{"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, Yao-Yao Li, 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}
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.
{"title":"Innate Immunity in Helicobacter pylori Infection and Gastric Oncogenesis","authors":"Yuheng Zhang, Zhiyu Yan, Yuhao Jiao, Yunlu Feng, Shengyu Zhang, 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}
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, Benjamin Dickins, Fang Yie Kiang, Wei-Jiun Tsai, Yueh-Lin Chen, Jenn-Wei Chen, Shuying Wang, Pei-Jane Tsai, 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}
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.
{"title":"Helicobacter pylori and Colorectal Cancer: Meeting Sir Austin Bradford Hill's Causality Criteria","authors":"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","doi":"10.1111/hel.70024","DOIUrl":"https://doi.org/10.1111/hel.70024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Epidemiological and experimental studies have suggested that chronic <i>H. pylori</i> 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 <i>H. pylori</i> and CRC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Applying the Bradford Hill criteria, we can conclude that <i>H. pylori</i> is positively associated with CRC. The current epidemiological findings should stimulate future studies to explain how <i>H. pylori</i> interacts with intestinal dysbiosis and the role of <i>H. pylori</i> eradication in the treatment and prevention of CRC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p><i>H. pylori</i> reasonably meets the Bradford Hill criteria for causality. Further studies are required to consolidate the data and generate strategies to determine whether <i>H. pylori</i> eradication translates into decreased CRC incidence and mortality in large populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581814","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}
<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, Xianfeng Xu, Pengpeng Cai, Tianpei Wang, Meng Zhu, Caiwang Yan, Qianglong Pan, Chen Chen, Ying Wu, Guoxin Zhang, Guangfu Jin","doi":"10.1111/hel.70025","DOIUrl":"https://doi.org/10.1111/hel.70025","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <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>\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}
Helicobacter pylori (H. pylori) has been identified as a type I carcinogen and contributes to a high rate of gastric cancer (GC), especially in Eastern Asia. Extracellular vesicles (EVs) have the potential to be used to detect various cancer types and diseases. However, the protein markers in EVs for the prognosis of H. pylori infection and GC are unknown. We aim to identify the proteins within EVs derived from a gastric epithelial cell line (AGS) infected with H. pylori by using LC-MS/MS.
Materials and Methods
EVs were isolated from AGS cells infected with high- and low-virulence H. pylori (strains TN2wt and Tx30a) by ultracentrifugation. Proteins within these EVs were identified and analyzed for potential marker candidates through bioinformatics. Proteins in H. pylori-derived EVs (HpEVs) from bacterial culture supernatant and HpEVs derived from H. pylori-infected AGS cells were elucidated.
Results
Differentially expressed proteins by proteomic analysis in AGSEVs-Tx30a vs. AGSEVs-noninfected (NI) and AGSEVs-TN2wt vs. AGSEVs-NI were 107 and 55 proteins, respectively. Bioinformatics of these proteomes revealed that essential proteins for H. pylori survival and pathogenicity including outer membrane proteins, metabolism-related, host cell infection-related, and virulence-related proteins were observed in HpEVs. Interestingly, EVs derived from AGS cells infected with H. pylori TN2wt significantly contained multiple proteins related to GC (ATP6V0A1, GAPDH, HINT1, LYZ, and RBX1).
Conclusion
This study provides a comprehensive protein profile of EVs from H. pylori-infected AGS cells and HpEVs, which could serve as liquid-based biomarkers in the future for screening H. pylori infection, especially GC-related.
{"title":"Proteomic Profiling of Extracellular Vesicles Reveals Potential Biomarkers for Helicobacter pylori Infection and Gastric Cancer","authors":"Phawinee Subsomwong, Krisana Asano, Junko Akada, Takashi Matsumoto, Akio Nakane, Yoshio Yamaoka","doi":"10.1111/hel.70022","DOIUrl":"https://doi.org/10.1111/hel.70022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>Helicobacter pylori</i> (<i>H. pylori</i>) has been identified as a type I carcinogen and contributes to a high rate of gastric cancer (GC), especially in Eastern Asia. Extracellular vesicles (EVs) have the potential to be used to detect various cancer types and diseases. However, the protein markers in EVs for the prognosis of <i>H. pylori</i> infection and GC are unknown. We aim to identify the proteins within EVs derived from a gastric epithelial cell line (AGS) infected with <i>H. pylori</i> by using LC-MS/MS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>EVs were isolated from AGS cells infected with high- and low-virulence <i>H. pylori</i> (strains TN2wt and Tx30a) by ultracentrifugation. Proteins within these EVs were identified and analyzed for potential marker candidates through bioinformatics. Proteins in <i>H. pylori-</i>derived EVs (HpEVs) from bacterial culture supernatant and HpEVs derived from <i>H. pylori</i>-infected AGS cells were elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Differentially expressed proteins by proteomic analysis in AGSEVs-Tx30a vs. AGSEVs-noninfected (NI) and AGSEVs-TN2wt vs. AGSEVs-NI were 107 and 55 proteins, respectively. Bioinformatics of these proteomes revealed that essential proteins for <i>H. pylori</i> survival and pathogenicity including outer membrane proteins, metabolism-related, host cell infection-related, and virulence-related proteins were observed in HpEVs. Interestingly, EVs derived from AGS cells infected with <i>H. pylori</i> TN2wt significantly contained multiple proteins related to GC (ATP6V0A1, GAPDH, HINT1, LYZ, and RBX1).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides a comprehensive protein profile of EVs from <i>H. pylori</i>-infected AGS cells and HpEVs, which could serve as liquid-based biomarkers in the future for screening <i>H. pylori</i> infection, especially GC-related.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hel.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533388","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}
Mohammed Awadh Abdun, Lu Xu, Xiao-Ting Li, Amr Mekky, Maher Al Hussan, Ezaldin M. I. Abuheit, Chen Zhang, Ishtiaq Ur Rahman, Miao Yu, Hafiz Muhammad Sohail Sarwar, Bin-Bin Yan, Jia-Bei Xie, Bo-Wei Liu, Song-Ze Ding
Background
Helicobacter pylori (H. pylori) is the major cause of gastric mucosal precancerous lesions in adulthood, but its impact on pediatric patients remains unclear. We aimed to investigate H. pylori-induced gastric precancerous lesions in children and adolescents globally and analyze their influencing factors for related disease management and prevention.
Materials and Methods
We conducted a comprehensive literature search in major databases to identify studies including pediatric patients with gastric precancerous lesions and H. pylori infection status. Prevalence rates were computed using random-effects or fixed-effect models. A stratified analysis was conducted based on location, age, universal health coverage (UHC), and publication time.
Results
Among the 3359 relevant articles screened, 24 studies (7036 participants) met the inclusion criteria. The overall prevalence of precancerous lesions in H. pylori-infected patients was 17.2%, in which atrophic gastritis (AG) and intestinal metaplasia (IM) were 13.5% and 3.6%, respectively. Precancerous lesion rates in infected individuals across different regions were as follows: Africa at 33.8% (AG: 32.6%), Latin America at 22.1% (AG: 17.9%, IM: 4.0%), Asia at 18.1% (AG: 12.4%, IM: 4.4%, Dysplasia: 1.2%), and Europe at 6.3% (AG: 4.3%, IM: 1.7%). Infected adolescents (> 10 years) exhibited a higher prevalence of precancerous lesions than younger children (≤ 10 years) at 14.2% (AG: 9.7%, IM: 2.9%) versus 3.4% (AG: 2.3%, IM: 1.1%), respectively. The prevalence of precancerous lesions in infected patients was higher in areas with low-medium UHC compared with high UHC (24.0% vs. 12.5%).
Conclusions
H. pylori infection causes significant gastric mucosal precancerous lesions in pediatric patients, representing a major concern for this population and a previously neglected area. Future in-depth investigations and proper management for related disease prevention are warranted.
{"title":"Global Prevalence of Helicobacter pylori Infection-Associated Gastric Preneoplastic Lesions in Pediatric Patients: A Systematic Review and Meta-Analysis","authors":"Mohammed Awadh Abdun, Lu Xu, Xiao-Ting Li, Amr Mekky, Maher Al Hussan, Ezaldin M. I. Abuheit, Chen Zhang, Ishtiaq Ur Rahman, Miao Yu, Hafiz Muhammad Sohail Sarwar, Bin-Bin Yan, Jia-Bei Xie, Bo-Wei Liu, Song-Ze Ding","doi":"10.1111/hel.70021","DOIUrl":"https://doi.org/10.1111/hel.70021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>Helicobacter pylori</i> (<i>H. pylori</i>) is the major cause of gastric mucosal precancerous lesions in adulthood, but its impact on pediatric patients remains unclear. We aimed to investigate <i>H. pylori</i>-induced gastric precancerous lesions in children and adolescents globally and analyze their influencing factors for related disease management and prevention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We conducted a comprehensive literature search in major databases to identify studies including pediatric patients with gastric precancerous lesions and <i>H. pylori</i> infection status. Prevalence rates were computed using random-effects or fixed-effect models. A stratified analysis was conducted based on location, age, universal health coverage (UHC), and publication time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 3359 relevant articles screened, 24 studies (7036 participants) met the inclusion criteria. The overall prevalence of precancerous lesions in <i>H. pylori</i>-infected patients was 17.2%, in which atrophic gastritis (AG) and intestinal metaplasia (IM) were 13.5% and 3.6%, respectively. Precancerous lesion rates in infected individuals across different regions were as follows: Africa at 33.8% (AG: 32.6%), Latin America at 22.1% (AG: 17.9%, IM: 4.0%), Asia at 18.1% (AG: 12.4%, IM: 4.4%, Dysplasia: 1.2%), and Europe at 6.3% (AG: 4.3%, IM: 1.7%). Infected adolescents (> 10 years) exhibited a higher prevalence of precancerous lesions than younger children (≤ 10 years) at 14.2% (AG: 9.7%, IM: 2.9%) versus 3.4% (AG: 2.3%, IM: 1.1%), respectively. The prevalence of precancerous lesions in infected patients was higher in areas with low-medium UHC compared with high UHC (24.0% vs. 12.5%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p><i>H. pylori</i> infection causes significant gastric mucosal precancerous lesions in pediatric patients, representing a major concern for this population and a previously neglected area. Future in-depth investigations and proper management for related disease prevention are warranted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p> PROSPERO number: CRD42023424683</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513631","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}
Harriet J. Giddings, Ana Teodósio, Jordanne Jones, Jack L. McMurray, Kelly Hunter, Riad Alame, Isaac Gardiner, Zainab Abdawn, William Butterworth, Ian R. Henderson, Jeffrey A. Cole, Claire D. Shannon-Lowe, Amanda E. Rossiter-Pearson
Background
Stomach cancer is the fourth leading cause of cancer-related deaths worldwide. Helicobacter pylori is the main risk factor for gastric adenocarcinoma (GAC), yet the precise mechanism underpinning this association remains controversial. Gastric intestinal metaplasia (GIM) represents the precancerous stage and follows H. pylori-associated chronic gastritis (CG). Sequencing studies have revealed fewer H. pylori and more non-H. pylori bacteria in GAC. However, the spatial organization of the gastric microbiota in health and disease is unknown.
Materials and Methods
Here, we have combined RNA in situ hybridization and immunohistochemistry to detect H. pylori, non-H. pylori bacteria, and host cell markers (E-cadherin, Mucins 5AC and 2) on tissue sections from patients with CG (n = 15) and GIM (n = 17).
Results
Quantitative analysis of whole slide scans revealed significant correlations of H. pylori and other bacteria in CG and GIM. In contrast to sequencing studies, significantly fewer non-H. pylori bacteria were detected in H. pylori-negative patients. Importantly, whilst H. pylori exclusively colonized the gastric glands, non-H. pylori bacteria invaded the lamina propria in 6/9 CG and 8/10 GIM H. pylori-positive patients. A rapid and cost-effective modified Gram stain was used to confirm these findings and enabled detection of non-H. pylori bacteria in GIM samples.
Conclusions
The invasion of the gastric lamina propria by non-H. pylori bacteria during H. pylori-associated CG and GIM represents an overlooked phenomenon in cancer progression. Further work must determine the mechanisms underlying the synergistic roles of H. pylori and other bacteria in carcinogenesis. This observation should redirect attempts to prevent, diagnose, and treat GAC.
{"title":"The Gastric Microbiota Invade the Lamina Propria in Helicobacter pylori-Associated Gastritis and Precancer","authors":"Harriet J. Giddings, Ana Teodósio, Jordanne Jones, Jack L. McMurray, Kelly Hunter, Riad Alame, Isaac Gardiner, Zainab Abdawn, William Butterworth, Ian R. Henderson, Jeffrey A. Cole, Claire D. Shannon-Lowe, Amanda E. Rossiter-Pearson","doi":"10.1111/hel.70016","DOIUrl":"https://doi.org/10.1111/hel.70016","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Stomach cancer is the fourth leading cause of cancer-related deaths worldwide. <i>Helicobacter pylori</i> is the main risk factor for gastric adenocarcinoma (GAC), yet the precise mechanism underpinning this association remains controversial. Gastric intestinal metaplasia (GIM) represents the precancerous stage and follows <i>H. pylori-</i>associated chronic gastritis (CG). Sequencing studies have revealed fewer <i>H. pylori</i> and more non-<i>H. pylori</i> bacteria in GAC. However, the spatial organization of the gastric microbiota in health and disease is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Here, we have combined RNA in situ hybridization and immunohistochemistry to detect <i>H. pylori,</i> non-<i>H. pylori</i> bacteria, and host cell markers (E-cadherin, Mucins 5AC and 2) on tissue sections from patients with CG (<i>n</i> = 15) and GIM (<i>n</i> = 17).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Quantitative analysis of whole slide scans revealed significant correlations of <i>H. pylori</i> and other bacteria in CG and GIM. In contrast to sequencing studies, significantly fewer non-<i>H. pylori</i> bacteria were detected in <i>H. pylori-</i>negative patients. Importantly, whilst <i>H. pylori</i> exclusively colonized the gastric glands, non-<i>H. pylori</i> bacteria invaded the lamina propria in 6/9 CG and 8/10 GIM <i>H. pylori</i>-positive patients. A rapid and cost-effective modified Gram stain was used to confirm these findings and enabled detection of non-<i>H. pylori</i> bacteria in GIM samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The invasion of the gastric lamina propria by non-<i>H. pylori</i> bacteria during <i>H. pylori-</i>associated CG and GIM represents an overlooked phenomenon in cancer progression. Further work must determine the mechanisms underlying the synergistic roles of <i>H. pylori</i> and other bacteria in carcinogenesis. This observation should redirect attempts to prevent, diagnose, and treat GAC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hel.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497391","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}
We aimed to assess the effects of Helicobacter pylori (H. pylori) eradication on the rebound of reflux-related symptoms among gastroesophageal reflux disease (GERD) patients.
Methods
This prospective randomized study recruited patients with typical reflux symptoms and reflux esophagitis on esophagogastroduodenoscopy (NCT02934152). Patients positive for H. pylori via a urea breath test (UBT) were randomly assigned to receive bacterial eradication with triple therapy for 2 weeks either before or after proton-pump inhibitor (PPI) treatment for 4 weeks. Follow-up was implemented with serial GerdQ evaluation and a subsequent UBT. The primary outcome was the incidence rates of symptom rebound between patients with and without H. pylori infection. The secondary outcomes included the severity of symptom rebound, incidence rates of symptom rebound, and successful eradication rates between the early and late eradication groups.
Results
A total of 248 patients were enrolled, of whom 107 (43.1%) tested positive for H. pylori infection. All patients with and without concurrent H. pylori infection had significant symptom improvement over the entire treatment. Patients with H. pylori infection had significantly lower rates of symptom rebound (19.8% vs. 34.2%, p = 0.034) and rebound severity (1.8 ± 0.7 vs. 2.8 ± 1.6, p = 0.031) 4 weeks after eradication and PPI treatment than those without. The incidence rates of symptom rebound and successful eradication rates were not significantly different between the early and late eradication groups.
Conclusions
GERD patients with concurrent H. pylori infection were less susceptible to symptom rebound after H. pylori eradication compared to those without.
Trial Registration
ClinicalTrial.gov (NCT02934152)
背景/目的我们旨在评估幽门螺杆菌根除对胃食管反流病（GERD）患者反流相关症状反弹的影响。方法本前瞻性随机研究招募食管胃十二指肠镜检查有典型反流症状和反流性食管炎的患者（NCT02934152）。通过尿素呼气试验（UBT）检测幽门螺杆菌阳性的患者被随机分配在质子泵抑制剂（PPI）治疗4周之前或之后接受2周的细菌根除三联疗法。通过连续GerdQ评估和随后的UBT进行随访。主要观察指标是有无幽门螺杆菌感染的患者之间症状反弹的发生率。次要结局包括症状反弹的严重程度、症状反弹的发生率以及早期和晚期根除组之间的根除成功率。结果共纳入248例患者，其中幽门螺杆菌感染阳性107例（43.1%）。所有合并或不合并幽门螺杆菌感染的患者在整个治疗过程中症状均有显著改善。幽门螺杆菌感染患者在根除和PPI治疗4周后症状反跳率（19.8% vs. 34.2%, p = 0.034）和反跳严重程度（1.8±0.7 vs. 2.8±1.6,p = 0.031）显著低于未治疗的患者。症状反弹发生率和根除成功率在早期和晚期根除组之间无显著差异。结论伴有幽门螺杆菌感染的胃食管反流患者在根除幽门螺杆菌后较未感染幽门螺杆菌的患者更不易出现症状反弹。临床试验注册网站（NCT02934152）
{"title":"Rebound of Reflux-Related Symptoms After Helicobacter pylori Eradication in Patients With Gastroesophageal Reflux Disease: A Prospective Randomized Study","authors":"Kai-Yu Hu, Ping-Huei Tseng, Jyh-Ming Liou, Chia-Hung Tu, Chien-Chuan Chen, Yi-Chia Lee, Han-Mo Chiu, Ming-Shiang Wu","doi":"10.1111/hel.70023","DOIUrl":"https://doi.org/10.1111/hel.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/Purpose</h3>\u0000 \u0000 <p>We aimed to assess the effects of <i>Helicobacter pylori</i> (<i>H. pylori</i>) eradication on the rebound of reflux-related symptoms among gastroesophageal reflux disease (GERD) patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective randomized study recruited patients with typical reflux symptoms and reflux esophagitis on esophagogastroduodenoscopy (NCT02934152). Patients positive for <i>H. pylori</i> via a urea breath test (UBT) were randomly assigned to receive bacterial eradication with triple therapy for 2 weeks either before or after proton-pump inhibitor (PPI) treatment for 4 weeks. Follow-up was implemented with serial GerdQ evaluation and a subsequent UBT. The primary outcome was the incidence rates of symptom rebound between patients with and without <i>H. pylori</i> infection. The secondary outcomes included the severity of symptom rebound, incidence rates of symptom rebound, and successful eradication rates between the early and late eradication groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 248 patients were enrolled, of whom 107 (43.1%) tested positive for <i>H. pylori</i> infection. All patients with and without concurrent <i>H. pylori</i> infection had significant symptom improvement over the entire treatment. Patients with <i>H. pylori</i> infection had significantly lower rates of symptom rebound (19.8% vs. 34.2%, <i>p</i> = 0.034) and rebound severity (1.8 ± 0.7 vs. 2.8 ± 1.6, <i>p</i> = 0.031) 4 weeks after eradication and PPI treatment than those without. The incidence rates of symptom rebound and successful eradication rates were not significantly different between the early and late eradication groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>GERD patients with concurrent <i>H. pylori</i> infection were less susceptible to symptom rebound after <i>H. pylori</i> eradication compared to those without.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrial.gov (NCT02934152)</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490049","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}
Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) that offers several advantages, such as fast onset time and strong acid inhibition, in the treatment of Helicobacter pylori infection. This study aims to evaluate the efficacy, adverse reactions, and compliance of the 14-day vonoprazan-amoxicillin dual therapy versus drug sensitivity-based individualized therapy in the retreatment of H. pylori infection.
Methods
This multicenter, open-label, randomized, controlled non-inferiority study enrolled 240 adult patients who previously failed anti-H. pylori treatment. These patients were randomly assigned to receive the 14-day vonoprazan-amoxicillin dual therapy or drug sensitivity-based individualized therapy. The primary outcome was the eradication rate, and the secondary outcomes mainly included adverse events, patient compliance, antibiotic resistance rates, and risk factors that affected the eradication rate.
Results
The intention-to-treat (ITT) and per-protocol (PP) analyses revealed that the eradication rates for the vonoprazan-amoxicillin dual therapy and drug sensitivity-based individualized therapy were comparably high, with rates of 87.50% and 83.33%, respectively. Furthermore, the vonoprazan-amoxicillin dual therapy fulfilled the criteria for the non-inferiority test, when compared to individualized therapy. The incidence of adverse reactions was significantly lower in the vonoprazan-amoxicillin dual therapy group. Both groups showed similarly good compliance and comparable rates of antibiotic resistance. The previous treatment with a clarithromycin-containing regimen was identified as an independent risk factor for clarithromycin resistance.
Conclusion
The 14-day vonoprazan-amoxicillin dual therapy exhibits high eradication rates and low incidence of adverse reactions in retreated patients, indicating its effectiveness and safety as a rescue regimen for patients with H. pylori infection.
{"title":"Vonoprazan-Amoxicillin Dual Therapy Versus Drug Sensitivity-Based Individualized Therapy as a Rescue Regimen for Helicobacter pylori Infection: A Multicenter, Randomized Controlled Trial","authors":"Yu-xiang Liu, Han-ning Liu, Heng-qi Liu, Ying-ying Yang, Hong-li Cui, Li-lin Fan, Wen-jing Sun, Hao Mei, Xing-wei Wang, Guo Yan, Chun-hui Lan","doi":"10.1111/hel.70009","DOIUrl":"https://doi.org/10.1111/hel.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) that offers several advantages, such as fast onset time and strong acid inhibition, in the treatment of <i>Helicobacter pylori</i> infection. This study aims to evaluate the efficacy, adverse reactions, and compliance of the 14-day vonoprazan-amoxicillin dual therapy versus drug sensitivity-based individualized therapy in the retreatment of <i>H. pylori</i> infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This multicenter, open-label, randomized, controlled non-inferiority study enrolled 240 adult patients who previously failed anti-<i>H. pylori</i> treatment. These patients were randomly assigned to receive the 14-day vonoprazan-amoxicillin dual therapy or drug sensitivity-based individualized therapy. The primary outcome was the eradication rate, and the secondary outcomes mainly included adverse events, patient compliance, antibiotic resistance rates, and risk factors that affected the eradication rate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The intention-to-treat (ITT) and per-protocol (PP) analyses revealed that the eradication rates for the vonoprazan-amoxicillin dual therapy and drug sensitivity-based individualized therapy were comparably high, with rates of 87.50% and 83.33%, respectively. Furthermore, the vonoprazan-amoxicillin dual therapy fulfilled the criteria for the non-inferiority test, when compared to individualized therapy. The incidence of adverse reactions was significantly lower in the vonoprazan-amoxicillin dual therapy group. Both groups showed similarly good compliance and comparable rates of antibiotic resistance. The previous treatment with a clarithromycin-containing regimen was identified as an independent risk factor for clarithromycin resistance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The 14-day vonoprazan-amoxicillin dual therapy exhibits high eradication rates and low incidence of adverse reactions in retreated patients, indicating its effectiveness and safety as a rescue regimen for patients with <i>H. pylori</i> infection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481386","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}
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