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Real-Time PCR Helicobacter pylori Test in Comparison With Culture and Histology for Helicobacter pylori Detection and Identification of Resistance to Clarithromycin: A Single-Center Real-Life Study
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-04-07 DOI: 10.1111/hel.70031
Kateryna Priadko, Sophie-Anne Gibaud, Amaury Druet, Louise Galmiche, Francis Megraud, Stéphane Corvec, Tamara Matysiak-Budnik

Background

In our center, RT-PCR was integrated as a routine method to diagnose Helicobacter pylori due to its higher availability after COVID-19 pandemics. The objective of this study was to assess the feasibility and performance of systematically performed RT-PCR for H. pylori detection and clarithromycin (CLA) resistance in a real-life clinical practice.

Materials and Methods

One hundred consecutive patients underwent an upper digestive endoscopy during which at least four biopsies (two from the antrum and two from the corpus) were obtained for RT-PCR and culture with antibiogram and four additional biopsies for histology. The results of H. pylori detection were compared among RT-PCR, histology, and bacterial culture, and the results of CLA susceptibility were compared between culture-based antibiogram and RT-PCR.

Results

Out of 100 patients, 64 were positive for H. pylori by RT-PCR, 66 by histology, and 53 by culture, with no statistically significant difference among the three methods (p > 0.05). CLA resistance was found in 8 out of 45 patients (17.7%) by culture and in 12 out of 64 patients (18.7%) by PCR. In 8 H. pylori-positive patients by culture, the antibiogram could not be realized due to lack of viability of the strains. In one patient, after a double checking, discrepant results were observed, requiring a complementary molecular analysis by the French National Reference Center for Helicobacters, which confirmed the existence of a double population of H. pylori strains within biopsies, with and without CLA resistance.

Conclusions

Our study demonstrates that in real-life clinical practice, RT-PCR is feasible and comparable in the ability to detect H. pylori and its resistance to CLA to bacterial culture with antibiogram and histology. Given its rapidity and limited dependence on the operator's interpretation, it appears preferable to the other methods.

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引用次数: 0
First-Line Therapy for Helicobacter pylori in Slovenia: Data From 2013 to 2023 of the European Registry on H. pylori Management
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-04-03 DOI: 10.1111/hel.70029
Bojan Tepes, Nataša Brglez Jurečič, Maja Denkovski, Miroslav Vujasinovič, Zdenko Kikec, Jurij Bednarik, Katja Tepes, Anna Cano-Català, Pablo Parra, Leticia Moreira, Olga P. Nyssen, Francis Mégraud, Colm O'Morain, Javier P. Gisbert

Background

Treatment is indicated for all Helicobacter pylori infections. However, the best approach for H. pylori management remains unclear.

Methods

H. pylori eradication data from Hp-EuReg on treatment-naive patients in Slovenia from 2013 to 2023 were included. The regimens prescribed, the number of eradication attempts, effectiveness, adherence, and safety were analyzed. The effectiveness was assessed by modified intention to treat (mITT).

Results

Eight Slovenian medical institutions contributed data for 4016 treatment-naive patients to Hp-EuReg. Of these, 18% did not undergo confirmatory post-treatment; most who did received a urea breath test. Between 2013 and 2018, 7-day triple therapy with amoxicillin and clarithromycin was most frequently used in first-line treatment, with an 88% eradication rate. From 2019 to 2023, a 14-day high-dose PPI (esomeprazole 40 mg b.i.d.) triple therapy with amoxicillin and clarithromycin was used, showing a significantly higher effectiveness at 94% (p < 0.05). Quadruple bismuth-based therapy (esomeprazole 40 mg b.i.d., plus amoxicillin 500 mg, metronidazole 400 mg, and bismuth 120 mg, all q.i.d.) provided a 96.9% eradication rate, though this was not significantly better than the 14-day triple regimen. The H. pylori resistance rate to clarithromycin was 16% from 2013 to 2018, dropping to 13.5% from 2019 to 2023. Side effects were reported by 9.6% of patients, and treatment compliance was > 99%.

Conclusions

The study suggests that systematic data collection from routine clinical practice in Hp-EuReg can guide first-line H. pylori treatment. Established 90% treatment effectiveness threshold may serve as a surrogate marker for monitoring H. pylori resistance rates to antibiotics. In countries with a H. pylori resistance rate < 15%, such as Slovenia, the 14-day high-dose PPI amoxicillin-clarithromycin regimen is an optimal first-line empirical treatment.

Trial Registration: NCT02328131

背景 所有幽门螺旋杆菌感染都需要治疗。然而,治疗幽门螺杆菌的最佳方法仍不明确。 方法 本文纳入了 Hp-EuReg 提供的 2013 年至 2023 年斯洛文尼亚接受过治疗的患者的幽门螺杆菌根除数据。对处方方案、根除尝试次数、有效性、依从性和安全性进行了分析。疗效通过改良意向治疗(mITT)进行评估。 结果 8 家斯洛文尼亚医疗机构向 Hp-EuReg 提供了 4016 名未经治疗患者的数据。其中,18%的患者未接受治疗后确诊;大部分接受治疗的患者接受了尿素呼气试验。2013年至2018年期间,阿莫西林和克拉霉素的7天三联疗法最常用于一线治疗,根除率为88%。从2019年到2023年,使用了14天大剂量PPI(埃索美拉唑40毫克,每天两次)与阿莫西林和克拉霉素的三联疗法,显示出显著较高的有效率,达到94%(p <0.05)。以铋剂为基础的四联疗法(埃索美拉唑 40 毫克,每天两次,外加阿莫西林 500 毫克、甲硝唑 400 毫克和铋剂 120 毫克,每天三次)的根除率为 96.9%,但与 14 天的三联疗法相比,效果并不明显。2013年至2018年,克拉霉素的幽门螺杆菌耐药率为16%,2019年至2023年降至13.5%。9.6%的患者报告了副作用,治疗依从性为> 99%。 结论 该研究表明,从 Hp-EuReg 的常规临床实践中系统地收集数据可以指导幽门螺杆菌的一线治疗。既定的 90% 治疗有效阈值可作为监测幽门螺杆菌对抗生素耐药率的替代指标。在幽门螺杆菌耐药率为15%的国家,如斯洛文尼亚,14天大剂量PPI阿莫西林-卡里霉素方案是最佳的一线经验性治疗方案。 试验注册:NCT02328131
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引用次数: 0
Helicobacter pylori Eradication Is Associated With a Reduced Risk of Metachronous Gastric Neoplasia by Restoring Immune Function in the Gastric Mucosa
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-04-01 DOI: 10.1111/hel.70030
Min-Jae Kim, Yeonjin Je, Jaeyoung Chun, Young Hoon Youn, Hyojin Park, Ji Hae Nahm, Jie-Hyun Kim

Background

Helicobacter pylori infection is a significant contributing factor of gastric cancer. Metachronous neoplasms also pose a risk. The mechanism underlying the impact of H. pylori eradication on preventing metachronous gastric cancer is unclear. This study aimed to investigate immunity changes in gastric mucosa after H. pylori eradication and to identify mechanisms preventing metachronous recurrence.

Materials and Methods

Patients diagnosed with gastric neoplasm and H. pylori infection, who underwent endoscopic resection, were included. Thirty-six cases of metachronous neoplasms occurring after eradication (metachronous group) were compared to 36 controls matched for age, sex, atrophy, and metaplasia (control group). Histological features and immunohistochemical staining for T-cell (CD3, CD4, and CD8) and immune exhaustion (forkhead/winged helix transcription factor and programmed cell death-ligand 1) markers in the non-tumor-bearing mucosa were evaluated.

Results

In histologic features, glandular atrophy and intestinal metaplasia in the gastric mucosa significantly improved following H. pylori eradication in the control group (p < 0.001, 0.008), whereas they did not improve in the metachronous group (p = 0.449, 0.609). CD8 and CD8/CD3 ratios increased in the control group (p < 0.001, 0.04), but did not show differences in the metachronous group (p = 0.057, 0.245). The CD4/CD3 ratio and programmed cell death-ligand 1/CD4 expression significantly decreased after H. pylori eradication in the control group (p = 0.003, 0.042), but not in the metachronous group (p = 0.54, 0.55).

Conclusions

This observational study suggests that H. pylori eradication may prevent the recurrence of gastric neoplasia by improving histological inflammation and overcoming immune exhaustion.

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引用次数: 0
Management of Helicobacter pylori Infection in Spain Beyond the Data Collected in the European Registry on H. pylori Management (Hp-EuReg): Results of a Nationwide Survey
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-04-01 DOI: 10.1111/hel.70028
Javier Tejedor-Tejada, Samuel J. Martínez-Domínguez, Luis Hernández, Anna Cano-Català, Pablo Parra, Leticia Moreira, Olga P. Nyssen, Javier P. Gisbert, the Hp-EuReg Investigators

Background

The management of Helicobacter pylori (H. pylori) infection encompasses different diagnostic and therapeutic procedures.

Materials and Methods

A survey was developed to investigate further factors of the clinical practice concerning the management of H. pylori infection that are currently not collected within the European Registry on H. pylori Management (Hp-EuReg). The survey was distributed among Spanish Hp-EuReg investigators, members of the Spanish Gastroenterology Association, and through social media.

Results

Overall, 128 investigators from all Spanish regions participated (79% from centers enrolling patients in the Hp-EuReg). Most participants (66%) reported having at least five diagnostic methods available. Culture was usually performed following the second-line failure (64%). Contrary to the recommendations, 17% of physicians did not investigate H. pylori infection in patients admitted for peptic ulcer bleeding, and 35% did not treat the infection right away. Furthermore, most investigators (95%) did not test for the infection in cohabitants, and 32% in gastric cancer relatives. The test-and-treat strategy was used in 84% of patients under 55 years without alarm symptoms, and in 15% of patients over 55 years. The majority (74%) did not confirm the penicillin allergy, only 26% were aware of the local clarithromycin resistance rate, and 37% periodically evaluated the efficacy of eradication treatments. Finally, most Spanish investigators (83%) followed the V Spanish Consensus, while up to 35% followed the Maastricht VI recommendation guidelines.

Conclusions

The management of H. pylori infection in Spain is suboptimal, even among Hp-EuReg investigators. We must optimize H. pylori management by implementing educational measures adapted to each setting.

Trial Registration

ClinicalTrials.gov: NCT02328131

背景幽门螺旋杆菌(H. pylori)感染的治疗包括不同的诊断和治疗程序。 材料和方法 为了进一步调查欧洲幽门螺杆菌管理登记处(Hp-EuReg)目前尚未收集的有关幽门螺杆菌感染管理的临床实践因素,我们开展了一项调查。调查问卷在西班牙 Hp-EuReg 调查员、西班牙消化病协会会员中进行了发放,并通过社交媒体进行了传播。 结果 共有来自西班牙所有地区的 128 名调查员参与了调查(79% 来自 Hp-EuReg 患者登记中心)。大多数参与者(66%)称至少有五种诊断方法可用。培养通常在二线诊断失败后进行(64%)。与建议相反,17% 的医生没有对因消化性溃疡出血入院的患者进行幽门螺杆菌感染检查,35% 的医生没有立即治疗感染。此外,大多数调查人员(95%)没有检测同居者是否感染幽门螺杆菌,32%没有检测胃癌亲属是否感染幽门螺杆菌。在 55 岁以下无报警症状的患者中,84% 采用了先检测后治疗的策略,在 55 岁以上的患者中,15% 采用了先检测后治疗的策略。大多数人(74%)没有确认青霉素过敏,只有 26% 的人知道当地克拉霉素的耐药率,37% 的人定期评估根除治疗的疗效。最后,大多数西班牙调查人员(83%)遵循第五次西班牙共识,而遵循第六次马斯特里赫特建议指南的调查人员则高达 35%。 结论 在西班牙,幽门螺杆菌感染的治疗效果并不理想,即使在 Hp-EuReg 研究人员中也是如此。我们必须根据不同的环境采取相应的教育措施,优化幽门螺杆菌的管理。 试验注册 ClinicalTrials.gov:NCT02328131
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引用次数: 0
Artificial Intelligence in Endoscopy for Predicting Helicobacter pylori Infection: A Systematic Review and Meta-Analysis
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-03-21 DOI: 10.1111/hel.70026
Yiwen Jiang, Hengxu Yan, Jiatong Cui, Kaiqiang Yang, Yue An

Purpose

This meta-analysis aimed to assess the diagnostic performance of artificial intelligence (AI) based on endoscopy for detecting Helicobacter pylori (H. pylori) infection.

Methods

A comprehensive literature search was conducted across PubMed, Embase, and Web of Science to identify relevant studies published up to January 10, 2025. The selected studies focused on the diagnostic accuracy of AI in detecting H. pylori. A bivariate random-effects model was employed to calculate pooled sensitivity and specificity, both presented with 95% confidence intervals (CIs). Study heterogeneity was assessed using the I2 statistic.

Results

Of 604 studies identified, 16 studies (25,002 images or patients) were included. For the internal validation set, the pooled sensitivity, specificity, and area under the curve (AUC) for detecting H. pylori were 0.91 (95% CI: 0.84–0.95), 0.91 (95% CI: 0.86–0.94), and 0.96 (95% CI: 0.94–0.97), respectively. For the external validation set, the pooled sensitivity, specificity, and AUC were 0.91 (95% CI: 0.86–0.95), 0.94 (95% CI: 0.90–0.97), and 0.98 (95% CI: 0.96–0.99). For junior clinicians, the pooled sensitivity, specificity, and AUC were 0.76 (95% CI: 0.66–0.83), 0.75 (95% CI: 0.70–0.80), and 0.81 (95% CI: 0.77–0.84). For senior clinicians, the pooled sensitivity, specificity, and AUC were 0.81 (95% CI: 0.74–0.86), 0.89 (95% CI: 0.86–0.91), and 0.92 (95% CI: 0.90–0.94).

Conclusions

Endoscopy-based AI demonstrates higher diagnostic performance compared to both junior and senior endoscopists. However, the high heterogeneity among studies limits the strength of these findings, and further research with external validation datasets is necessary to confirm the results.

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引用次数: 0
Letter to the Editor: “Efficacy of Lactobacillus spp. Supplementation in Helicobacter pylori Eradication: A Systematic Meta-Analysis of Randomized Controlled Trials With Trial Sequential Analysis”
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-03-20 DOI: 10.1111/hel.70027
Ben-Gang Zhou, Yao-Yao Li, Yan-Bing Ding
{"title":"Letter to the Editor: “Efficacy of Lactobacillus spp. Supplementation in Helicobacter pylori Eradication: A Systematic Meta-Analysis of Randomized Controlled Trials With Trial Sequential Analysis”","authors":"Ben-Gang Zhou,&nbsp;Yao-Yao Li,&nbsp;Yan-Bing Ding","doi":"10.1111/hel.70027","DOIUrl":"10.1111/hel.70027","url":null,"abstract":"","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Innate Immunity in Helicobacter pylori Infection and Gastric Oncogenesis
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-03-17 DOI: 10.1111/hel.70015
Yuheng Zhang, Zhiyu Yan, Yuhao Jiao, Yunlu Feng, Shengyu Zhang, Aiming Yang

Helicobacter pylori is an extremely common cause of gastritis that can lead to gastric adenocarcinoma over time. Approximately half of the world's population is infected with H. pylori, making gastric cancer the fourth leading cause of cancer-related deaths worldwide. Innate immunity significantly contributes to systemic and local immune responses, maintains homeostasis, and serves as the vital link to adaptive immunity, and in doing so, mediates H. pylori infection outcomes and consequent cancer risk and development. The gastric innate immune system, composed of gastric epithelial and myeloid cells, is uniquely challenged by its need to interact simultaneously and precisely with commensal microbiota, exogenous pathogens, ingested substances, and endogenous exfoliated cells. Additionally, innate immunity can be detrimental by promoting chronic infection and fibrosis, creating an environment conducive to tumor development. This review summarizes and discusses the complex role of innate immunity in H. pylori infection and subsequent gastric oncogenesis, and in doing so, provides insights into how these pathways can be exploited to improve prevention and treatment.

幽门螺杆菌是导致胃炎的一种极为常见的病因,随着时间的推移可导致胃腺癌。全球约有一半人口感染幽门螺杆菌,胃癌已成为全球癌症相关死亡的第四大主要原因。先天性免疫对全身和局部免疫反应、维持体内平衡以及作为适应性免疫的重要环节做出了重大贡献,并因此介导了幽门螺杆菌感染的结果以及随之而来的癌症风险和发展。胃先天性免疫系统由胃上皮细胞和髓样细胞组成,需要同时与共生微生物群、外源性病原体、摄入物质和内源性脱落细胞进行精确互动,因此面临着独特的挑战。此外,先天性免疫还可能会促进慢性感染和纤维化,为肿瘤的发展创造有利环境,从而造成危害。本综述总结并讨论了先天性免疫在幽门螺杆菌感染和随后的胃癌发生过程中的复杂作用,并由此深入探讨了如何利用这些途径改善预防和治疗。
{"title":"Innate Immunity in Helicobacter pylori Infection and Gastric Oncogenesis","authors":"Yuheng Zhang,&nbsp;Zhiyu Yan,&nbsp;Yuhao Jiao,&nbsp;Yunlu Feng,&nbsp;Shengyu Zhang,&nbsp;Aiming Yang","doi":"10.1111/hel.70015","DOIUrl":"https://doi.org/10.1111/hel.70015","url":null,"abstract":"<p><i>Helicobacter pylori</i> is an extremely common cause of gastritis that can lead to gastric adenocarcinoma over time. Approximately half of the world's population is infected with <i>H. pylori</i>, making gastric cancer the fourth leading cause of cancer-related deaths worldwide. Innate immunity significantly contributes to systemic and local immune responses, maintains homeostasis, and serves as the vital link to adaptive immunity, and in doing so, mediates <i>H. pylori</i> infection outcomes and consequent cancer risk and development. The gastric innate immune system, composed of gastric epithelial and myeloid cells, is uniquely challenged by its need to interact simultaneously and precisely with commensal microbiota, exogenous pathogens, ingested substances, and endogenous exfoliated cells. Additionally, innate immunity can be detrimental by promoting chronic infection and fibrosis, creating an environment conducive to tumor development. This review summarizes and discusses the complex role of innate immunity in <i>H. pylori</i> infection and subsequent gastric oncogenesis, and in doing so, provides insights into how these pathways can be exploited to improve prevention and treatment.</p>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hel.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Flagellar Assembly Factor FliW2 De-Represses Helicobacter pylori FlaA-Mediated Motility by Allosteric Obstruction of Global Regulator CsrA
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-03-13 DOI: 10.1111/hel.70019
Marcia Shu-Wei Su, Benjamin Dickins, Fang Yie Kiang, Wei-Jiun Tsai, Yueh-Lin Chen, Jenn-Wei Chen, Shuying Wang, Pei-Jane Tsai, Jiunn-Jong Wu

Background

Helicobacter pylori colonizes the human stomach as a dominant member of the gastric microbiota and constitutively expresses flagellar motility for survival. Carbon storage regulator A (CsrA) is a posttranscriptional global regulator and a critical determinant of H. pylori's motility and pathogenicity. The regulation of H. pylori CsrA is still uncertain although in other species CsrA is reported to be antagonized by small RNAs and proteins. In this study, we attempted to unveil how CsrA is regulated and hypothesized that H. pylori CsrA activity is antagonized by a flagellar assembly factor, FliW2, via protein allosteric obstruction.

Materials and Methods

Multiple sequence comparisons indicated that, along its length and in contrast to fliW1, the fliW2 of H. pylori J99 is conserved. We then generated an isogenic ΔfliW2 strain whose function was characterized using phenotypic and biochemical approaches. We also applied a machine learning approach (AlphaFold2) to predict FliW2-CsrA binding domains and investigated the FliW2-CsrA interaction using pull-down assays and in vivo bacterial two-hybrid systems.

Results

We observed the reduced expression of major flagellin FlaA and impaired flagellar filaments that attenuated the motility of the ΔfliW2 strain. Furthermore, a direct interaction between FliW2 and CsrA was demonstrated, and a novel region of the C-terminal extension of CsrA was suggested to be crucial for CsrA interacting with FliW2. Based on our AlphaFold2 prediction, this C-terminal region of FliW2-CsrA interaction does not overlap with CsrA's N-terminal RNA binding domain, implying that FliW2 allosterically antagonizes CsrA activity and restricts CsrA's binding to flaA mRNAs.

Conclusions

Our data points to novel regulatory roles that the H. pylori flagellar assembly factor FliW2 has in obstructing CsrA activity, and thus FliW2 may indirectly antagonize CsrA's regulation of flaA mRNA processing and translation. Our findings reveal a new regulatory mechanism of flagellar motility in H. pylori.

{"title":"Flagellar Assembly Factor FliW2 De-Represses Helicobacter pylori FlaA-Mediated Motility by Allosteric Obstruction of Global Regulator CsrA","authors":"Marcia Shu-Wei Su,&nbsp;Benjamin Dickins,&nbsp;Fang Yie Kiang,&nbsp;Wei-Jiun Tsai,&nbsp;Yueh-Lin Chen,&nbsp;Jenn-Wei Chen,&nbsp;Shuying Wang,&nbsp;Pei-Jane Tsai,&nbsp;Jiunn-Jong Wu","doi":"10.1111/hel.70019","DOIUrl":"https://doi.org/10.1111/hel.70019","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>Helicobacter pylori</i> colonizes the human stomach as a dominant member of the gastric microbiota and constitutively expresses flagellar motility for survival. Carbon storage regulator A (CsrA) is a posttranscriptional global regulator and a critical determinant of <i>H. pylori</i>'s motility and pathogenicity. The regulation of <i>H. pylori</i> CsrA is still uncertain although in other species CsrA is reported to be antagonized by small RNAs and proteins. In this study, we attempted to unveil how CsrA is regulated and hypothesized that <i>H. pylori</i> CsrA activity is antagonized by a flagellar assembly factor, FliW2, via protein allosteric obstruction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Multiple sequence comparisons indicated that, along its length and in contrast to <i>fliW1</i>, the <i>fliW2</i> of <i>H. pylori</i> J99 is conserved. We then generated an isogenic Δ<i>fliW2</i> strain whose function was characterized using phenotypic and biochemical approaches. We also applied a machine learning approach (AlphaFold2) to predict FliW2-CsrA binding domains and investigated the FliW2-CsrA interaction using pull-down assays and in vivo bacterial two-hybrid systems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed the reduced expression of major flagellin FlaA and impaired flagellar filaments that attenuated the motility of the Δ<i>fliW2</i> strain. Furthermore, a direct interaction between FliW2 and CsrA was demonstrated, and a novel region of the C-terminal extension of CsrA was suggested to be crucial for CsrA interacting with FliW2. Based on our AlphaFold2 prediction, this C-terminal region of FliW2-CsrA interaction does not overlap with CsrA's N-terminal RNA binding domain, implying that FliW2 allosterically antagonizes CsrA activity and restricts CsrA's binding to <i>flaA</i> mRNAs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our data points to novel regulatory roles that the <i>H. pylori</i> flagellar assembly factor FliW2 has in obstructing CsrA activity, and thus FliW2 may indirectly antagonize CsrA's regulation of <i>flaA</i> mRNA processing and translation. Our findings reveal a new regulatory mechanism of flagellar motility in <i>H. pylori</i>.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hel.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Helicobacter pylori and Colorectal Cancer: Meeting Sir Austin Bradford Hill's Causality Criteria
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-03-10 DOI: 10.1111/hel.70024
Juan Sebastián Frías-Ordoñez, Arnoldo Riquelme, Hernando Marulanda-Fernandez, Lina Otero-Parra, José Augusto Urrego, Elder Otero-Ramos, José Darío Portillo-Miño, William Otero Regino

Introduction

Epidemiological and experimental studies have suggested that chronic H. pylori infection may be associated with colorectal cancer (CRC), a topic of growing interest. The Bradford-Hill criteria are the mainstay of the epidemiological approach to causal inference. We aim to evaluate the epidemiological evidence based on the Bradford-Hill causality criteria and the association between H. pylori and CRC.

Methodology

A literature review of the databases search: Pubmed, ScienceDirect, Embase, SciELO, Cochrane, and Medline. There are no limits in a period. Information sources that were coherent with the objectives set were selected.

Results

Applying the Bradford Hill criteria, we can conclude that H. pylori is positively associated with CRC. The current epidemiological findings should stimulate future studies to explain how H. pylori interacts with intestinal dysbiosis and the role of H. pylori eradication in the treatment and prevention of CRC.

Conclusions

H. pylori reasonably meets the Bradford Hill criteria for causality. Further studies are required to consolidate the data and generate strategies to determine whether H. pylori eradication translates into decreased CRC incidence and mortality in large populations.

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引用次数: 0
Global Population Structure, Virulence Factors and Antibiotic Resistance of Helicobacter pylori: A Pooled Analysis of 4067 Isolates From 76 Countries
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-03-09 DOI: 10.1111/hel.70025
Mengyi Zhu, Xianfeng Xu, Pengpeng Cai, Tianpei Wang, Meng Zhu, Caiwang Yan, Qianglong Pan, Chen Chen, Ying Wu, Guoxin Zhang, Guangfu Jin
<div> <section> <h3> Background</h3> <p><i>Helicobacter pylori</i> (<i>H. pylori</i>) is a common pathogen that has co-evolved with the human host for approximately 100,000 years; however, our understanding of its population structure remains limited. Furthermore, the detailed characteristics of its virulence factors and antibiotic resistance for <i>H. pylori</i> are not yet fully elucidated.</p> </section> <section> <h3> Methods</h3> <p>In this study, we curated a global genome dataset of 4067 <i>H. pylori</i> isolates from 76 countries and explored <i>H. pylori</i> characteristics, including population genetic structure, virulence factors, and antibiotic resistance. We used three approaches (fineSTRUCTURE, ADMIXTURE, and DAPC) to infer the population structure of <i>H. pylori</i>. We investigated the virulence of each isolate by calling genotypes of <i>cagA</i> and <i>vacA</i> and evaluated the correlations of virulence factors with subpopulation. For antibiotic resistance, we identified mutations to determine the genotypic antibiotic resistance. Then we estimated the prevalence of genotypic antibiotic resistance grouped by geographical location, subpopulation, and study period.</p> </section> <section> <h3> Result</h3> <p>We identified 21 subpopulations in 4067 <i>H. pylori</i> isolates, including 20 previously reported subpopulations and a novel subpopulation hspEuropeIsrael, and found that the population structure of <i>H. pylori</i> was geographically restricted. The novel subpopulation hspEuropeIsrael had a higher proportion of less virulent <i>cagA</i> and <i>vacA</i> genotypes compared to other subpopulations. After evaluating the rates of <i>H. pylori</i> genotypic resistance to four antibiotics, we found that the prevalence of genotypic resistance to amoxicillin and metronidazole was > 15% across all five continents. Genotypic resistance to levofloxacin was > 15% on all continents except for Oceania. Additionally, the genotypic resistance rate to clarithromycin was > 15% in Asia, Europe, and Oceania. A trend of increased genotypic resistance over time was observed in several continents during subgroup analyses. Furthermore, we constructed a comprehensive database for <i>H. pylori</i>, named <i>Helicobacter Pylori</i> Encyclopedia for Research (HELPER, http://ccra.njmu.edu.cn/helper).</p> </section> <section> <h3> Conclusion</h3> <p>Our results provide a detailed characterization of <i>H. pylori</i> and extend previous schemas. HELPER serves as an informative and comprehensive database that will be a valuable resource for researchers and lay the foundation for future studies on <i>H. pylori</i>.</p>
{"title":"Global Population Structure, Virulence Factors and Antibiotic Resistance of Helicobacter pylori: A Pooled Analysis of 4067 Isolates From 76 Countries","authors":"Mengyi Zhu,&nbsp;Xianfeng Xu,&nbsp;Pengpeng Cai,&nbsp;Tianpei Wang,&nbsp;Meng Zhu,&nbsp;Caiwang Yan,&nbsp;Qianglong Pan,&nbsp;Chen Chen,&nbsp;Ying Wu,&nbsp;Guoxin Zhang,&nbsp;Guangfu Jin","doi":"10.1111/hel.70025","DOIUrl":"https://doi.org/10.1111/hel.70025","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;&lt;i&gt;Helicobacter pylori&lt;/i&gt; (&lt;i&gt;H. pylori&lt;/i&gt;) is a common pathogen that has co-evolved with the human host for approximately 100,000 years; however, our understanding of its population structure remains limited. Furthermore, the detailed characteristics of its virulence factors and antibiotic resistance for &lt;i&gt;H. pylori&lt;/i&gt; are not yet fully elucidated.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In this study, we curated a global genome dataset of 4067 &lt;i&gt;H. pylori&lt;/i&gt; isolates from 76 countries and explored &lt;i&gt;H. pylori&lt;/i&gt; characteristics, including population genetic structure, virulence factors, and antibiotic resistance. We used three approaches (fineSTRUCTURE, ADMIXTURE, and DAPC) to infer the population structure of &lt;i&gt;H. pylori&lt;/i&gt;. We investigated the virulence of each isolate by calling genotypes of &lt;i&gt;cagA&lt;/i&gt; and &lt;i&gt;vacA&lt;/i&gt; and evaluated the correlations of virulence factors with subpopulation. For antibiotic resistance, we identified mutations to determine the genotypic antibiotic resistance. Then we estimated the prevalence of genotypic antibiotic resistance grouped by geographical location, subpopulation, and study period.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Result&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We identified 21 subpopulations in 4067 &lt;i&gt;H. pylori&lt;/i&gt; isolates, including 20 previously reported subpopulations and a novel subpopulation hspEuropeIsrael, and found that the population structure of &lt;i&gt;H. pylori&lt;/i&gt; was geographically restricted. The novel subpopulation hspEuropeIsrael had a higher proportion of less virulent &lt;i&gt;cagA&lt;/i&gt; and &lt;i&gt;vacA&lt;/i&gt; genotypes compared to other subpopulations. After evaluating the rates of &lt;i&gt;H. pylori&lt;/i&gt; genotypic resistance to four antibiotics, we found that the prevalence of genotypic resistance to amoxicillin and metronidazole was &gt; 15% across all five continents. Genotypic resistance to levofloxacin was &gt; 15% on all continents except for Oceania. Additionally, the genotypic resistance rate to clarithromycin was &gt; 15% in Asia, Europe, and Oceania. A trend of increased genotypic resistance over time was observed in several continents during subgroup analyses. Furthermore, we constructed a comprehensive database for &lt;i&gt;H. pylori&lt;/i&gt;, named &lt;i&gt;Helicobacter Pylori&lt;/i&gt; Encyclopedia for Research (HELPER, http://ccra.njmu.edu.cn/helper).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our results provide a detailed characterization of &lt;i&gt;H. pylori&lt;/i&gt; and extend previous schemas. HELPER serves as an informative and comprehensive database that will be a valuable resource for researchers and lay the foundation for future studies on &lt;i&gt;H. pylori&lt;/i&gt;.&lt;/p&gt;\u0000 ","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Helicobacter
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