Helicobacter pylori Infection: Detection and Novel Treatment

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (31 July 2025) | Viewed by 10911

Special Issue Editor


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Guest Editor
Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
Interests: Helicobacter pylori; microbial molecular biology; antibiotic resistance

Special Issue Information

Dear Colleagues,

Helicobacter pylori has long been recognized as a formidable player in the realm of gastrointestinal health, significantly impacting the global burden of digestive and various extragastric diseases. The complexity of H. pylori infection necessitates continuous exploration and innovation in diagnostic techniques and treatment modalities.

In this collection of articles, we bring together a diverse range of contributions that highlight groundbreaking research aiming to not only enhance our ability to accurately detect the bacterium in different clinical contexts, but also pioneer innovative therapeutic approaches designed to address antibiotic resistance and optimize patient outcomes. From long-established diagnostic methods such as serology and endoscopy to cutting-edge technologies such as next-generation sequencing, this Special Issue offers a novel perspective on their evolving role in precision medicine and personalized treatment plans. Furthermore, alternative therapeutic avenues, including the use of bacteriophages, probiotics and plant-derived compounds, vaccines and nanotechnology, emerge as promising areas of research explored for their potential in preventing and treating H. pylori-associated diseases.

We anticipate that this compilation will serve as a valuable resource for researchers, clinicians and policymakers, fostering a deeper understanding of the latest advancements, challenges and breakthroughs in the dynamic landscape of Helicobacter pylori research, ultimately paving the way for improved patient care and public health outcomes.

Dr. Evangelos Kazakos
Guest Editor

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Keywords

  • Helicobacter pylori
  • gastrointestinal health
  • antibiotic resistance
  • infection

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Published Papers (7 papers)

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Research

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13 pages, 604 KB  
Article
Helicobacter pylori Diagnostic Testing Accuracy in a High-Prevalence Native American Population of Northern Arizona
by Heidi E. Brown, Laura Pauli, Rishi Dholakia, Joseph Gunderson, Julia Jernberg, Priscilla R. Sanderson, Robin B. Harris and Fernando P. Monroy
Microorganisms 2025, 13(8), 1920; https://doi.org/10.3390/microorganisms13081920 - 18 Aug 2025
Viewed by 499
Abstract
Helicobacter pylori (H. pylori) is a common gastric pathogen and a leading cause of non-cardia gastric cancers. Known determinants can affect the diagnostic accuracy of invasive clinical methods for H. pylori diagnosis. The objective of this study was to determine the diagnostic [...] Read more.
Helicobacter pylori (H. pylori) is a common gastric pathogen and a leading cause of non-cardia gastric cancers. Known determinants can affect the diagnostic accuracy of invasive clinical methods for H. pylori diagnosis. The objective of this study was to determine the diagnostic accuracy of the CLOtest, a rapid urease test, and the histopathologic examination compared with polymerase chain reaction (PCR) in esophagogastroduodenoscopy patients from a population with high prevalence and other risk factors that may influence diagnostic accuracy. From 2018 to 2022, patients were recruited from a medical care center serving the southwestern Navajo Nation. Summary statistics were calculated using PCR as the comparator to the CLOtest and histopathologic examination. Among the 466 study participants, 27.1% (95% CI 22.9, 31.7%) tested positive for H. pylori using PCR to detect pathogen DNA. Sensitivity was lowest for the CLOtest (57.0%; 95% CI 45.8, 67.6) and highest for the combination the CLOtest and histopathology (72.2%; 95% CI 62.8, 80.4). Patient history of infection or possible GI bleeding influenced sensitivity by over 5%. In high H. pylori prevalence areas, emphasis should be placed on ensuring adequate treatment of suspected positive infections as false-positive results were rare. Including a more sensitive test might reduce the number of individuals falsely classified as H. pylori negative. Full article
(This article belongs to the Special Issue Helicobacter pylori Infection: Detection and Novel Treatment)
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21 pages, 3401 KB  
Article
Allelic Variation of Helicobacter pylori vacA Gene and Its Association with Gastric Pathologies in Clinical Samples Collected in Jordan
by Mamoon M. Al-Hyassat, Hala I. Al-Daghistani, Lubna F. Abu-Niaaj, Sima Zein and Talal Al-Qaisi
Microorganisms 2025, 13(8), 1841; https://doi.org/10.3390/microorganisms13081841 - 7 Aug 2025
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Abstract
Helicobacter pylori is a well-established causative agent of gastritis, peptic ulcers, gastric adenocarcinoma, and primary gastric lymphoma. It colonizes the human stomach and expresses numerous virulent factors that influence disease progression. Among these factors is the cytotoxin vacA gene, which encodes the vacuolating [...] Read more.
Helicobacter pylori is a well-established causative agent of gastritis, peptic ulcers, gastric adenocarcinoma, and primary gastric lymphoma. It colonizes the human stomach and expresses numerous virulent factors that influence disease progression. Among these factors is the cytotoxin vacA gene, which encodes the vacuolating capacity of the cytotoxin and plays a key role in the bacterium’s pathogenic potential. This study investigated the allelic diversity of the vacA among H. pylori strains infecting patients in Jordan with various gastric conditions and examined potential associations between vacA s-and m- genotypes, histopathological and endoscopic findings, and the development of gastric diseases. Gastric biopsies were collected from 106 patients at two hospitals in Jordan who underwent endoscopic examination. The collected biopsies for each patient were subjected to histopathological assessment, urease detection using the Rapid Urease Test (RUT), a diagnostic test for H. pylori, and molecular detection of the vacA gene and its s and m alleles. The histopathology reports indicated that 83 of 106 patients exhibited gastric disorders, of which 81 samples showed features associated with H. pylori infection. The RUT was positive in 76 of 106 with an accuracy of 93.8%. Real-time polymerase chain reaction (RT-PCR) targeting the 16S rRNA gene confirmed the presence of H. pylori in 79 of 81 histologically diagnosed cases as infected (97.5%), while the vacA gene was detected only in 75 samples (~95%). To explore genetic diversity, PCR-amplified fragments underwent sequence analysis of the vacA gene. The m-allele was detected in 58 samples (73%), the s-allele was detected in 45 (57%), while both alleles were not detected in 13% of samples. The predominant genotype combination among Jordanians was vacA s2/m2 (50%), significantly linked to mild chronic gastritis, followed by s1/m2 (35%) and s1/m1 (11.8%) which are linked to severe gastric conditions including malignancies. Age-and gender-related differences in vacA genotype were observed with less virulent s2m2 and s1m2 genotypes predominating in younger adults specially males, while the more virulent m1 genotypes were found exclusively in females and middle-aged patients. Genomic sequencing revealed extensive diversity within H. pylori, likely reflecting its long-standing co-evolution with human hosts in Jordan. This genetic variability plays a key role in modulating virulence and influencing clinical outcomes. Comprehensive characterization of vacA genotypic variations through whole-genome sequencing is essential to enhance diagnostic precision, strengthen epidemiological surveillance, and inform targeted therapeutic strategies. While this study highlights the significance of the vacA m and s alleles, future research is recommended in order to investigate the other vacA allelic variations, such as the i, d, and c alleles, to achieve a more comprehensive understanding of H. pylori pathogenicity and associated disease severity across different strains. These investigations will be crucial for improving diagnostic accuracy and guiding the development of targeted therapeutic strategies. Full article
(This article belongs to the Special Issue Helicobacter pylori Infection: Detection and Novel Treatment)
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12 pages, 2523 KB  
Article
Evaluation of the Rapid Urease Test (RUT) Device for Rapid Diagnosis of Helicobacter pylori in Middle-Aged and Elderly Taiwanese Patients
by Kuan-Yi Yu, Yu-Chuan Chuang, Tien-Yu Huang, Hua-Kang Chou, Ying-Tsang Lu, Juin-Hong Cherng and Cheng-Che Liu
Microorganisms 2025, 13(4), 767; https://doi.org/10.3390/microorganisms13040767 - 28 Mar 2025
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Abstract
The rapid urease test (RUT) is a reliable method for diagnosing Helicobacter pylori infections in endoscopy suites; however, there is a need for tests with enhanced sensitivity and faster results. This study aimed to evaluate the diagnostic performance of the new dry detection [...] Read more.
The rapid urease test (RUT) is a reliable method for diagnosing Helicobacter pylori infections in endoscopy suites; however, there is a need for tests with enhanced sensitivity and faster results. This study aimed to evaluate the diagnostic performance of the new dry detection device test compared to the gel detection device and Pronto Dry RUT in detecting Helicobacter pylori infection among middle-aged and elderly Taiwanese individuals. A total of 100 participants with suspected Helicobacter pylori infection undergoing upper gastroscopy were prospectively enrolled. The dry detection device demonstrated a 99% concordance rate with the Pronto Dry RUT, with seven participants testing positive for Helicobacter pylori using both tests. In contrast, the gel detection device detected only six positive cases, highlighting the superior diagnostic sensitivity of the dry detection device. Additionally, the dry detection device produced significantly faster results than the gel detection device. These findings suggest that the dry detection device is a suitable and efficient RUT for diagnosing Helicobacter pylori in middle-aged and elderly patients. Further studies are warranted to explore its application in broader populations and clinical settings. Full article
(This article belongs to the Special Issue Helicobacter pylori Infection: Detection and Novel Treatment)
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13 pages, 1801 KB  
Article
Concordance of Helicobacter pylori Detection Methods in Symptomatic Children and Adolescents
by Camila Cabrera, Yanira Campusano, Joaquín Torres, Dinka Ivulic, Valeria Galvez, Diego Tapia, Vicente Rodríguez, Anne Lagomarcino, Alejandra Gallardo, Francisco Alliende, Marcela Toledo, Gabriela Román, Francisca Jaime, Mónica González, Pamela Marchant, Marianela Rojas, Juan Ignacio Juanet, Mónica Villanueva, Juan Cristobal Ossa, Felipe Del Canto, Tomeu Viver, Miguel O’Ryan and Yalda Luceroadd Show full author list remove Hide full author list
Microorganisms 2025, 13(3), 583; https://doi.org/10.3390/microorganisms13030583 - 4 Mar 2025
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Abstract
Background: Helicobacter pylori is the most prevalent chronic bacterial infection globally, acquired mostly during childhood. It is associated with chronic gastritis, peptic ulcer disease, and gastric cancer. Due to challenges in culturing H. pylori, diagnostic reference standards often rely on combining ≥2 [...] Read more.
Background: Helicobacter pylori is the most prevalent chronic bacterial infection globally, acquired mostly during childhood. It is associated with chronic gastritis, peptic ulcer disease, and gastric cancer. Due to challenges in culturing H. pylori, diagnostic reference standards often rely on combining ≥2 non-culture, biopsy-based methods. Histology with Giemsa staining is widely used in clinical settings due to its low cost and reliable performance. Methods: This study evaluated the concordance between histology with Giemsa staining as the reference standard and other diagnostic methods, including the rapid urease test (RUT), ureA RT-PCR, 16S sequencing, and anti-H. pylori serum IgG. Positive percent of agreement (PPA), negative percent of agreement (NPA) and concordance kappa index were calculated. Results: A total of 120 patients (41 positive and 79 negative by Giemsa staining) were analyzed. Among the methods tested, RT-PCR for ureA showed the best performance (PPA = 94.7%, NPA = 98.6%, kappa = 0.939), while RUT underperformed compared with expectations (PPA = 65.9%, NPA = 97.5%, kappa = 0.681). Serology had the lowest performance (PPA = 53.7%, NPA = 96.1%, kappa = 0.548). Conclusions: The combination of histology with Giemsa staining and ureA RT-PCR achieved the highest detection rate and strongest agreement. Full article
(This article belongs to the Special Issue Helicobacter pylori Infection: Detection and Novel Treatment)
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13 pages, 337 KB  
Article
Antibiotic Susceptibility-Guided Concomitant Therapy Regimen with Vonoprazan, High-Dose Amoxicillin, Clarithromycin, and Metronidazole for Helicobacter pylori Eradication as Fourth-Line Regimen: An Interventional Study
by Soichiro Sue, Takeshi Sato, Mao Matsubayashi, Hiroaki Kaneko, Kuniyasu Irie and Shin Maeda
Microorganisms 2024, 12(10), 2104; https://doi.org/10.3390/microorganisms12102104 - 21 Oct 2024
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Abstract
This is the first registered intervention study for vonoprazan, high-dose amoxicillin, clarithromycin, and metronidazole 14-day concomitant therapy based on a susceptibility test of Helicobacter pylori. We conducted this study as a fourth-line rescue regimen in Japan. Methods: Twenty patients who underwent three [...] Read more.
This is the first registered intervention study for vonoprazan, high-dose amoxicillin, clarithromycin, and metronidazole 14-day concomitant therapy based on a susceptibility test of Helicobacter pylori. We conducted this study as a fourth-line rescue regimen in Japan. Methods: Twenty patients who underwent three rounds of eradication therapies (first- or second-line 7-day triple therapy consisting of amoxicillin and clarithromycin, or metronidazole- and sitafloxacin-based third-line therapy) and had failed eradication based on a urea breath test or fecal antigen test were recruited. All patients underwent endoscopic examination and culture tests before starting eradication therapy. The intervention was concomitant therapy consisting of vonoprazan 20 mg bid, amoxicillin 500 mg qid, clarithromycin 400 mg bid, and metronidazole 250 mg bid for 14 days, which were modified based on the susceptibility test, and the resistant drugs were removed from the regimen. Patients with negative culture results were treated with quadruple therapy. The primary outcome was the eradication rate (UMIN000025765, jRCTs 031180208). Results: The eradication rate of susceptibility-testing-based fourth-line eradication therapy was 63.2% (95%CI: 38.4–83.7%) in intent-to-treat analysis and 70.6% (95%CI: 44.0–89.7%) in per-protocol analysis. Thirteen patients received quadruple therapy, with eradication rates of 61.5% and 75.0%, respectively. No serious adverse events were reported. Conclusions: This vonoprazan-based concomitant therapy modified by the susceptibility test is a potential option as fourth-line eradication after first-line clarithromycin-based 7-day triple, second-line metronidazole-based 7-day triple, and third-line sitafloxacin-based 7-day triple therapy failure. Full article
(This article belongs to the Special Issue Helicobacter pylori Infection: Detection and Novel Treatment)
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8 pages, 208 KB  
Communication
Factors Influencing the Degree of Gastric Atrophy in Helicobacter pylori Eradication Patients with Drinking Habits
by Kayoko Ozeki, Kazuhiro Hada and Yoshifumi Wakiya
Microorganisms 2024, 12(7), 1398; https://doi.org/10.3390/microorganisms12071398 - 10 Jul 2024
Cited by 2 | Viewed by 1831
Abstract
Chronic gastritis caused by Helicobacter pylori (H. pylori) infection can lead to gastric atrophy. This study aimed to identify the factors associated with gastric atrophy in H. pylori eradication patients with drinking habits. Of the 250 patients who visited Hamamatsu University [...] Read more.
Chronic gastritis caused by Helicobacter pylori (H. pylori) infection can lead to gastric atrophy. This study aimed to identify the factors associated with gastric atrophy in H. pylori eradication patients with drinking habits. Of the 250 patients who visited Hamamatsu University Hospital for H. pylori eradication and underwent eradication treatment between April 2017 and December 2020, 127 patients with drinking habits were included in this study. The degree of gastric atrophy of the patients was classified based on endoscopy. The relationship between patient attributes (sex, age, alcohol consumption, frequency of drinking, smoking status, and medication use) and a highly atrophic stomach was statistically analyzed. The results showed that gastric atrophy was significantly higher in males and in those aged 60 years or older and that gastric atrophy tended to be higher in those who drank 20 g or more per day and 5 days or more a week. There was also a trend toward higher atrophy in sake drinkers and lower atrophy in wine drinkers. This study provides useful knowledge for patient management and guidance after H. pylori eradication treatment and indicates the importance of comprehensive measures, including alcohol consumption control and lifestyle modification, especially for men and older people. Full article
(This article belongs to the Special Issue Helicobacter pylori Infection: Detection and Novel Treatment)

Review

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24 pages, 1005 KB  
Review
The Potential Role of Helicobacter pylori-Related Mast Cell Activation in the Progression from Gastroesophageal Reflux to Barrett’s Esophagus and Esophageal Adenocarcinoma
by Evangelos I. Kazakos, Efthymia Petinaki, Christos Liatsos, Ioannis S. Papanikolaou, Kyriaki Anastasiadou and Jannis Kountouras
Microorganisms 2025, 13(8), 1883; https://doi.org/10.3390/microorganisms13081883 - 12 Aug 2025
Viewed by 710
Abstract
Helicobacter pylori (Hp), a widespread gastric pathogen, has long been studied for its role in upper gastrointestinal disorders. While its involvement in gastritis, peptic ulcer disease, and gastric cancer is well established, its impact on esophageal diseases remains an area of [...] Read more.
Helicobacter pylori (Hp), a widespread gastric pathogen, has long been studied for its role in upper gastrointestinal disorders. While its involvement in gastritis, peptic ulcer disease, and gastric cancer is well established, its impact on esophageal diseases remains an area of ongoing investigation. Nevertheless, some data indicate that Hp may be involved in the pathogenesis of gastroesophageal reflux disease–Barrett’s esophagus–esophageal adenocarcinoma sequence. Similarly, the Hp-related mast cell activation—an essential immunological event—may also play a crucial role in the progression from gastroesophageal reflux disease to Barrett’s esophagus and esophageal adenocarcinoma. The underlying mechanisms include immune modulation, cytokine cascades, and microbial interactions that collectively shape the esophageal microenvironment. This review provides an in-depth analysis of these pathways, highlighting the potential role of Hp-induced, mast cell-driven inflammation in esophageal disease progression and discussing emerging therapeutic strategies. Full article
(This article belongs to the Special Issue Helicobacter pylori Infection: Detection and Novel Treatment)
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