ABSTRACT Background oipA , an outer membrane protein of Helicobacter pylori , is linked to IL‐8 induction and gastric inflammation, but its role is debated due to inconsistent findings. This study aims to explore the role of oipA phase variation in modulating the virulence traits of H. pylori , a bacterium strongly associated with the development of gastric cancer. Material and Methods American clinical isolate AH868 strain for naturally occurring phase variations of the oipA gene, and G27 strain for in vitro–induced phase variations were used to elucidate oipA 's impact on key virulence phenotypes, including cell elongation, CagA phosphorylation, and IL‐8 induction. Results Using AH868 strain, natural oipA phase variation does not affect cell elongation and IL‐8 induction. Interestingly, however, in vitro–induced oipA phase variations in G27 strain uncovered that 9.4% of oipA “Off” transformants exhibit reduced cell elongation while all maintaining consistent IL‐8 induction levels. Additionally, complementation of oipA “Off to On” status restores the cell elongation phenotype in 12.5% of transformants, highlighting the importance of oipA in maintaining normal cell morphology. Crucially, these variations in cell elongation are not linked to changes in bacterial adherence capabilities. Furthermore, the study shows a correlation among oipA phase variation, cell elongation, and CagA phosphorylation, suggesting that oipA influences the functionality of the Type IV secretion system. Whole‐genome sequencing of selected transformants reveals genetic variations in bab paralogue, cagY gene, and other genomic regions, underscoring the complex genetic interactions that shape H. pylori 's virulence. Conclusions Our research provides new insights into the subtle yet significant role of oipA phase variation in H. pylori pathogenicity, emphasizing the need for further studies to explore the intricate molecular mechanisms involved. This understanding could pave the way for targeted therapeutic strategies to mitigate the impact of H. pylori on human health.

Jing Lai

Sacheera Angulmaduwa

Myeong‐A Kim

Aeryun Kim

Kavinda Tissera

Yong‐Joon Cho

Jeong‐Heon Cha

Helicobacter

Influence of <scp>oipA</scp> Phase Variation on Virulence Phenotypes Related to Type <scp>IV</scp> Secretion System in Helicobacter pylori

oipA 相变对 Helicobacter pylori 中与IV型分泌系统相关的毒力表型的影响

ABSTRACT Background The eradication of Helicobacter pylori ( H. pylori ) is crucial due to its rising prevalence and increasing resistance. Bismuth‐containing quadruple therapies (BcQTs) have been proposed as a viable treatment option; however, the optimal duration for it remains contentious. This systematic review and meta‐analysis aimed to compare the clinical efficacy of short‐term BcQT (defined as 7 or 10 days) with a standard 14‐day course. Methods A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted for randomized controlled trials published in English until June 20, 2024. Eligibility criteria were applied to identify relevant studies. Summary risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for the included studies regarding eradication rates, adverse effects, and compliance. This systematic review and meta‐analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement and was previously registered in PROSPERO under registration number CRD42024547773. Results This meta‐analysis finally included 15 trials involving a total of 4505 patients. The eradication rates for short courses of BcQT were lower than those for the 14‐day course (RR 0.96, 95% CI 0.93–0.99). However, the eradication rate for the 10‐day therapy was comparable to that of the 14‐day therapy (RR 0.98, 95% CI 0.95–1.00). Subgroup analyses of antibiotic combinations indicated that tetracycline and metronidazole combinations yielded similar H. pylori eradication rates in the 7‐day versus the 14‐day BcQT (RR 0.93, 95% CI 0.84–1.02). In the potassium‐competitive acid blocker subgroup, the eradication rates remained similar across the 14‐day group and the short‐course treatment groups, whether evaluating the short‐term treatment groups as a whole or the 7‐ and 10‐day subgroups separately. Additionally, the adverse effects and compliance associated with the short course of BcQT were comparable to those of the 14‐day therapy. Conclusion A 10‐day course of BcQT may represent the optimal treatment duration. Nevertheless, the choice of antibiotic combination should be guided by the regional antibiotic resistance patterns of H. pylori , as combinations with lower resistance rates are more effective. Trial Registration PROSPERO number: CRD42024547773

Miao Duan

Qingzhou Kong

Hui Wang

Yueyue Li

Optimal Duration of Bismuth‐Containing Quadruple Therapy for Helicobacter pylori Eradication: A Systematic Review and Meta‐Analysis

含铋四联疗法根除幽门螺杆菌的最佳疗程：一项系统综述和Meta分析

ABSTRACT Background Treatment with potassium‐competitive acid blockers has shown acceptable efficacy in Helicobacter pylori eradication. In regions like Korea, where the clarithromycin resistance rate is high, alternative combinations like non‐bismuth quadruple therapies have shown favorable results. This study compared the outcomes of sequential eradication therapy with new potassium‐competitive acid blocker tegoprazan and conventional esomeprazole‐containing sequential therapy. Materials and Methods Patients with Helicobacter pylori ( H. pylori ) infection were consecutively recruited. Patients were allocated to either an esomeprazole‐containing sequential or a tegoprazan‐containing sequential therapy group. Sequential therapy comprised esomeprazole (40 mg) or tegoprazan (50 mg) plus amoxicillin (1000 mg) twice daily for the initial 5 days, followed by esomeprazole (40 mg) or tegoprazan (50 mg) with clarithromycin (500 mg) and metronidazole (500 mg) twice daily for the remaining 5 days. Eradication rate, compliance, and adverse events were recorded. Results A total of 406 patients with H. pylori infection were enrolled in the trial and analyzed per protocol. Eradication rate by intention‐to‐treat and per‐protocol was 83.8% (95% confidence interval [CI]: 78.7–88.9) for esomeprazole‐containing sequential therapy, and 87.1% (95% CI: 82.5–91.8) for tegoprazan‐containing sequential therapy, with no statistical significance ( p = 0.399). Additionally, there was no statistically significant difference in treatment compliance between the two groups. Nausea was more prevalent (23.3%, 27/202) with sequential tegoprazans than with esomeprazole‐containing sequential therapy (14.2%, 29/204; p = 0.022). Conclusion Tegoprazan‐containing 10‐day sequential eradication treatment demonstrated similar eradication efficacy compared to esomeprazole‐containing treatment, even in regions with high antimicrobial resistance, such as Korea. Trial Registration ClinicalTrials.gov : NCT06382493

Jung Won Lee

Nayoung Kim

Jongchan Lee

So Young Jo

Dong Ho Lee

Efficacy of Tegoprazan‐Containing Sequential Eradication Treatment Compared to Esomeprazole‐Containing Sequential Eradication of Helicobacter pylori in South Korea, a Region With High Antimicrobial Resistance: A Prospective, Randomized, Single Tertiary Center Study

含泰妥拉唑序贯根除治疗与含埃索美拉唑序贯根除治疗在韩国的疗效比较：一项针对高耐药性地区的前瞻性、随机、单中心研究

In the eradication of Helicobacter pylori, the efficacy of bismuth remains inconclusive. We aimed to compare the efficacy of bismuth on various H. pylori eradication regimens.

A Reum Choe

Chung Hyun Tae

Miyoung Choi

Ki‐Nam Shim

Hye‐Kyung Jung

Systematic Review and Meta‐Analysis: Bismuth Enhances the Efficacy for Eradication of Helicobacter pylori

系统评价与荟萃分析：铋剂增强根除幽门螺杆菌的疗效

To evaluate the efficacy of colloidal bismuth subcitrate (CBS) therapy for the eradication of H. pylori in patients from a national pediatric registry of H. pylori infection.

Gonzalo Botija

Gonzalo Galicia

Beatriz Martínez

Carmen Cuadrado

Marta Soria

Sonia Fernández

Pedro Urruzuno

María‐Luz Cilleruelo

Efficacy of Bismuth Therapy in Eradicating Helicobacter pylori in Children—Data From the <scp>RENIHp</scp> Registry

铋剂疗法在儿童中根除幽门螺杆菌的有效性——来自<scp>RENIHp</scp>登记库的数据

Abstract Background Flagella‐mediated motility is both a crucial virulence determinant of Helicobacter pylori and a factor associated with gastrointestinal diseases. Flagellar formation requires flagellins to be glycosylated with pseudaminic acid (Pse), a process that has been extensively studied. However, the transfer of Pse to flagellins remains poorly understood. Therefore, the aim of this study is to characterize a putative glycosyltransferase jhp0106 in flagellar formation. Materials and Methods Western blotting and chemical deglycosylation were performed to examine FlaA glycosylation. Protein structural analyses were executed to identify the active site residues of Jhp0106, while the Jhp0106‐FlaA interaction was examined using a bacterial two‐hybrid assay. Lastly, site‐directed mutants with mutated active site residues in the jhp0106 gene were generated and investigated using a motility assay, Western blotting, cDNA‐qPCR analysis, and electron microscopic examination. Results Loss of flagellar formation in the Δ jhp0106 mutant was confirmed to be associated with non‐glycosylated FlaA. Furthermore, three active site residues of Jhp0106 (S350, F376, and E415) were identified within a potential substrate‐binding region. The interaction between FlaA and Jhp0106, Jhp0106::S350A, Jhp0106::F376A, or Jhp0106::E415A was determined to be significant. As well, the substitution of S350A, F376A, or E415A in the site‐directed Δ jhp0106 mutants resulted in impaired motility, deficient FlaA glycosylation, and lacking flagella. However, these phenotypic changes were regardless of flaA expression, implying an indefinite proteolytic degradation of FlaA occurred. Conclusions This study demonstrated that Jhp0106 (PseE) binds to FlaA mediating FlaA glycosylation and flagellar formation. Our discovery of PseE has revealed a new glycosyltransferase family responsible for flagellin glycosylation in pathogens.

Kai‐Yuan Yang

Cheng‐Yen Kao

Marcia Shu‐Wei Su

Shuying Wang

Yueh‐Lin Chen

Shiau‐Ting Hu

Jenn‐Wei Chen

Ching‐Hao Teng

Pei‐Jane Tsai

Jiunn‐Jong Wu

Glycosyltransferase Jhp0106 (PseE) contributes to flagellin maturation in Helicobacterpylori

糖基转移酶Jhp0106（PseE）参与幽门螺杆菌鞭毛蛋白成熟

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Z. Kaouah

J. Buyck

M. Pichon

C. Burucoa

L. Prouvensier

J. Moreau

S. Marchand

N. Gregoire

J. Cremniter

Concentration‐dependent effect of amoxicillin against clinical strains of Helicobacter pylori

阿莫西林对临床幽门螺杆菌菌株的浓度依赖性效应

Abstract Background Helicobacter pylori infection is primarily acquired in childhood and can lead to peptic ulcer diseases and gastric cancer. The prevalence of H. pylori infection varies widely in different countries. The aim of this study was to explore the change of pediatric H. pylori seroprevalence in the past two decades and to investigate the risk factors for pediatric H. pylori seropositivity in southern Taiwan. Materials and Methods This study enrolled children aged 7–12 years in Tainan City in 2018 and compared the result with our previous data in 1998, 2005, and 2010. Parents of the participants were invited to fill out questionnaires, including information of personal history, family history of peptic ulcer diseases, annual household income, and source of drinking water. Blood samples were analyzed for anti‐ H. pylori IgG by enzyme‐linked immunosorbent assay. Results A total of 391, 629, 618, and 488 elementary school students in Tainan City were enrolled in 1998, 2005, 2010, and 2018, respectively. There was a significant decline in H. pylori seroprevalence from 9.2% in 1998, 7.8% in 2005, 6.2% in 2010 to 4.7% in 2018 ( p &lt; 0.001). Neither gender difference nor age difference was found in H. pylori seropositivity in each year of enrollment. Low household income was significantly associated with pediatric H. pylori seropositivity. Conclusions The seroprevalence of H. pylori infection among elementary schoolchildren has remarkably declined in southern Taiwan in the past two decades. Low household income was a risk factor for pediatric H. pylori seropositivity.

Hsiao‐Yu Lo

Yao‐Jong Yang

Seroprevalence of Helicobacter pylori infection among schoolchildren in southern Taiwan—A 20‐year longitudinal follow‐up

台湾南部学童幽门螺杆菌感染的血清流行率——一项20年的纵向随访研究

Abstract Background Helicobacter species (spp.) have been detected in human bile and hepatobiliary tissue Helicobacter spp. promote gallstone formation and hepatobiliary tumors in laboratory studies, though it remains unclear whether Helicobacter spp. contribute to these cancers in humans. We used a multiplex panel to assess whether seropositivity to Helicobacter (H.) hepaticus or H. bilis proteins was associated with the development of hepatobiliary cancers in the Finnish Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study, and US‐based Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Methods We included 62 biliary and 121 liver cancers, and 190 age‐matched controls from ATBC and 74 biliary and 105 liver cancers, and 364 age‐ and sex‐matched controls from PLCO. Seropositivity to 14 H. hepaticus and H. bilis antigens was measured using a multiplex assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for major hepatobiliary cancer risk factors and Helicobacter pylori serostatus. Results Seropositivity to the H . bilis antigen, P167D, was associated with more than a twofold higher risk of liver cancer (OR: 2.38; 95% CI: 1.06, 5.36) and seropositivity to the H . hepaticus antigens HH0407 or HH1201, or H. bilis antigen, HRAG 01470 were associated with higher risk of biliary cancer (OR: 5.01; 95% CI: 1.53, 16.40; OR: 2.40; 95% CI: 1.00, 5.76; OR: 3.27; 95% CI: 1.14, 9.34, respectively) within PLCO. No associations for any of the H . hepaticus or H . bilis antigens were noted for liver or biliary cancers within ATBC. Conclusions Further investigations in cohort studies should examine the role of Helicobacter spp. in the etiology of liver and biliary cancers.

Gwen Murphy

Neal D. Freedman

Christian C. Abnet

Demetrius Albanes

Amanda J. Cross

Wen‐Yi Huang

Jill Koshiol

Katherine McGlynn

Dominick Parisi

Satu Männistö

Stephanie J. Weinstein

Tim Waterboer

Julia Butt

Helicobacter hepaticus and Helicobacter bilis in liver and biliary cancers from ATBC and PLCO

肝螺杆菌和胆螺杆菌在ATBC和PLCO肝胆癌中的研究

Abstract Background The World Health Organization has identified Helicobacter pylori , a Gram‐negative bacterium responsible for several gastric disorders, as one of the pathogenic bacteria that requires newer non‐antibiotic approaches for its management. We previously demonstrated that nanostructured lipid carriers (NLC) loaded with docosahexaenoic acid (DHA‐NLC) have excellent in vitro performance against H. pylori . Materials and Methods NLC were tested against different H. pylori strains and bacteria representative from human gut microbiota. For H. pylori , resistance development and membrane permeability assays were also performed. In vivo efficacy studies were done using an H. pylori ‐infected mouse model. Microbiome analysis (16S rRNA sequencing analysis) was performed on mice feces before and after DHA‐NLC treatment. Results NLC specifically killed different H. pylori strains by membrane disruption without inducing bacterial resistance. In vivo studies demonstrated that DHA‐NLC (2 mg/mL containing 50 μM of DHA) reduced 90%–95% of the H. pylori burden and eradicated infection in 50% of the animals when treatment was administrated ad libitum for 14 days. No significant differences were found between the administration procedure (ad libitum vs oral gavage). Also, increasing the DHA‐NLC concentration to 4 and 8 mg/mL did not translate into an improvement in antibacterial performance. Notably, gut microbiome analysis showed no alterations, highlighting the safety to the gut microbiota. Finally, no histopathological changes were reported (stomach/liver sections). Conclusions Overall, our results emphasize DHA‐NLC as a promising approach for H. pylori infection management, since they can effectively reduce the H. pylori burden without affecting gut microbiota and, in opposition to antibiotics, without anticipating the development of resistance to this treatment.

Catarina Leal Seabra

A. Sofia Pinho

Cláudia Nunes

Irina Amorim

Nicole Pedro

Patrícia Henriques

Cláudia Monteiro

Joana Gomes

Cláudia Machado

Fátima Gartner

Luísa Pereira

Salette Reis

Celso A. Reis

Eliette Touati

Inês C. Gonçalves

Paula Parreira

M. Cristina L. Martins

Paving the way for a non‐antibiotic and microbiota friendly therapy for Helicobacter pylori: In vitro and in vivo performance of lipid nanoparticles

为非抗生素和微生物群友好型幽门螺杆菌疗法铺平道路：脂质纳米粒的体外和体内性能

HELICOBACTER 由 DAVID Y GRAHAM 教授编辑。编辑和同行评审过程是一个独立的过程。每当有利益冲突时，编辑和编辑委员会都会声明他们的利益和隶属关系。幽门螺杆菌认识到幽门螺杆菌在消化性溃疡、胃腺癌和原发性胃淋巴瘤中的关键作用。由于现在经常发现新的螺杆菌物种，螺杆菌涵盖了螺杆菌研究的整个范围，增加了胃肠病学领域之间的交流；微生物学;疫苗开发；实验动物科学。

The journal "Helicobacter" is edited by Professor David Y. Graham, and the editorial and peer review processes are conducted independently. Whenever there is a conflict of interest, the editors and editorial board declare their interests and affiliations. This journal recognizes the critical role of Helicobacter pylori in peptic ulcers, gastric adenocarcinoma, and primary gastric lymphoma. As new species of Helicobacter are frequently discovered, the journal covers the entire spectrum of Helicobacter research, enhancing communication between the fields of gastroenterology, microbiology, vaccine development, and experimental animal science.

《Helicobacter》期刊由大卫·Y·格雷厄姆教授主编，编辑和同行评审过程是独立进行的。每当出现利益冲突时，编辑和编辑委员会会公开声明他们的利益和隶属关系。该期刊专注于幽门螺杆菌在消化性溃疡、胃腺癌和原发性胃淋巴瘤中的重要作用。随着新螺杆菌物种的不断发现，期刊涵盖了螺杆菌研究的各个领域，促进了胃肠病学、微生物学、疫苗开发和实验动物科学之间的交流。

期刊	Helicobacter
ISSN	1083-4389, 1523-5378
h-index	90
Journal Impact	4.31
国际分区	MICROBIOLOGY(Q2)
国内分区	医学(2区)医学微生物学(2区)医学胃肠肝病学(3区)

Helicobacter

Influence of <scp><i>oipA</i></scp> Phase Variation on Virulence Phenotypes Related to Type <scp>IV</scp> Secretion System in <i>Helicobacter pylori</i>

Optimal Duration of Bismuth‐Containing Quadruple Therapy for <i>Helicobacter pylori</i> Eradication: A Systematic Review and Meta‐Analysis

Efficacy of Tegoprazan‐Containing Sequential Eradication Treatment Compared to Esomeprazole‐Containing Sequential Eradication of <i>Helicobacter pylori</i> in South Korea, a Region With High Antimicrobial Resistance: A Prospective, Randomized, Single Tertiary Center Study

Systematic Review and Meta‐Analysis: Bismuth Enhances the Efficacy for Eradication of <i>Helicobacter pylori</i>

Efficacy of Bismuth Therapy in Eradicating <i>Helicobacter pylori</i> in Children—Data From the <scp>RENIHp</scp> Registry

Glycosyltransferase Jhp0106 (PseE) contributes to flagellin maturation in <i>Helicobacter</i><i>pylori</i>

Concentration‐dependent effect of amoxicillin against clinical strains of <i>Helicobacter pylori</i>

Seroprevalence of <i>Helicobacter pylori</i> infection among schoolchildren in southern Taiwan—A 20‐year longitudinal follow‐up

<i>Helicobacter hepaticus</i> and <i>Helicobacter bilis</i> in liver and biliary cancers from ATBC and PLCO

Paving the way for a non‐antibiotic and microbiota friendly therapy for <i>Helicobacter pylori</i>: In vitro and in vivo performance of lipid nanoparticles