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Development and Evaluation of a Multi-Epitope Vaccine Based on P22 Virus-Like Particles Targeting Helicobacter pylori. 基于P22病毒样颗粒靶向幽门螺杆菌的多表位疫苗的研制与评价
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-07-01 DOI: 10.1111/hel.70058
Yalan Zhu, Jiaxue Yang, Chubin Fang, Chuan Wang, Tian Tang

Background: The current first-line treatment for Helicobacter pylori (H. pylori) infection is bismuth-based quadruple therapy. However, the widespread use of antibiotics has contributed to the emergence of antibiotic-resistant strains, thereby increasing the likelihood of treatment failure. This study aimed to develop a multi-epitope H. pylori vaccine, designated P22-C3, based on P22 Virus-like Particles, with the objective of reducing infection rates and preventing transmission.

Materials and methods: The structural characteristics of P22-C3 were analyzed using transmission electron microscopy (TEM) and dynamic light scattering (DLS). The safety profile of P22-C3 was evaluated through a series of in vitro and in vivo assays. In vitro assessments included cytotoxicity and proinflammatory factor testing. In vivo evaluations, conducted in immunized mice, involved monitoring changes in body weight, biochemical marker fluctuations, and histopathological examinations. The antibody response and T cell-mediated immunity elicited by P22-C3 were quantified using enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. Immune protection efficacy was assessed through a challenge experiment.

Results: P22-C3 successfully self-assembled into T = 7 icosahedral structures with an average diameter of 58 nm. Both in vitro and in vivo experiments confirmed that P22-C3 was safe and well-tolerated. Furthermore, P22-C3 elicited a dose-dependent IgG response and a mixed Th1/Th17 immune profile. In challenge experiments, mice immunized with P22-C3 demonstrated reduced bacterial loads and urease levels in the stomach.

Conclusion: P22-C3 was well-tolerated and successfully induced a strong immune response, offering protection against H. pylori infection. These properties make P22-C3 a promising H. pylori vaccine. It is important to note that this study was conducted solely in mice and did not involve human participants; therefore, a clinical trial registration number is not applicable.

背景:目前治疗幽门螺杆菌(h.p ylori)感染的一线治疗是以铋为基础的四联疗法。然而,抗生素的广泛使用导致了抗生素耐药菌株的出现,从而增加了治疗失败的可能性。本研究旨在以P22病毒样颗粒为基础,开发一种多表位幽门螺杆菌疫苗,命名为P22- c3,以降低感染率和预防传播。材料与方法:采用透射电镜(TEM)和动态光散射(DLS)分析了P22-C3的结构特征。P22-C3的安全性通过一系列体外和体内试验进行评估。体外评估包括细胞毒性和促炎因子测试。在免疫小鼠中进行的体内评估包括监测体重变化、生化指标波动和组织病理学检查。采用酶联免疫吸附法(ELISA)和流式细胞术分别对P22-C3诱导的抗体应答和T细胞介导免疫进行定量分析。通过攻毒实验评价其免疫保护效果。结果:P22-C3成功自组装成T = 7个平均直径为58 nm的二十面体结构。体外和体内实验均证实P22-C3是安全且耐受性良好的。此外,P22-C3引发了剂量依赖性的IgG反应和混合的Th1/Th17免疫谱。在刺激实验中,用P22-C3免疫的小鼠显示出胃中细菌负荷和脲酶水平的降低。结论:P22-C3具有良好的耐受性,可诱导较强的免疫应答,对幽门螺杆菌感染具有保护作用。这些特性使P22-C3成为一种很有前途的幽门螺杆菌疫苗。值得注意的是,这项研究仅在小鼠中进行,没有涉及人类参与者;因此,临床试验注册号不适用。
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引用次数: 0
Helicobacter pylori Eradication in Older Individuals: A Systematic Review and Meta-Analysis. 老年人幽门螺杆菌根除:系统回顾和荟萃分析。
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-07-01 DOI: 10.1111/hel.70059
Sun Jae Moon, Ah Young Lee, Jinseub Hwang, Jun-Young Seo

Background: To determine the clinical effects, efficacy, adverse events, tolerance, and antibiotic resistance of Helicobacter pylori (H. pylori) eradication therapy in the elderly.

Materials and methods: We searched Medline, Embase, CINAHL, Cochrane Library, clinical trial registry, conference proceedings portal, and citation screening. We selected randomized controlled trials (RCTs) or cohort designs including participants aged 60 years or older and reported their clinical effects or efficacy as quantitative indices. Meta-analyses were performed using a random effects model.

Results: A total of 5172 studies were identified, of which 64 were selected for review. The pooled eradication rate of the 10-day sequential therapy was 91% (95% confidence interval [CI], 86%-93%) and that of the 7-day standard triple therapy was 81% (95% CI, 77%-85%). In addition, 7-day levofloxacin-based TT, 14-day hybrid, 14-day bismuth-based QT, 7-day vonoprazan-based TT, and 14-day TT-PAC regimen in RCTs, and non-bismuth-based QT and susceptibility-based therapy in cohort studies showed eradication rates ≥ 95%. The most prevalent gastrointestinal adverse event varied by regimens, with compliance ranging from 87% to 100%. When populations with a history of eradication were included, antibiotic resistance rates exceeded the national prevalence. Three cohorts (the United States, South Korea, and China) reported a protective effect against gastric cancer, although this varied by index and age subgroup.

Conclusions: In the eradication therapy of H. pylori in individuals aged 60 years or older, the 7-day standard triple therapy was unacceptable, and the 10-day sequential therapy was borderline acceptable. The eradication history should be assessed as it may contribute to antibiotic resistance. Although positive reports have emerged regarding the protective effects of gastric cancer on that population, country-specific and conditional recommendations are necessary. Future researchers should report more rigorously on adverse events, tolerance, and antibiotic resistance.

Protocol registration: CRD42024617327.

背景:了解老年人幽门螺杆菌根除治疗的临床效果、疗效、不良事件、耐受性和抗生素耐药性。材料和方法:检索Medline、Embase、CINAHL、Cochrane Library、临床试验注册、会议记录门户和引文筛选。我们选择随机对照试验(RCTs)或队列设计,包括60岁或以上的参与者,并报告其临床效果或疗效作为定量指标。采用随机效应模型进行meta分析。结果:共纳入5172项研究,其中64项纳入综述。10天序贯治疗的总根除率为91%(95%可信区间[CI], 86%-93%), 7天标准三联治疗的总根除率为81% (95% CI, 77%-85%)。此外,在随机对照试验中,以左旋氟沙星为基础的7天TT、14天混合TT、14天铋为基础的QT、7天伏诺哌嗪为基础的TT和14天TT- pac方案,以及在队列研究中以非铋为基础的QT和基于敏感性的治疗,根除率均≥95%。最常见的胃肠道不良事件因治疗方案而异,依从性从87%到100%不等。当包括有根除史的人群时,抗生素耐药率超过了全国流行率。三个队列(美国、韩国和中国)报告了对胃癌的保护作用,尽管这因指数和年龄亚组而异。结论:在60岁及以上人群幽门螺杆菌根除治疗中,7天标准三联治疗是不可接受的,10天序贯治疗是可以接受的。应评估根除历史,因为它可能有助于抗生素耐药性。虽然已经出现了关于胃癌对该人群的保护作用的积极报告,但有必要针对具体国家和有条件的建议。未来的研究人员应该更严格地报告不良事件、耐受性和抗生素耐药性。协议注册:CRD42024617327。
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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—Authors' Reply 致编辑的信:补充乳酸杆菌根除幽门螺杆菌的功效:随机对照试验的系统荟萃分析和试验序列分析-作者回复
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-06-23 DOI: 10.1111/hel.70054
Vivek Mishra, Debabrata Dash, Aditya K. Panda, Sushil Kumar Pathak
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引用次数: 0
The Increasing Trend of the Generational Helicobacter pylori-Naïve Prevalence Among Japanese Individuals Born Between 1925 and 2015: A Systematic Review and Meta-Regression Analysis 日本1925 - 2015年出生人群幽门螺杆菌pylori-Naïve患病率上升趋势:系统回顾与meta回归分析
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-06-11 DOI: 10.1111/hel.70052
Fumiaki Ishibashi, Chikamasa Ichita, Ayaka Takasu, Ran Li, Yasuhiro Hagiwara, Yutaka Matsuyama, Yuichiro Kemmoto, Chika Kusano, Manami Inoue, Nobutake Yamamichi, Hideki Ishikawa, Takuji Gotoda

Background

The World Health Organization has confirmed that Helicobacter pylori is a carcinogen associated with gastric cancer (GC). Although a recent increasing trend in the prevalence of the H. pylori-naïve status has been reported, the precise values of each generation have not yet been specified. This study aimed to confirm the generational H. pylori-naïve prevalence in Japan.

Materials and Methods

Scientific articles available in PubMed and EMBASE between January 2014 and June 2024 were systematically searched. Publications that specified the generational H. pylori-naïve prevalence were included in the analysis. Publications that did not describe the prevalence of H. pylori-naïve individuals and the definition of H. pylori-eradicated individuals were excluded. A meta-regression analysis with a logistic mixed effect model was conducted to predict the generational prevalence of the H. pylori-naïve status. In this model, birth year was incorporated as a spline function to model non-linear trends, and study differences were included as random effects.

Results

A total of 899 publications were identified. After screening, eight publications were included in the final analysis. Nine different study groups comprising 46,704 individuals included in those publications were identified and analyzed. The calculated H. pylori-naïve prevalence rates among the average cohort were 21.1% for births in 1930, 47.2% for births in 1950, 75.3% for births in 1970, 91.7% for births in 1990, and 97.7% for births in 2010.

Conclusions

The H. pylori-naïve prevalence increased dramatically with more recent birth years and reached a plateau of over 95%, especially after 2000. The current GC screening strategy can be modified based on this finding.

背景世界卫生组织已经证实幽门螺杆菌是一种与胃癌相关的致癌物。虽然最近有报道称H. pylori-naïve状态的流行率呈上升趋势,但每一代的精确值尚未明确。本研究旨在确认H. pylori-naïve在日本的代际患病率。材料与方法系统检索2014年1月至2024年6月在PubMed和EMBASE中发表的科学论文。指定世代H. pylori-naïve患病率的出版物包括在分析中。未描述幽门螺杆菌pylori-naïve个体患病率和幽门螺杆菌根除个体定义的出版物被排除在外。采用logistic混合效应模型进行meta回归分析,预测H. pylori-naïve状态的代际患病率。在该模型中,出生年份作为样条函数来模拟非线性趋势,研究差异作为随机效应。结果共鉴定出899篇文献。经过筛选,8份出版物被纳入最终分析。确定并分析了这些出版物中包含的9个不同的研究组,共46,704人。计算的H. pylori-naïve在平均队列中的患病率为:1930年出生21.1%,1950年出生47.2%,1970年出生75.3%,1990年出生91.7%,2010年出生97.7%。结论随着出生年龄的增加,H. pylori-naïve患病率急剧上升,并在2000年以后达到95%以上的平稳期。当前的GC筛选策略可以根据这一发现进行修改。
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引用次数: 0
Efficacy of Three Amoxicillin Doses in Vonoprazan Dual Therapy for Helicobacter pylori Eradication: A Randomized Noninferiority Trial 三种阿莫西林剂量在伏诺帕赞双重治疗中根除幽门螺杆菌的疗效:一项随机非劣效性试验
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-06-07 DOI: 10.1111/hel.70050
Ruolin Peng, Pengpeng Cai, Zhimei Zhang, Shengxiang Lv, Guangxia Chen, Yuling Xu, Bin He, Min Sun, Xiaorong Dai, Kunfeng Yan, Lu Shen, Jianrong Wang, Wei Li, Rui Yin, Jianxin Ge, Duanmin Hu, Kewei Hu, Xiaodan Xu, Hui Li, Chengyu Pan, Zhaotao Duan, Xuefeng Gao, Zhenyu Zhang, Wanli Liu

Background

Limited research has explored the efficacy of reduced amoxicillin dosages in vonoprazan-amoxicillin (VA) dual therapy for Helicobacter pylori eradication in China, and this study aimed to assess the noninferiority of these lower dosages compared to the standard high dose (3 g/d).

Methods

This was a noninferiority study with a −10% margin. H. pylori-positive patients from 13 centers in Jiangsu Province, China, were randomly assigned in a 1:1:1 ratio to receive a 14-day treatment, consisting of vonoprazan (20 mg BID) and high-dose amoxicillin (1 g TID, HVA), medium-dose amoxicillin (1 g BID, MVA), or low-dose amoxicillin (0.5 g TID, LVA). The eradication rates, adverse events (AEs), and medication adherence were compared.

Results

From January 13, 2023 to July 6, 2024, a total of 900 patients were enrolled. According to the intention-to-treat (ITT) and per-protocol (PP) analyses, the eradication rates for HVA, MVA, and LVA groups were 93.2% and 93.2%, 91.6% and 91.5%, and 87.0% and 86.8%, respectively. The efficacy of MVA was noninferior to HVA in ITT analysis (difference: −1.6%, 97.5% CI: −7.0% to 3.8%, p < 0.001) and PP analysis (difference: −1.7%, 97.5% CI: −7.1% to 3.7%, p < 0.001); LVA's effectiveness was less than HVA in ITT analysis (difference: −6.2%, 97.5% CI: −12.2% to −0.2%, p = 0.076) and PP analysis (difference:-6.4%, 97.5% CI: −12.4% to −0.3%, p = 0.089). The incidence of AEs and medication compliance among the three groups was similar.

Conclusions

A 14-day VA regimen requires ≥ 2 g/d amoxicillin to maintain noninferior eradication efficacy versus 3 g/d, supporting dose reduction without compromising effectiveness.

Trial Registration

ClinicalTrials.gov identifier: NCT05649540

背景有限的研究已经探索了减少阿莫西林剂量在vonoprazan-amoxicillin (VA)双重治疗中根除幽门螺杆菌的疗效,本研究旨在评估这些低剂量与标准高剂量(3g /d)相比的非效性。方法:这是一项非劣效性研究,边际为- 10%。来自中国江苏省13个中心的幽门螺旋杆菌阳性患者按1:1:1的比例随机分配,接受为期14天的治疗,包括vonoprazan (20mg BID)和高剂量阿莫西林(1g TID, HVA)、中剂量阿莫西林(1g BID, MVA)或低剂量阿莫西林(0.5 g TID, LVA)。比较根除率、不良事件(ae)和药物依从性。结果2023年1月13日至2024年7月6日,共入组900例患者。根据意向治疗(ITT)和方案分析(PP), HVA、MVA和LVA组的根除率分别为93.2%和93.2%,91.6%和91.5%,87.0%和86.8%。在ITT分析(差异:- 1.6%,97.5% CI: - 7.0%至3.8%,p < 0.001)和PP分析(差异:- 1.7%,97.5% CI: - 7.1%至3.7%,p < 0.001)中,MVA的疗效不逊于HVA;ITT分析中LVA的有效性低于HVA(差异:- 6.2%,97.5% CI: - 12.2%至- 0.2%,p = 0.076)和PP分析中LVA的有效性低于HVA(差异:-6.4%,97.5% CI: - 12.4%至- 0.3%,p = 0.089)。三组患者不良事件发生率及用药依从性相似。结论:14天的VA治疗方案需要≥2g /d的阿莫西林来维持非亚差的根除效果,而不是3g /d,支持在不影响效果的情况下减少剂量。临床试验注册。gov标识符:NCT05649540
{"title":"Efficacy of Three Amoxicillin Doses in Vonoprazan Dual Therapy for Helicobacter pylori Eradication: A Randomized Noninferiority Trial","authors":"Ruolin Peng,&nbsp;Pengpeng Cai,&nbsp;Zhimei Zhang,&nbsp;Shengxiang Lv,&nbsp;Guangxia Chen,&nbsp;Yuling Xu,&nbsp;Bin He,&nbsp;Min Sun,&nbsp;Xiaorong Dai,&nbsp;Kunfeng Yan,&nbsp;Lu Shen,&nbsp;Jianrong Wang,&nbsp;Wei Li,&nbsp;Rui Yin,&nbsp;Jianxin Ge,&nbsp;Duanmin Hu,&nbsp;Kewei Hu,&nbsp;Xiaodan Xu,&nbsp;Hui Li,&nbsp;Chengyu Pan,&nbsp;Zhaotao Duan,&nbsp;Xuefeng Gao,&nbsp;Zhenyu Zhang,&nbsp;Wanli Liu","doi":"10.1111/hel.70050","DOIUrl":"https://doi.org/10.1111/hel.70050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Limited research has explored the efficacy of reduced amoxicillin dosages in vonoprazan-amoxicillin (VA) dual therapy for <i>Helicobacter pylori</i> eradication in China, and this study aimed to assess the noninferiority of these lower dosages compared to the standard high dose (3 g/d).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a noninferiority study with a −10% margin. <i>H. pylori</i>-positive patients from 13 centers in Jiangsu Province, China, were randomly assigned in a 1:1:1 ratio to receive a 14-day treatment, consisting of vonoprazan (20 mg BID) and high-dose amoxicillin (1 g TID, HVA), medium-dose amoxicillin (1 g BID, MVA), or low-dose amoxicillin (0.5 g TID, LVA). The eradication rates, adverse events (AEs), and medication adherence were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From January 13, 2023 to July 6, 2024, a total of 900 patients were enrolled. According to the intention-to-treat (ITT) and per-protocol (PP) analyses, the eradication rates for HVA, MVA, and LVA groups were 93.2% and 93.2%, 91.6% and 91.5%, and 87.0% and 86.8%, respectively. The efficacy of MVA was noninferior to HVA in ITT analysis (difference: −1.6%, 97.5% CI: −7.0% to 3.8%, <i>p</i> &lt; 0.001) and PP analysis (difference: −1.7%, 97.5% CI: −7.1% to 3.7%, <i>p</i> &lt; 0.001); LVA's effectiveness was less than HVA in ITT analysis (difference: −6.2%, 97.5% CI: −12.2% to −0.2%, <i>p</i> = 0.076) and PP analysis (difference:-6.4%, 97.5% CI: −12.4% to −0.3%, <i>p</i> = 0.089). The incidence of AEs and medication compliance among the three groups was similar.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A 14-day VA regimen requires ≥ 2 g/d amoxicillin to maintain noninferior eradication efficacy versus 3 g/d, supporting dose reduction without compromising effectiveness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifier: NCT05649540</p>\u0000 </section>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144232465","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
Authors' Reply to the Letter on “Is Tailored Bismuth Quadruple Therapy (With Clarithromycin or Furazolidone) Based on Fecal Molecular Susceptibility Testing in First-Line Helicobacter pylori Eradication Treatment More Effective? A Three-Arm, Multicenter Randomized Clinical Trial” 作者对“基于粪便分子药敏试验的定制铋四联疗法(克拉霉素或呋喃唑酮)在一线幽门螺杆菌根除治疗中更有效吗?”一项三组、多中心随机临床试验
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-06-05 DOI: 10.1111/hel.70049
Zhengchen Yu, Wenjuan Shen, Guochun Lou, Yan Li, Ziming Xie, Jun Ye

We appreciate the valuable comments and thoughtful critique offered by the reader regarding our study on tailored bismuth quadruple therapy based on fecal molecular susceptibility testing in first-line Helicobacter pylori eradication. In our response, we have sought to clarify the methodological rationale underlying our statistical analysis and terminology usage, particularly regarding superiority and non-inferiority testing. We have also addressed concerns regarding assessing prior macrolide exposure, outlining the practical considerations that informed our study design. We trust that our clarifications will help to elucidate the study's context and findings further, and we welcome continued academic dialogue on this important topic.

我们感谢读者对我们基于粪便分子药敏试验的量身定制的铋四联疗法在一线根除幽门螺杆菌的研究提供的宝贵意见和周到的批评。在我们的回应中,我们试图澄清我们的统计分析和术语使用的方法学原理,特别是关于优势和非劣效性检验。我们还讨论了评估先前大环内酯暴露的问题,概述了我们研究设计的实际考虑因素。我们相信,我们的澄清将有助于进一步阐明这项研究的背景和结果,我们欢迎就这一重要主题继续进行学术对话。
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引用次数: 0
Roles of Gastric Non-Helicobacter pylori Helicobacter Species in Gastric Disease Development: A Review 胃非幽门螺杆菌幽门螺杆菌在胃病发展中的作用综述
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-06-03 DOI: 10.1111/hel.70051
Mitsushige Sugimoto, Emiko Rimbara, Masaki Murata, Yoshio Yamaoka

Gastric Helicobacter species, including Helicobacter pylori and non-Helicobacter pylori Helicobacter (NHPH) species, are gram-negative fastidious bacteria that colonize the stomachs of both humans and animals such as pigs, dogs, cats, and monkeys. The H. pylori infection rate is decreasing due to improved living conditions and increased opportunities for H. pylori eradication therapy in developed countries. However, concerns about NHPH infection-induced gastric diseases are growing, especially low-grade gastric mucosa-associated lymphoid tissue lymphoma. Although NHPH infections have been reported for 30 years, especially H. suis infections, evidence of the correct infection rate, route of infection to humans, and direct and indirect associations with gastric diseases are insufficient. Presently, NHPH infection can be diagnosed using histopathological and immunohistochemical findings, polymerase chain reaction, culture tests, or enzyme-linked immunosorbent assays. Several basic and clinical studies have begun to report the bacteriologic characteristics and routes of NHPH infection. In addition, the high effectiveness of eradication therapy using a combination of an acid inhibitor and two types of antibiotics, which is the same eradication regimen for H. pylori infection, has been reported. However, evidence on antibiotic resistance, appropriate dosing dosage, or drug type provided by randomized control trials is lacking. Several issues regarding the etiology, virulence, diagnosis, and treatment of NHPH infections should be addressed in the future.

胃幽门螺杆菌种类,包括幽门螺杆菌和非幽门螺杆菌(NHPH)种类,是革兰氏阴性挑剔细菌,定植在人类和动物(如猪、狗、猫和猴子)的胃里。由于发达国家生活条件的改善和幽门螺杆菌根除治疗机会的增加,幽门螺杆菌感染率正在下降。然而,对NHPH感染引起的胃疾病的关注越来越多,特别是低级别胃粘膜相关淋巴组织淋巴瘤。尽管NHPH感染已有30年的报道,特别是猪嗜血杆菌感染,但正确的感染率、感染人的途径以及与胃疾病的直接和间接关联的证据不足。目前,NHPH感染可以通过组织病理学和免疫组织化学检查、聚合酶链反应、培养试验或酶联免疫吸附试验来诊断。一些基础和临床研究已经开始报道NHPH感染的细菌学特征和途径。此外,据报道,使用一种酸抑制剂和两种抗生素的联合根除治疗具有很高的效果,这是根除幽门螺杆菌感染的相同方案。然而,缺乏随机对照试验提供的抗生素耐药性、适当剂量或药物类型的证据。关于NHPH感染的病因、毒力、诊断和治疗的几个问题应该在未来得到解决。
{"title":"Roles of Gastric Non-Helicobacter pylori Helicobacter Species in Gastric Disease Development: A Review","authors":"Mitsushige Sugimoto,&nbsp;Emiko Rimbara,&nbsp;Masaki Murata,&nbsp;Yoshio Yamaoka","doi":"10.1111/hel.70051","DOIUrl":"https://doi.org/10.1111/hel.70051","url":null,"abstract":"<div>\u0000 \u0000 <p>Gastric <i>Helicobacter</i> species, including <i>Helicobacter pylori</i> and non-<i>Helicobacter pylori Helicobacter</i> (NHPH) species, are gram-negative fastidious bacteria that colonize the stomachs of both humans and animals such as pigs, dogs, cats, and monkeys. The <i>H. pylori</i> infection rate is decreasing due to improved living conditions and increased opportunities for <i>H. pylori</i> eradication therapy in developed countries. However, concerns about NHPH infection-induced gastric diseases are growing, especially low-grade gastric mucosa-associated lymphoid tissue lymphoma. Although NHPH infections have been reported for 30 years, especially <i>H. suis</i> infections, evidence of the correct infection rate, route of infection to humans, and direct and indirect associations with gastric diseases are insufficient. Presently, NHPH infection can be diagnosed using histopathological and immunohistochemical findings, polymerase chain reaction, culture tests, or enzyme-linked immunosorbent assays. Several basic and clinical studies have begun to report the bacteriologic characteristics and routes of NHPH infection. In addition, the high effectiveness of eradication therapy using a combination of an acid inhibitor and two types of antibiotics, which is the same eradication regimen for <i>H. pylori</i> infection, has been reported. However, evidence on antibiotic resistance, appropriate dosing dosage, or drug type provided by randomized control trials is lacking. Several issues regarding the etiology, virulence, diagnosis, and treatment of NHPH infections should be addressed in the future.</p>\u0000 </div>","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144206735","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
Letter to the Editor: “Parietal Cell Antibody Levels Among Chronic Gastritis Patients in a Country With Low Helicobacter pylori Infection: Epidemiology, Histopathological Features, and H. pylori Infection” 致编辑的信:“幽门螺杆菌低感染率国家慢性胃炎患者的壁细胞抗体水平:流行病学、组织病理学特征和幽门螺杆菌感染”
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-06-03 DOI: 10.1111/hel.70053
Xiaopei Guo, Manon C W Spaander, Gwenny M Fuhler
<p>We read with great interest the article titled “Parietal Cell Antibody Levels Among Chronic Gastritis Patients in a Country with Low <i>Helicobacter pylori</i> Infection: Epidemiology, Histopathological Features, and <i>H. pylori</i> infection” by Amalia et al. [<span>1</span>]. In this study, the authors investigated the prevalence of autoimmune gastritis (AIG), and its association with <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection status and gastric histopathological features in the Indonesian population. Given the previously reported high incidence of gastritis and relatively low <i>H. pylori</i> infection rates in this region, exploring other causes of gastritis, such as AIG, is essential for improving diagnostic accuracy and guiding clinical risk management [<span>2</span>].</p><p>While the authors conducted a comprehensive analysis of parietal cell antibody (PCA) levels and its association with clinicopathological features, several aspects of the study's methodology and interpretation raise concerns and warrant further clarification. A key observation of this study is the reported 78.99% prevalence of PCA positivity among 113 Indonesian patients with chronic gastritis and 25 healthy controls, while only one patient was diagnosed with AIG. The authors suggest that this discrepancy might be due to <i>H. pylori</i>-associated immune activation. However, we think it may also reflect the combined impact of overly strict diagnostic criteria for AIG and the inappropriate interpretation of PCA results.</p><p>In the diagnostic methods, AIG was defined based on the PCA positivity, absence of <i>H. pylori</i> infection, histopathological features associated with AIG, and sparing of the antrum. We understand the concern that coexisting <i>H. pylori</i> infection may complicate the diagnosis of AIG, as it can cause histopathological changes that resemble AIG. But we note that neither antrum sparing nor negative <i>H. pylori</i>-negative status should be a required criterion for AIG diagnosis. Our previous findings have shown that AIG can coexist with <i>H. pylori</i> infection, and hence patients may present with antral inflammation or atrophy. Such patients still show characteristic serological features similar to AIG patients without <i>H. pylori</i> infection, including decreased pepsinogen (PG) I levels and elevated gastrin 17 [<span>3</span>]. Additionally, they may exhibit pathological findings such as enterochromaffin-like (ECL) cell hyperplasia [<span>4</span>], which was not investigated in the study by Amalia et al. Therefore, we think the criteria used may have led to underdiagnosis of AIG in the Indonesia cohort. Rather than excluding patients with <i>H. pylori</i> infection or antrum inflammation/atrophy, more specific diagnostic tests should be considered to improve the diagnosis of AIG, especially given this is the first study reporting AIG prevalence in this region.</p><p>Adding to these diagnostic challenges Beyond these di
我们饶有兴趣地阅读了Amalia等人的文章《幽门螺杆菌低感染率国家慢性胃炎患者的壁细胞抗体水平:流行病学、组织病理学特征和幽门螺杆菌感染》[b]。在这项研究中,作者调查了印尼人群中自身免疫性胃炎(AIG)的患病率及其与幽门螺杆菌(h.p ylori)感染状况和胃组织病理学特征的关系。鉴于先前报道的该地区胃炎发病率高,幽门螺杆菌感染率相对较低,探索其他胃炎原因,如AIG,对于提高诊断准确性和指导临床风险管理bbb至关重要。虽然作者对壁细胞抗体(PCA)水平及其与临床病理特征的关系进行了全面分析,但该研究方法和解释的几个方面引起了关注,需要进一步澄清。本研究的一个关键观察结果是,在113名印度尼西亚慢性胃炎患者和25名健康对照者中,PCA阳性率为78.99%,而只有1名患者被诊断为AIG。作者认为这种差异可能是由于幽门螺杆菌相关的免疫激活。然而,我们认为这也可能反映了AIG过于严格的诊断标准和对PCA结果的不适当解释的综合影响。在诊断方法中,AIG的定义是基于PCA阳性,没有幽门螺杆菌感染,AIG相关的组织病理学特征,以及保留上腔。我们了解并发幽门螺杆菌感染可能使AIG的诊断复杂化的担忧,因为它可以引起类似AIG的组织病理学改变。但我们注意到,无论是胃窦保留还是幽门螺杆菌阴性状态都不应作为AIG诊断的必要标准。我们之前的研究结果表明,AIG可以与幽门螺杆菌感染共存,因此患者可能出现胃窦炎症或萎缩。这类患者仍表现出与未感染幽门螺杆菌的AIG患者相似的血清学特征,包括胃蛋白酶原(PG) I水平降低和胃泌素水平升高。此外,它们还可能表现出肠色素样(ECL)细胞增生[4]等病理表现,Amalia等人并未对此进行研究。因此,我们认为所使用的标准可能导致印度尼西亚队列中AIG的诊断不足。而不是排除幽门螺杆菌感染或上腔炎症/萎缩的患者,更具体的诊断测试应考虑提高AIG的诊断,特别是考虑到这是第一个研究报告AIG在该地区的流行。除了这些诊断标准之外,本研究中用于检测PCA的方法也需要仔细考虑。Amalia等人使用间接免疫荧光抗体试验(IFT)检测PCA的存在,这是一种半定量方法,灵敏度高,但特异性有限。值得注意的是,近一半的患者具有临界PCA水平(10单位/mL,在检测范围从0到300单位/mL,其中10单位/mL是第一个离散值),这需要仔细解释。我们自己的研究表明,256例患者中有81例(31.6%)使用IFT检测为PCA阳性,但只有18%的患者通过H+/K+- atp酶特异性EliA(一种自动定量酶荧光免疫测定法)和病理bbb证实为阳性。此外,研究表明,在一般健康成人人群中,PCA的发生率较低,他们可能永远不会发生AIG或恶性贫血[3,5]。虽然Amalia等人显示了胃体炎症评分与PCA水平之间的相关性,但从他们的报告中尚不清楚对照组与胃炎患者相比是否表现出较低的PCA患病率。因此,可能需要额外的测试来证明PCA的存在。作者认为,在该队列中观察到的高PCA患病率与幽门螺杆菌感染之间存在潜在联系。虽然幽门螺杆菌可以通过分子模仿引发自身免疫反应的假设在生物学上是合理的,但本研究中提供的当前PCA数据可能在一定程度上限制了这一解释的可信度。为了进一步探讨这一点,我们检查了81例胃萎缩患者的数据,发现有幽门螺杆菌感染和没有幽门螺杆菌感染的患者的PCA水平(由EliA测定)没有显著差异(36.1比39.4,p = 0.24,图1A)。进一步的相关分析显示,在幽门螺杆菌感染患者中,血清PCA水平高度与幽门螺杆菌抗体滴度无关(r = 0.08, p = 0.66,图1B)。最后,作者检查了幽门螺杆菌抗体水平和PCA水平与临床病理特征(如炎症、萎缩和PG I/II比值)的关系。 他们的研究结果表明,幽门螺杆菌抗体和PCA水平在胃窦或身体炎症患者以及萎缩患者中较高。鉴于已知幽门螺杆菌感染和AIG会引起炎症和萎缩性粘膜改变,这似乎是意料之中的。然而,幽门螺杆菌感染患者和AIG患者的抗体滴度高度可能受到患者遗传、BMI、细菌负荷、免疫应答、抗体衰减和许多其他因素的影响。因此,目前尚不清楚IgG水平与萎缩阶段之间的相关性在生物学上意味着什么,并且在将幽门螺杆菌血清阴性和PCA阴性患者从线性回归分析中排除后,观察相关性是否仍然显著将是一件有趣的事情。我们自己的数据显示,至少在我们的胃癌前病变患者队列中,由OLGA评分确定的萎缩水平与抗h抗体IgG水平无关。螺杆菌抗体(r =−0.05,p = 0.70,图1 c)或PCA (r = 0.09, p = 0.69,图1 d)。总之,我们认为Amalia等人使用的诊断标准可能导致低估了印尼队列中AIG的患病率,而高估了PCA的患病率。更具体的血清学检测(如EliA、抗内因子抗体、胃蛋白酶原I和胃泌素-17)和其他组织学特征(如肠嗜铬细胞样(ECL)细胞增生)应结合,以提高PCA的检测和AIG的诊断。郭小培:构思,撰写原稿。Manon C . W . Spaander:概念化、审查和编辑。格温妮·M·富勒:概念化、写作和编辑。作者没有什么可报告的。该研究得到了Erasmus MC医学伦理审查委员会(MEC-2009-090)的批准,并获得了所有参与者的知情同意。
{"title":"Letter to the Editor: “Parietal Cell Antibody Levels Among Chronic Gastritis Patients in a Country With Low Helicobacter pylori Infection: Epidemiology, Histopathological Features, and H. pylori Infection”","authors":"Xiaopei Guo,&nbsp;Manon C W Spaander,&nbsp;Gwenny M Fuhler","doi":"10.1111/hel.70053","DOIUrl":"https://doi.org/10.1111/hel.70053","url":null,"abstract":"&lt;p&gt;We read with great interest the article titled “Parietal Cell Antibody Levels Among Chronic Gastritis Patients in a Country with Low &lt;i&gt;Helicobacter pylori&lt;/i&gt; Infection: Epidemiology, Histopathological Features, and &lt;i&gt;H. pylori&lt;/i&gt; infection” by Amalia et al. [&lt;span&gt;1&lt;/span&gt;]. In this study, the authors investigated the prevalence of autoimmune gastritis (AIG), and its association with &lt;i&gt;Helicobacter pylori&lt;/i&gt; (&lt;i&gt;H. pylori&lt;/i&gt;) infection status and gastric histopathological features in the Indonesian population. Given the previously reported high incidence of gastritis and relatively low &lt;i&gt;H. pylori&lt;/i&gt; infection rates in this region, exploring other causes of gastritis, such as AIG, is essential for improving diagnostic accuracy and guiding clinical risk management [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;While the authors conducted a comprehensive analysis of parietal cell antibody (PCA) levels and its association with clinicopathological features, several aspects of the study's methodology and interpretation raise concerns and warrant further clarification. A key observation of this study is the reported 78.99% prevalence of PCA positivity among 113 Indonesian patients with chronic gastritis and 25 healthy controls, while only one patient was diagnosed with AIG. The authors suggest that this discrepancy might be due to &lt;i&gt;H. pylori&lt;/i&gt;-associated immune activation. However, we think it may also reflect the combined impact of overly strict diagnostic criteria for AIG and the inappropriate interpretation of PCA results.&lt;/p&gt;&lt;p&gt;In the diagnostic methods, AIG was defined based on the PCA positivity, absence of &lt;i&gt;H. pylori&lt;/i&gt; infection, histopathological features associated with AIG, and sparing of the antrum. We understand the concern that coexisting &lt;i&gt;H. pylori&lt;/i&gt; infection may complicate the diagnosis of AIG, as it can cause histopathological changes that resemble AIG. But we note that neither antrum sparing nor negative &lt;i&gt;H. pylori&lt;/i&gt;-negative status should be a required criterion for AIG diagnosis. Our previous findings have shown that AIG can coexist with &lt;i&gt;H. pylori&lt;/i&gt; infection, and hence patients may present with antral inflammation or atrophy. Such patients still show characteristic serological features similar to AIG patients without &lt;i&gt;H. pylori&lt;/i&gt; infection, including decreased pepsinogen (PG) I levels and elevated gastrin 17 [&lt;span&gt;3&lt;/span&gt;]. Additionally, they may exhibit pathological findings such as enterochromaffin-like (ECL) cell hyperplasia [&lt;span&gt;4&lt;/span&gt;], which was not investigated in the study by Amalia et al. Therefore, we think the criteria used may have led to underdiagnosis of AIG in the Indonesia cohort. Rather than excluding patients with &lt;i&gt;H. pylori&lt;/i&gt; infection or antrum inflammation/atrophy, more specific diagnostic tests should be considered to improve the diagnosis of AIG, especially given this is the first study reporting AIG prevalence in this region.&lt;/p&gt;&lt;p&gt;Adding to these diagnostic challenges Beyond these di","PeriodicalId":13223,"journal":{"name":"Helicobacter","volume":"30 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hel.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144206830","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
The Systemic Impact of Helicobacter pylori Infection on the Microbiome of Whole Digestive Tract Based on Mucosal, Gastric Juice, and Fecal Specimens 基于粘膜、胃液和粪便标本的幽门螺杆菌感染对全消化道微生物群的全身影响
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-05-27 DOI: 10.1111/hel.70047
Yuxin Wang, Kai Zhou, Yuexi Zhang, Cailing Li, Yuxin Zhang, Xinlu Ren, Changmin Mi, Lingling Ma, Yuqi Duan, Mengqi Liu, Guangjie Ping, Xueli Tian, Zhiqiang Song
<div> <section> <h3> Background</h3> <p>Recent studies have found that in addition to directly impacting the gastric microbiome, <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection may cause intestinal microbial dysbiosis. However, most existing studies on the influence of <i>H. pylori</i> infection on the intestinal microbiome used fecal specimens with inconsistent conclusions. Only one limited study on 8 <i>H. pylori</i>-infected patients has previously assessed the impact of <i>H. pylori</i> infection on the microbiome of the entire gastrointestinal tract, finding no significant effect on the bacterial composition of the lower gastrointestinal tract.</p> </section> <section> <h3> Methods</h3> <p>This single-center cross-sectional study collected mucosa of the esophagus, stomach, small intestine, and colon, as well as gastric juice and feces from 120 participants of the <i>H. pylori-</i>infected group (HIG) and 30 of the healthy control group (HCG). 16S rRNA sequencing was applied to analyze the bacterial composition and functional pathways, and metagenomics was adopted to assess the composition of viruses, eukaryotes, and archaea in the feces, as well as the antibiotic resistance gene (ARG) and virulence factors of bacteria (VF).</p> </section> <section> <h3> Results</h3> <p>Compared with the HCG, the alpha and beta diversity of bacteria in the mucosa of the whole digestive tract and the gastric juice of the HIG showed significant changes, with increased microbial dysbiosis index and significantly different compositions at the phylum and genus levels. Functional pathway analysis revealed that the metabolic characteristics of the flora changed in the HIG, with site-specific differences. Fecal specimens demonstrated no significant differences in the above indicators between the two groups. In addition, feces-based metagenomic analysis revealed that only eukaryotes had higher diversity in the HIG, whereas viruses and archaea showed no significant changes; the Shannon index of ARG increased; and VF showed no significant change.</p> </section> <section> <h3> Conclusions</h3> <p>This study revealed that <i>H. pylori</i> infection significantly influenced the diversity, composition, and metabolic functional pathway of bacteria in different parts of the digestive tract and the gastric juice. Moreover, fecal microbial composition may not fully represent the mucosal microbial composition of the gastrointestinal tract.</p> </section> <section> <h3> Trial Registration</h3> <p>Chinese Clinical Trial Registry: ChiCTR2300073419</p> </section>
近年研究发现,幽门螺杆菌感染除了直接影响胃微生物群外,还可能引起肠道微生物生态失调。然而,现有关于幽门螺杆菌感染对肠道微生物群影响的研究大多采用粪便标本,结论不一致。先前只有一项针对8名幽门螺杆菌感染患者的有限研究评估了幽门螺杆菌感染对整个胃肠道微生物组的影响,发现对下胃肠道细菌组成没有显著影响。方法采用单中心横断面研究方法,采集120例幽门螺旋杆菌感染组(HIG)和30例健康对照组(HCG)的食管、胃、小肠、结肠粘膜、胃液和粪便。采用16S rRNA测序分析细菌组成和功能途径,采用宏基因组学方法评估粪便中病毒、真核生物和古细菌的组成,以及细菌的抗生素耐药基因(ARG)和毒力因子(VF)。结果与HCG相比,HIG全消化道黏膜和胃液中α和β细菌多样性发生了显著变化,微生物生态失调指数升高,在门和属水平上的组成差异显著。功能通路分析显示,HIG菌群的代谢特征发生了变化,且存在位点特异性差异。两组粪便标本在上述指标上均无显著差异。此外,基于粪便的宏基因组分析显示,HIG中只有真核生物具有更高的多样性,而病毒和古细菌没有明显变化;ARG Shannon指数升高;VF无明显变化。结论幽门螺旋杆菌感染显著影响了消化道和胃液不同部位细菌的多样性、组成和代谢功能途径。此外,粪便微生物组成可能不能完全代表胃肠道的粘膜微生物组成。中国临床试验注册中心:ChiCTR2300073419
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引用次数: 0
Dr Martin Bingham Skirrow—A Passionate Microbiologist and Early Advocate for Helicobacter pylori Martin Bingham skirrow博士是一位充满激情的微生物学家和幽门螺杆菌的早期倡导者
IF 4.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-05-27 DOI: 10.1111/hel.70048
Cliodna McNulty
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引用次数: 0
期刊
Helicobacter
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