk of Barrett's esophagus or esophageal adenocarcinoma (or esophageal squamous cell carcinoma) over time after eradication treatment for H. pylori., (© 2020 The Authors. Helicobacter published by John Wiley & Sons Ltd.)

Background: The aim of this study was to produce a recombinant version of the highly antigenic Helicobacter pylori TonB (iron-dependent siderophore transporter protein HP1341) in transgenic plants as a candidate oral vaccine antigen., Materials and Methods: Using Agrobacterium-mediated gene transfer, we introduced three different constructs of the tonB gene into the genome of the model plant Arabidopsis thaliana. We investigated transgene insertion by PCR, produced TonB antibodies for analysis of the production of the recombinant protein in plants, verified the identity of the protein produced by mass spectrometry analysis, and analyzed the number of genetic inserts in the plants by Southern blotting., Results: Three different constructs of the expression cassette (full-length tonB, tonB truncated in the 5' end removing the codons for a transmembrane helix, and the latter construct with codons for the endoplasmic reticulum SEKDEL retention signal added to the 3' end) were used to find the most effective way to express the TonB antigen. Production of TonB protein was detected in plants transformed with each of the constructs, confirmed by both Western blotting and mass spectrometry analysis. No considerable differences in protein expression from the three different constructs were observed. The protein concentration in the plants was at least 0.05% of the total soluble proteins., Conclusions: The Helicobacter pylori TonB protein can be produced in Arabidopsis thaliana plants in a form that is recognizable by rabbit anti-TonB antiserum. These TonB-expressing plants are highly suitable for animal studies of oral administration as a route for immunization against Helicobacter infections., (© 2010 Blackwell Publishing Ltd.)

Background: A remarkable variety of restriction-modification (R-M) systems is found in Helicobacter pylori. Since they encompass a large portion of the strain-specific H. pylori genes and therefore contribute to genetic variability, they are suggested to have an impact on disease outcome. Type I R-M systems comprise three different subunits and are the most complex of the three types of R-M systems., Aims: We investigated the genetic diversity and distribution of type I R-M systems in clinical isolates of H. pylori., Material and Methods: Sixty-one H. pylori isolates from a Swedish hospital based case-control study and 6 H. pylori isolates of a Swedish population-based study were analyzed using polymerase chain reaction for the presence of the three R-M systems' subunits. Representative gene variants were sequenced., Results: Although the hsdM and hsdR genes appeared conserved in our clinical H. pylori isolates, the sequences of the hsdS loci were highly variable. Despite their sequence diversity, the genes per se were present at high frequencies. We identified a number of novel allelic hsdS variants, which are distinct from corresponding hsdS loci in the sequenced H. pylori strains 26695, J99 and HPAG1. In analyses of paired H. pylori isolates, obtained from the same individuals with a 4-year interval, we observed genetic modifications of hsdS genes in patients with atrophic gastric mucosa., Discussion: We propose that the genetic variability of hsdS genes in a bacterial population will give rise to new specificities of these enzymes, which might lead to adaptation to an ever-changing gastric environment.

Background and Aim: Antimicrobial resistance in Helicobacter pylori is a growing problem and has become an important factor leading to eradication failure. Information on antimicrobial susceptibility is important for selection of an optimum treatment regimen. The resistance rate in a random population has not been studied previously., Methods: A random Swedish population sample (n = 3000, age 20-1 years) was surveyed using a mailed validated questionnaire assessing gastrointestinal symptoms (response rate of 74%). One-third of the responders was invited, in random order, and accepted an esophagogastroduodenoscopy with biopsies for H. pylori culture and histology. Subjects were not treated for their H. pylori infection but a minimum inhibitory concentration of metronidazole, clarithromycin, amoxicillin, and tetracycline for the H. pylori isolates (n = 333) was determined by agar dilution. Prescribed antibiotic in the area was recorded., Results: Irrespective of symptomatology, 16.2% of the isolated H. pylori strains were resistant to metronidazole, 1.5% to clarithromycin, 0% to amoxicillin, and 0.3% to tetracycline. The antibiotic consumption was low from an international perspective., Conclusion: The resistance to the antibiotics was lower than expected from patient sample studies, especially for clarithromycin, most probably due to a restrictive prescription policy in the area. Introduction of a test-and-treat strategy in Sweden would only marginally affect the usage of clarithromycin.

Background: Infection with Helicobacter pylori is associated with an increased risk of gastric cancer. Several studies have indicated that the association differs with strain type. We aimed to find out if infection with strains lacking the virulence factor CagA is linked to gastric cancer risk., Materials and Methods: In a hospital-based case-control study, we collected sera from 100 case patients with a newly diagnosed gastric adenocarcinoma and 96 control patients with diseases unrelated to H. pylori status. Antibodies to H. pylori were analyzed by enzyme-linked immunosorbent assay (ELISA), and antibodies to CagA were detected by immunoblot. Logistic regression was used to obtain odds ratios (ORs) as estimates of relative risk, adjusted for potential confounding., Results: Among the case patients, 81% were ELISA positive and 86% had antibodies to CagA. The corresponding numbers among the controls were 58% and 55%, respectively. ELISA positivity was associated with an increased risk of gastric adenocarcinoma compared to ELISA negativity (OR for gastric cancer regardless of site 3.9, 95% CI 1.9-8.2). The OR was 7.4 (95% CI 3.3-16.6) for CagA-positive relative to CagA-negative subjects. Among ELISA-positive subjects the presence of CagA antibodies increased the risk 3.6 times (95% CI 1.2-11.1). ELISA-positive CagA-negative infections were associated with a fourfold increased risk (OR = 4.2, 95% CI 1.0-17.0) compared to no infection (ELISA-negative and CagA-negative)., Conclusions: Although patients with antibodies to CagA have the greatest risk of developing gastric cancer, those with CagA-negative infections run a significantly greater risk than uninfected persons.

Background: Genetic information is becoming increasingly important in diagnosis and prognosis of infectious diseases. In this study we investigated the possibility of using a single technology, the Pyrosequencing trade mark technology (Biotage AB, Uppsala, Sweden), to gather several kinds of important genetic information from the human pathogen Helicobacter pylori, as well as from the carrier of the H. pylori infection., Materials and Methods: DNA from 87 clinical isolates of H. pylori, 50 isolates from H. pylori-infected transgenic mice and nine gastric biopsies from H. pylori-infected patients was analyzed for targets in the 16S rRNA, 23S rRNA and cytotoxin associated gene A (cagA) genes to determine species identity, clarithromycin susceptibility and virulence level, respectively. In addition, three single nucleotide polymorphisms in the human interleukin-1B (IL-1B) gene, reported to affect the risk of developing gastric cancer, were analyzed in the gastric biopsy samples., Results: All DNA targets were processed and analyzed in parallel, enabling convenient genetic characterization of both pathogen and host. All genotypes were easily and accurately assigned. In the 16S rRNA analysis, 99.83% of the bases were correctly called., Conclusions: We conclude that genetic analysis using Pyrosequencing trade mark technology was nonlaborious, and gave highly accurate data for different kinds of target. We therefore believe that this technology has the potential to complement or in the future substitute the time-consuming traditional microbial identification and typing methods, as well as enabling rapid typing of relevant host genetic markers.

Background and Objectives: Intracellular location of Helicobacter pylori in human gastric epithelial cells has been observed in biopsies. Whether this reflects an ability to invade host cells and establish an intracellular niche remains to be determined., Methods: The interactions between a clinical isolate of H. pylori and primary cell cultures from human gastric epithelium or the human epithelial cell line HEp-2 were monitored using time-lapse photography. This technique allows studies of the dynamics of host-microbial interactions., Results: H. pylori cells readily approached and established close contacts with epithelial cells followed by uptake of the bacteria into the cellular cytoplasm. Entry into epithelial cells was achieved through an active process of bacterial motility and penetration of the cell membranes. In conventional invasion assays using HEp-2 cells, an increased internalization in a strain producing the vacuolating cytotoxin was observed, compared to the isogenic VacA knockout mutant., Conclusion: Invasion of gastric epithelium represents a hitherto unappreciated trait of H. pylori that could contribute to the bacterium's ability to establish persistent infection that evades the mucosal immune defense and sometimes also antimicrobial therapy. A small number of bacterial cells with a transient intracellular habitat could serve as a seeder population, providing a backup for a constantly challenged and fluctuating luminal population.

Background: During the conversion from the bacillary into the coccoid form, Helicobacter pylori organisms are known to change extensively. The aim of this study was to determine some of the changes that occur regarding morphology, intracellular composition and surface properties during the aging of bacteria in vitro., Materials and Methods: H. pylori from agar plate cultures of different ages was used in this study. The intracellular composition of the two morphological forms of the bacteria was tested by density centrifugation, DNA extraction and quantitative OD, mRNA and ATP measurements. Immunoblotting was used to observe changes in secreted/superficial protein patterns, and hydrophobicity measurements were used to observe changes in surface properties., Results: All bacillary H. pylori organisms changed morphology gradually over 10 days of culture. Rods had a higher density than cocci; bacteria stored in PBS had the highest density and bacteria stored in water had the lowest. The quantitative DNA, RNA and ATP content were reduced in the aging bacteria. Fewer immunogenic proteins were expressed, and an increased surface hydrophobicity was observed in the older cultures., Conclusion: This study highlights several aspects of H. pylori aging in vitro and shows some of the differences that exist between bacillary and coccoid forms. This information is important for understanding the transmission and survival of H. pylori outside the human host, as the degradative changes in the intracellular composition and the surface properties shown here point to dead bacteria, and not to a viable but nonculturable form.

Background: This double-blind, randomized study evaluated the efficacy of dual and triple therapies including ranitidine for treatment of Helicobacter pylori infection., Materials and Methods: Dyspeptic patients (n = 105) with a positive rapid urease test formed the intention-to-treat population (ITT). All patients were assigned to 14 days treatment with ranitidine 300 mg b.i.d and clarithromycin 750 mg b.i.d. Group A (n = 53) also received a placebo twice daily, while group B (n = 52) received lymecycline 300 mg b.i.d. Treatment with ranitidine, 150 mg b.i.d, was continued for an additional 30 days. H. pylori infection was verified by culture. Twelve weeks after antibiotic treatment, H. pylori status was investigated by culture and 14C-urea breath test (UBT). The per-protocol (PP) group consisted of 73 patients (A, n = 38; B, n = 35)., Results: Cure rates were 87% (95% C.I. = 72% to 94%) vs. 72% (95% C.I. = 58% to 83%) in the ITT-group and 89% (95% C.I. = 73% to 97%) vs. 87% (95% C.I. = 72% to 96%) in the PP-population (culture and UBT) when triple and dual therapies were compared. In all patients who were not cured, clarithromycin resistance of H. pylori was acquired. Side effects were experienced by 54% of patients., Conclusions: The difference in efficacy between the two treatment regimens was not significant. However, the cure rates in this study are comparable to combination treatments with omeprazole. Treatment failures were due to acquired clarithromycin resistance.

Background: We used egg passage of bacteria stored in water to evaluate the culturability of the coccoid form of Helicobacter pylori, as a complement to the results obtained from various animal models. Egg passage was performed, as it is a simple, rapid, and well-characterized old method by which to culture and evaluate culturability of bacteria compared to experiments in animal models. Egg passage has been used in such experiments since 1938 for isolation and growth of, for example, Rickettsiae sp. and Chlamydia sp., Materials and Methods: The rod-shaped form of H. pylori was produced by plate cultures for 4 and 7 days. The coccoid form of H. pylori was produced by culture on agar plates for 10 days, followed by storage in water. These preparations then were inoculated into the yolk sac of differently aged fertilized eggs., Results: Positive culture was obtained from 14 of 17 eggs (82%) inoculated with rod-shaped H. pylori compared to 0 of 22 eggs (0%) inoculated with the coccoid form., Conclusion: Culturability of H. pylori is reduced when it converts into the coccoid form produced by starvation and age followed by storage in water for several weeks at room temperature. Egg passage did not raise the culturability of the coccoid form of H. pylori. Our study demonstrates some clear differences between fresh rods and stored cocci forms of H. pylori in terms of culturability when passed through eggs.