Helicobacter最新文献_第8页

Comparison of Helicobacter pylori eradication rates between 7 and 14 days of tailored therapy according to clarithromycin resistance test: A randomized, multicenter, non-inferiority study 根据克拉霉素耐药性测试结果比较 7 天和 14 天定制疗法的幽门螺杆菌根除率：一项随机、多中心、非劣效性研究。

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-05-08 DOI: 10.1111/hel.13084

Kyoungwon Jung, Sam Ryong Jee, Moon Won Lee, Myeongseok Koh, Su Jin Kim, Jin Lee, Moo In Park

Background

Recently, a simple tailored therapy based on clarithromycin resistance has been implemented as Helicobacter pylori (H. pylori) eradication therapy. Nonetheless, despite the tailored therapy and frequent adverse events, studies on treatment period are lacking. This study aimed to compare the H. pylori eradication rates of 7-day and 14-day tailored therapy regimens according to clarithromycin resistance.

Materials and Methods

This multicenter, prospective, randomized, noninferiority trial enrolled H. pylori-positive patients who were randomly assigned to 7-day and 14-day regimen groups, depending on the presence or absence of clarithromycin resistance by 23S rRNA gene point mutations. Standard triple therapy (STT) (20 mg rabeprazole, 1 g amoxicillin, and 500 mg clarithromycin twice daily) or bismuth quadruple therapy (BQT) (20 mg rabeprazole twice daily, 500 mg metronidazole thrice daily, 120 mg bismuth four times daily, and 500 mg tetracycline four times daily) was assigned by clarithromycin resistance. Eradication rates and adverse events were evaluated.

Results

A total of 314 and 278 patients were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively; however, 31 patients were lost to follow-up, whereas five patients violated the protocol. Both the 7-day and 14-day regimens showed similar eradication rates in the ITT (7-day vs. 14-day: 78.3% vs. 78.3%, p > 0.99) and PP (87.9% vs. 89.1%, p = 0.851) analyses. Non-inferiority was confirmed (p < 0.025). A subgroup analysis according to clarithromycin resistance (clarithromycin resistance rate: 28.7%) revealed no significant difference in eradication rates between the 7-day and 14-day STT (90.0% vs. 90.1%, p > 0.99) and BQT (82.5% vs. 86.5%, p = 0.757). Furthermore, adverse events did not significantly differ between the two groups.

Conclusions

The 7-day triple and quadruple therapy according to clarithromycin resistance showed similar eradication rates, as compared to the 14-day therapy.

背景：最近，一种基于克拉霉素耐药性的简单定制疗法已被作为根除幽门螺旋杆菌（H. pylori）的疗法。然而，尽管这种定制疗法不良反应频发，但却缺乏对治疗周期的研究。本研究旨在根据克拉霉素耐药性，比较7天和14天定制治疗方案的幽门螺杆菌根除率：这项多中心、前瞻性、随机、非劣效性试验招募了幽门螺杆菌阳性患者，根据他们是否因 23S rRNA 基因点突变而对克拉霉素产生耐药性，将他们随机分配到 7 天和 14 天治疗方案组。根据克拉霉素耐药性分配标准三联疗法（STT）（20 毫克雷贝拉唑、1 克阿莫西林和 500 毫克克拉霉素，每天两次）或铋剂四联疗法（BQT）（20 毫克雷贝拉唑，每天两次；500 毫克甲硝唑，每天三次；120 毫克铋剂，每天四次；500 毫克四环素，每天四次）。对根除率和不良反应进行了评估：共有314名和278名患者分别被纳入意向治疗（ITT）和按协议（PP）分析；但有31名患者失去了随访机会，另有5名患者违反了协议。在 ITT（7 天与 14 天：78.3% 与 78.3%，p > 0.99）和 PP（87.9% 与 89.1%，p = 0.851）分析中，7 天和 14 天疗法的根除率相似。非劣效性得到证实（p 0.99），BQT（82.5% 对 86.5%，p = 0.757）。此外，两组的不良反应没有明显差异：结论：与 14 天疗法相比，根据克拉霉素耐药性采用的 7 天三联和四联疗法显示出相似的根除率。

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引用次数: 0

Helicobacter pylori with trx1 high expression promotes gastric diseases via upregulating the IL23A/NF-κB/IL8 pathway 高表达 trx1 的幽门螺杆菌通过上调 IL23A/NF-κB/IL8 通路诱发胃病

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-04-30 DOI: 10.1111/hel.13072

Xin Guan, Jing Ning, Weiwei Fu, Ye Wang, Jing Zhang, Shigang Ding

Background

Helicobacter pylori infection is one of the main causes of gastric cancer. thioredoxin-1 (Trx1) and arginase (RocF) expressed by H. pylori were found to be closely related to its pathogenicity. However, whether Trx1 and RocF can be used in clinical screening of highly pathogenic H. pylori and the pathogenesis of trx1 high expressing H. pylori remain still unknown.

Materials and Methods

We investigated the expression level of H. pylori trx1 and H. pylori rocF in human gastric antrum tissues using reverse transcription and quantitative real-time PCR (RT-qPCR) and clarified the clinical application value of trx1 and rocF for screening highly pathogenic H. pylori. The pathogenic mechanism of Trx1 were further explored by RNA-seq of GES-1 cells co-cultured with trx1 high or low expressing H. pylori. Differentially expressed genes and signaling pathways were validated by RT-qPCR, Enzyme-linked immunosorbent assay (ELISA), western blot, immunohistochemistry and immunofluorescence. We also assessed the adherence of trx1 high and low expressing H. pylori to GES-1 cells.

Results

We found that H. pylori trx1 and H. pylori rocF were more significantly expressed in the gastric cancer and peptic ulcer group than that in the gastritis group and the parallel diagnosis of H. pylori trx1 and H. pylori rocF had high sensitivity. The trx1 high expressing H. pylori had stronger adhesion ability to GES-1 cells and upregulated the interleukin (IL) 23A/nuclear factor κappaB (NF-κB)/IL17A, IL6, IL8 pathway.

Conclusions

H. pylori trx1 and H. pylori rocF can be used in clinical screening of highly pathogenic H. pylori and predicting the outcome of H. pylori infection. The trx1 high expressing H. pylori has stronger adhesion capacity and promotes the development of gastric diseases by upregulating the activation of NF-κB signaling pathway.

背景幽门螺杆菌感染是导致胃癌的主要原因之一。研究发现，幽门螺杆菌表达的硫氧还蛋白-1（Trx1）和精氨酸酶（RocF）与其致病性密切相关。然而，Trx1和RocF是否可用于临床筛查高致病性幽门螺杆菌以及高表达Trx1幽门螺杆菌的致病机理仍是未知数。材料与方法我们采用逆转录和实时定量 PCR（RT-qPCR）技术研究了人胃窦组织中幽门螺杆菌 trx1 和幽门螺杆菌 rocF 的表达水平，并明确了 trx1 和 rocF 在筛选高致病性幽门螺杆菌中的临床应用价值。通过对与高表达或低表达 trx1 幽门螺杆菌共培养的 GES-1 细胞进行 RNA 序列分析，进一步探讨了 Trx1 的致病机制。通过 RT-qPCR、酶联免疫吸附试验（ELISA）、Western 印迹、免疫组织化学和免疫荧光验证了不同表达的基因和信号通路。我们还评估了高表达和低表达 trx1 幽门螺杆菌对 GES-1 细胞的粘附性。结果我们发现，幽门螺杆菌 trx1 和幽门螺杆菌 rocF 在胃癌和消化性溃疡组中的表达量明显高于胃炎组，幽门螺杆菌 trx1 和幽门螺杆菌 rocF 的平行诊断灵敏度很高。trx1高表达幽门螺杆菌对GES-1细胞有更强的粘附能力，并上调白细胞介素（IL）23A/核因子κκB（NF-κB）/IL17A、IL6、IL8通路。结论幽门螺杆菌 trx1 和幽门螺杆菌 rocF 可用于临床筛查高致病性幽门螺杆菌和预测幽门螺杆菌感染的结果。高表达的幽门螺杆菌 trx1 具有更强的粘附能力，并通过上调 NF-κB 信号通路的活化促进胃病的发展。

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引用次数: 0

Dynamic changes in the gut microbiota after bismuth quadruple therapy and high-dose dual therapy for Helicobacter pylori eradication 根除幽门螺旋杆菌的四联铋疗法和大剂量双重疗法后肠道微生物群的动态变化

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-04-29 DOI: 10.1111/hel.13077

Jing Chen, Yan Zhang, Hanchen Min, Junli Zhi, Shuyun Ma, Hongxia Dong, Jingshuang Yan, Xiaoyan Chi, Xiaomei Zhang, Yunsheng Yang

Background

A novel regimen with high-dose dual therapy (HDDT) has emerged, but its impact on the gut microbiota is not well understood. This study aimed to evaluate the impact of HDDT on the gut microbiota and compare it with that of bismuth quadruple therapy (BQT).

Methods

We enrolled outpatients (18–70 years) diagnosed with Helicobacter pylori infection by either histology or a positive ¹³C-urea breath test (¹³C-UBT) and randomly assigned to either the BQT or HDDT group. Subjects consented to provide fecal samples which were collected at baseline, Week 2, and Week 14. Amplification of the V1 and V9 regions of the 16S rRNA was conducted followed by high-throughput sequencing.

Results

Ultimately, 78 patients (41 patients in the HDDT group and 37 in the BQT group) were enrolled in this study. Eradication therapy significantly altered the diversity of the gut microbiota. However, the alpha diversity rebounded only in the HDDT group at 12 weeks post-eradication. Immediately following eradication, the predominance of Proteobacteria, replacing commensal Firmicutes and Bacteroidetes, did not recover after 12 weeks. Species-level analysis showed that the relative abundances of Klebsiella pneumoniae and Escherichia fergusonii significantly increased in both groups at Week 2. Enterococcus faecium and Enterococcus faecalis significantly increased in the BQT group, with no significant difference observed in the HDDT group. After 12 weeks of treatment, the relative abundance of more species in the HDDT group returned to baseline levels.

Conclusion

Eradication of H. pylori can lead to an imbalance in gut microbiota. Compared to BQT, the HDDT is a regimen with milder impact on gut microbiota.

背景一种新型的高剂量双重疗法（HDDT）已经出现，但其对肠道微生物群的影响还不甚了解。本研究旨在评估 HDDT 对肠道微生物群的影响，并将其与四联铋剂疗法（BQT）进行比较。方法我们招募了通过组织学检查或 13C-urea 呼气试验（13C-UBT）阳性确诊为幽门螺杆菌感染的门诊患者（18-70 岁），并将其随机分配到 BQT 组或 HDDT 组。受试者同意在基线、第 2 周和第 14 周提供粪便样本。对 16S rRNA 的 V1 和 V9 区域进行扩增，然后进行高通量测序。结果最终，78 名患者（HDDT 组 41 人，BQT 组 37 人）参与了这项研究。根除疗法明显改变了肠道微生物群的多样性。然而，只有 HDDT 组的阿尔法多样性在根除后 12 周内有所恢复。根除后，变形菌立即占据主导地位，取代了共生的固有菌和类杆菌，但在 12 周后并未恢复。物种水平分析表明，在第 2 周时，两组中肺炎克雷伯菌和弗氏埃希氏菌的相对丰度都显著增加。粪肠球菌和粪肠球菌在 BQT 组明显增加，而在 HDDT 组未观察到明显差异。治疗 12 周后，HDDT 组中更多物种的相对丰度恢复到基线水平。结论根除幽门螺杆菌会导致肠道微生物群失衡。与 BQT 相比，HDDT 对肠道微生物群的影响较小。

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引用次数: 0

14-day tailored PCR-guided triple therapy versus 14-day non-Bismuth concomitant quadruple therapy for Helicobacter pylori eradication: A multicenter, open-label randomized noninferiority controlled trial 根除幽门螺旋杆菌的 14 天定制 PCR 指导三联疗法与 14 天非铋剂伴随四联疗法：多中心、开放标签随机非劣效性对照试验

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-04-29 DOI: 10.1111/hel.13076

Aurelien Amiot, Jérémy Hacoon, Frederic Heluwaert, François Mion, Dominique Lamarque, Driffa Moussata, Maroua Mimouni, Jean-Charles Delchier, Isabelle Durand-Zaleski, Etienne Audureau, Sylvie Bastuji-Garin, for the HEPYSE Study Group

Background

The systematic use of susceptibility testing and tailored first-line treatment for Helicobacter pylori eradication has yet to be established.

Aim

To compare 14-day tailored PCR-guided triple therapy to 14-day non-Bismuth concomitant quadruple therapy for first-line Helicobacter pylori eradication.

Patients and Methods

We performed a multicenter, parallel-group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14-day tailored PCR-guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14-day non-Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication.

Results

We screened 991 patients for eligibility and randomized 241 patients. The first-line eradication rate was 99.2% in the tailored PCR-guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at −0.68%). Both first-line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR-guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR-guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population.

Conclusion

In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14-day tailored PCR-guided triple therapy as a first-line H. pylori eradication therapy compared to 14-day non-Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236).

背景在根除幽门螺旋杆菌的一线治疗中系统地使用药敏试验和量身定制的治疗方法尚未确立。目的比较 14 天定制的 PCR 指导下的三联疗法和 14 天非铋剂同时四联疗法在一线根除幽门螺旋杆菌治疗中的效果。患者和方法我们进行了一项多中心、平行组、随机非劣效性对照试验。感染了幽门螺旋杆菌的成人患者接受了为期 14 天的定制 PCR 指导下的三联疗法（埃索美拉唑 40 毫克、阿莫西林 1000 毫克（b.d.）加克拉霉素 500 毫克或左氧氟沙星 500 毫克（b.d.根据对克拉霉素的敏感性，可选择 14 天非铋剂同时四联疗法（埃索美拉唑 40 毫克、阿莫西林 1000 毫克、克拉霉素 500 毫克和甲硝唑 500 毫克，每天两次）。主要终点是根除幽门螺杆菌。结果我们筛选了991名符合条件的患者，并对241名患者进行了随机分组。定制 PCR 指导组的一线根除率为 99.2%，对照组为 95.9%（ITT 人群；绝对差异为 +3.30%，CI 下限为 -0.68%）。两种一线疗法的耐受性都很好，定制 PCR 引导组的耐受性与对照组有显著差异（61.4% 对 41.2%，P = 0.003）。经济分析表明，定制的 PCR 指导组的成本较低，在 ITT 人群中，有 92% 的几率比对照组更有效且更便宜。结论在克拉霉素耐药性较高的国家，我们的研究结果表明，与 14 天非铋剂四联疗法（ClinicalTrials.gov NCT02576236）相比，14 天定制 PCR 指导的三联疗法作为一线幽门螺杆菌根除疗法并无劣效性。

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引用次数: 0

Prevalence of Helicobacter pylori infection among Slovenian children and adolescents: A prospective cohort study 斯洛文尼亚儿童和青少年幽门螺杆菌感染率：前瞻性队列研究

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-04-28 DOI: 10.1111/hel.13082

Anja Šterbenc, Uroš Godnov, Polona Maver Vodičar, Saša Simčič, Samo Jeverica, Živa Zaletel, Pia Homan, Eva Miler Mojškerc, Matjaž Homan

Background

Helicobacter pylori (H. pylori) infection is primarily acquired in childhood and is notably influenced by socioeconomic variances across different geographical regions. The aim of this study is to assess the prevalence of H. pylori infection in Slovenian children and to identify potential risk factors that facilitate the infection.

Materials and Methods

Between 2019 and 2022, we conducted a multi-center prospective cross-sectional study among healthy children residing in three different administrative regions in Slovenia. H. pylori infection status was determined using a monoclonal antibody-based stool antigen test (SAT). A standardized questionnaire was designed to evaluate the influence of various H. pylori-associated risk factors, including demographics and socioeconomic, housing and sanitation conditions.

Results

During the 3-year period, we recruited a total of 421 children and adolescents (age range 2–18 years, mean age 10.29 ± 4.95 years). Overall, 46 (10.9%) were diagnosed with H. pylori infection. No associations were found between H. pylori prevalence rates and increasing age, sex, parental education level, country of birth of the child or their parents, number of household members, household income, having a dishwasher, owning a pet, duration of breastfeeding, fruit intake frequency, drinking tap water, and handwashing practices. The only parameters associated with an increased risk of infection were the location of the school (p < 0.001) and living in an urban area (p = 0.036). The odds of infection were approximately 4.77 times higher if the child attended school in the Central Slovenian compared to other regions (OR = 4.77; 95% CI 0.87–2.34).

Conclusions

This is the first study providing information on the prevalence of H. pylori infection among Slovenian children and adolescents. Using SAT, we have shown that the burden of H. pylori infection in our pediatric population is low; however, it seems to depend on regional rather than socioeconomic factors.

背景幽门螺杆菌（H. pylori）感染主要发生在儿童时期，不同地区的社会经济差异对其影响显著。本研究旨在评估斯洛文尼亚儿童的幽门螺杆菌感染率，并确定导致感染的潜在风险因素。材料与方法 2019 年至 2022 年期间，我们对居住在斯洛文尼亚三个不同行政区域的健康儿童进行了一项多中心前瞻性横断面研究。幽门螺杆菌感染状况通过基于单克隆抗体的粪便抗原检测（SAT）来确定。我们设计了一份标准化问卷，以评估与幽门螺杆菌相关的各种风险因素的影响，包括人口统计学、社会经济、住房和卫生条件。结果在 3 年的时间里，我们共招募了 421 名儿童和青少年（年龄在 2-18 岁之间，平均年龄为 10.29 ± 4.95 岁）。其中 46 人（10.9%）被确诊感染幽门螺杆菌。未发现幽门螺杆菌感染率与年龄、性别、父母教育水平、儿童或其父母的出生国、家庭成员数量、家庭收入、拥有洗碗机、拥有宠物、母乳喂养时间、水果摄入频率、饮用自来水和洗手习惯之间存在关联。唯一与感染风险增加有关的参数是学校所在地（p < 0.001）和居住在城市地区（p = 0.036）。与其他地区相比，在斯洛文尼亚中部地区上学的儿童受感染的几率大约高出 4.77 倍（OR = 4.77；95% CI 0.87-2.34）。结论这是第一项关于斯洛文尼亚儿童和青少年幽门螺杆菌感染率的研究。通过使用 SAT，我们发现我国儿童幽门螺杆菌感染率较低；不过，这似乎取决于地区因素而非社会经济因素。

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引用次数: 0

Diagnostic performance of linked color imaging for gastric cancer by Helicobacter pylori infection status: A subanalysis of the large-scale, multicenter randomized controlled trial LCI-FIND 根据幽门螺旋杆菌感染状况进行胃癌联动彩色成像的诊断性能：大规模多中心随机对照试验 LCI-FIND 的子分析

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-04-26 DOI: 10.1111/hel.13080

Mototsugu Kato, Shoko Ono, Kenro Kawada, Osamu Dohi, Shinji Kitamura, Tomoyuki Koike, Shinichiro Hori, Hiromitsu Kanzaki, Takahisa Murao, Nobuaki Yagi, Fumisato Sasaki, Keiichi Hashiguchi, Shiro Oka, Kazuhiro Katada, Ryo Shimoda, Kazuhiro Mizukami, Mitsuhiko Suehiro, Toshihisa Takeuchi, Shinichi Katsuki, Momoko Tsuda, Yuji Naito, Tatsuyuki Kawano, Ken Haruma, Keita Mori, Hideki Ishikawa

Background

Linked color imaging (LCI) is a new image enhancement technology that facilitates the recognition of subtle differences in mucosal color. In the large-scale, multicenter randomized controlled trial LCI-FIND, LCI demonstrated good diagnostic performance for the detection of tumor lesions in the upper gastrointestinal tract. The aim of the present study was to exploratively evaluate the diagnostic performance of LCI according to H. pylori infection status as a subanalysis of LCI-FIND trial.

Methods

The patients were randomly allocated to receive white light imaging (WLI) first, followed by LCI (WLI group), or vice versa (LCI group), and the two groups were compared for the detection of tumors. Data from this trial were analyzed by the presence/absence of H. pylori infection and further analyzed by successful or unsuccessful eradication in the H. pylori infection group.

Results

The 752 patients in the WLI group and 750 patients in the LCI group who had participated in the LCI-FIND trial were included. In the successful eradication group, more gastric lesions were detected by primary mode in the LCI group than in the WLI group, indicating that more lesions were missed by WLI. Fisher's exact probability test for the comparison of the WLI and LCI groups yielded a p-value of 0.0068, with missed gastric lesions being detected 0.136 times (95% confidence interval: 0.020–0.923), significantly less with LCI than with WLI.

Conclusion

The current study suggests that LCI should be used for gastric cancer screening, particularly in patients with successful H. pylori eradication.

背景关联彩色成像（LCI）是一种新的图像增强技术，有助于识别粘膜颜色的细微差别。在大规模多中心随机对照试验 LCI-FIND 中，LCI 在检测上消化道肿瘤病变方面表现出良好的诊断性能。本研究的目的是作为 LCI-FIND 试验的一项子分析，根据幽门螺杆菌感染状况探索性地评估 LCI 的诊断性能。方法随机分配患者先接受白光成像（WLI），然后接受 LCI（WLI 组），或反之（LCI 组），并比较两组对肿瘤的检测情况。根据是否感染幽门螺杆菌对试验数据进行分析，并根据幽门螺杆菌感染组成功或失败根除幽门螺杆菌进行进一步分析。结果参与 LCI-FIND 试验的 752 名 WLI 组患者和 750 名 LCI 组患者被纳入其中。在成功根除组中，LCI 组通过初级模式检测到的胃部病变多于 WLI 组，这表明 WLI 遗漏了更多的病变。对 WLI 组和 LCI 组的比较进行费舍尔精确概率检验，得出的 P 值为 0.0068，漏检胃部病变的次数为 0.136 次（95% 置信区间：0.020-0.923），LCI 组明显少于 WLI 组。结论目前的研究表明，LCI 应被用于胃癌筛查，尤其是在成功根除幽门螺杆菌的患者中。

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引用次数: 0

Four cases of non-Helicobacter pylori Helicobacter-infected gastritis with duodenal spiral bacilli 四例十二指肠螺旋杆菌感染的非幽门螺旋杆菌胃炎病例

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-04-26 DOI: 10.1111/hel.13083

Hiroyuki Agawa, Toshihisa Tsukadaira, Natsuko Kobayashi, Himiko Kodaira, Hiroyoshi Ota, Takehisa Matsumoto, Kazuki Horiuchi, Tatsuya Negishi, Toshifumi Tada

Background

Non-Helicobacter pylori Helicobacter (NHPH) is rarely detected in duodenal mucosa due to its preference for slightly acidic environments. Here, we report four cases of NHPH-infected gastritis with duodenal spiral bacilli, potentially NHPH, indicating the possibility of duodenal mucosal infection.

Case Presentation

In every case, gastric mucosa showed endoscopic findings characteristic of NHPH-infected gastritis, and a mucosal biopsy was taken from the duodenal bulb; spiral bacilli were identified under microscopy using Giemsa staining. Case 1, a 46-year-old man, had diffuse spotty redness, mucosal edema, and multiple tiny erosions in the duodenal bulb, along with larger erosions in the second portion of the duodenum upon endoscopic examination. Histopathologically, moderate infiltration of mononuclear cells and neutrophils in the lamina propria and gastric epithelial metaplasia were observed. Case 2, a 54-year-old man, showed an elevated lesion, 1 cm in diameter, with multiple red spots and a few tiny erosions in the duodenal bulb. Histopathologically, mild inflammatory cell infiltration and gastric epithelial metaplasia were observed. In Case 3, a 52-year-old man, endoscopy revealed a flat elevated lesion, 7 mm in diameter, with multiple red spots and a few tiny erosions in the anterior wall of the duodenal bulb. Histopathologically, we observed moderate inflammatory cell infiltration in the gastric antrum and gastric epithelial metaplasia in the duodenal bulb. Case 4, a 40-year-old man, showed mild spotty redness in the duodenal bulb. Histopathologically, mild mononucleocyte infiltration and gastric epithelial metaplasia were observed. A single spiral bacillus was observed in Case 4 by microscopy. In all but Case 2, Helicobacter suis was identified in the gastric juice by polymerase chain reaction analysis.

Conclusions

Spiral bacilli resembling NHPH may infect the duodenal mucosa, particularly the bulb, causing inflammation. Gastric contents entering the duodenum may reduce the intraduodenal pH, promoting NHPH survival and proliferation.

背景非幽门螺旋杆菌（NHPH）由于喜欢微酸性环境，很少在十二指肠粘膜中被发现。在此，我们报告了四例 NHPH 感染性胃炎病例，其十二指肠螺旋杆菌可能是 NHPH，这表明十二指肠粘膜感染的可能性很大。病例表现每个病例的胃黏膜都显示出 NHPH 感染性胃炎的内镜特征，并从十二指肠球部取黏膜活检；使用 Giemsa 染色法在显微镜下鉴定出螺旋状杆菌。病例 1 是一名 46 岁的男性，内镜检查时发现十二指肠球部弥漫性点状发红、粘膜水肿和多处微小糜烂，十二指肠的第二部分也有较大糜烂。组织病理学检查发现，固有层有中度的单核细胞和中性粒细胞浸润，胃上皮变性。病例 2 是一名 54 岁的男性，十二指肠球部有一个直径 1 厘米的隆起病灶，病灶上有多个红点和一些微小的糜烂。组织病理学观察到轻度炎性细胞浸润和胃上皮化生。病例 3 是一名 52 岁的男性，内镜检查发现十二指肠球部前壁有一个扁平隆起的病变，直径 7 毫米，有多个红点和一些微小的糜烂。组织病理学检查发现，胃窦部有中度炎症细胞浸润，十二指肠球部有胃上皮化生。病例 4：40 岁男性，十二指肠球部轻度点状发红。组织病理学观察到轻度单核细胞浸润和胃上皮化生。病例 4 在显微镜下观察到一个螺旋状杆菌。通过聚合酶链反应分析，除病例 2 外，其他病例的胃液中都发现了猪螺旋杆菌。结论类似于 NHPH 的螺旋杆菌可能会感染十二指肠粘膜，尤其是球部，从而引起炎症。进入十二指肠的胃内容物可能会降低十二指肠内的 pH 值，促进 NHPH 的存活和增殖。

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引用次数: 0

The role of microbiota in gastric cancer: A comprehensive review 微生物群在胃癌中的作用：全面回顾

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-04-20 DOI: 10.1111/hel.13071

Changzhen Lei, Yitian Xu, Shaopeng Zhang, Chen Huang, Jing Qin

Background

Gastric cancer (GC) continues to pose a significant global threat in terms of cancer-related fatalities. Despite notable advancements in medical research and therapies, further investigation is warranted to elucidate its underlying etiology and risk factors. Recent times have witnessed an escalated emphasis on comprehending the role of the microbiota in cancer development.

Methods

This review briefly delves into recent developments in microbiome-related research pertaining to gastric cancer.

Results

According to studies, the microbiota can influence GC growth by inciting inflammation, disrupting immunological processes, and generating harmful microbial metabolites. Furthermore, there is ongoing research into how the microbiome can impact a patient's response to chemotherapy and immunotherapy.

Conclusion

The utilization of the microbiome for detecting, preventing, and managing stomach cancer remains an active area of exploration.

背景胃癌（GC）仍然是全球癌症相关死亡的重大威胁。尽管医学研究和疗法取得了显著进展，但仍需进一步调查以阐明其潜在病因和风险因素。近来，人们越来越重视了解微生物群在癌症发展中的作用。方法本综述简要探讨与胃癌有关的微生物群相关研究的最新进展。结果根据研究，微生物群可通过诱发炎症、干扰免疫过程和产生有害的微生物代谢产物来影响胃癌的生长。此外，有关微生物群如何影响患者对化疗和免疫疗法的反应的研究也在进行中。结论利用微生物组检测、预防和管理胃癌仍是一个积极探索的领域。

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引用次数: 0

Evaluating the potency of zoliflodacin against Helicobacter pylori: In vitro activity and conserved GyrB target 评估佐利氟达星抗幽门螺旋杆菌的效力：体外活性和保守的 GyrB 靶点

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-04-16 DOI: 10.1111/hel.13075

Jing Liu, Jia Jia, Ting Shi, Yuefan Bai, Yanqiang Huang, Liping Zeng, Hongkai Bi

Background

The current standard treatment for Helicobacter pylori infection, which involves a combination of two broad-spectrum antibiotics, faces significant challenges due to its detrimental impact on the gut microbiota and the emergence of drug-resistant strains. This underscores the urgent requirement for the development of novel anti-H. pylori drugs. Zoliflodacin, a novel bacterial gyrase inhibitor, is currently undergoing global phase III clinical trials for treating uncomplicated Neisseria gonorrhoeae. However, there is no available data regarding its activity against H. pylori.

Materials and Methods

We evaluated the in vitro activity of zoliflodacin against H. pylori clinical isolates (n = 123) with diverse multidrug resistance. We performed DNA gyrase supercoiling and microscale thermophoresis assays to identify the target of zoliflodacin in H. pylori. We analyzed 2262 H. pylori whole genome sequences to identify Asp424Asn and Lys445Asn mutations in DNA gyrase subunit B (GyrB) that are associated with zoliflodacin resistance.

Results

Zoliflodacin exhibits potent activity against all tested isolates, with minimal inhibitory concentration (MIC) values ranging from 0.008 to 1 μg/mL (MIC₅₀: 0.125 μg/mL; MIC₉₀: 0.25 μg/mL). Importantly, there was no evidence of cross-resistance to any of the four first-line antibiotics commonly used against H. pylori. We identified GyrB as the primary target of zoliflodacin, with Asp424Asn or Lys445Asn substitutions conferring resistance. Screening of 2262 available H. pylori genomes for the two mutations revealed only one clinical isolate carrying Asp424Asn substitution.

Conclusion

These findings support the potential of zoliflodacin as a promising candidate for H. pylori treatment, warranting further development and evaluation.

背景幽门螺旋杆菌感染目前的标准治疗方法是联合使用两种广谱抗生素，但由于这种方法对肠道微生物群的有害影响以及耐药菌株的出现，这种方法面临着巨大的挑战。这凸显了开发新型抗幽门螺杆菌药物的迫切需求。新型细菌回旋酶抑制剂 Zoliflodacin 目前正在全球进行 III 期临床试验，用于治疗无并发症的淋病奈瑟菌。然而，目前还没有关于它对幽门螺杆菌活性的数据。材料与方法我们评估了佐利氟达星对具有多种耐药性的幽门螺杆菌临床分离株（n = 123）的体外活性。我们进行了DNA回旋酶超螺旋和微尺度热泳检测，以确定佐利氟达星在幽门螺杆菌中的靶点。我们分析了2262个幽门螺杆菌全基因组序列，以确定DNA回旋酶亚基B（GyrB）中与佐利氟达星耐药性相关的Asp424Asn和Lys445Asn突变。结果佐利氟达星对所有测试的分离菌株都具有强效活性，最小抑菌浓度 (MIC) 值范围为 0.008 至 1 μg/mL（MIC50：0.125 μg/mL；MIC90：0.25 μg/mL）。重要的是，没有证据表明幽门螺杆菌对常用的四种一线抗生素产生交叉耐药性。我们发现GyrB是佐利氟达星的主要作用靶点，Asp424Asn或Lys445Asn取代可产生抗药性。对现有的 2262 个幽门螺杆菌基因组进行这两种突变筛查后发现，只有一个临床分离株携带 Asp424Asn 取代。结论这些发现支持了佐立氟达辛作为幽门螺杆菌治疗候选药物的潜力，值得进一步开发和评估。

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引用次数: 0

A reconstructed genome-scale metabolic model of Helicobacter pylori for predicting putative drug targets in clarithromycin and rifampicin resistance conditions 重建幽门螺旋杆菌基因组尺度代谢模型，用于预测克拉霉素和利福平耐药性条件下的可能药物靶点

IF 4.4 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Helicobacter

Pub Date : 2024-04-14 DOI: 10.1111/hel.13074

Sepideh Mofidifar, Abbas Yadegar, Mohammad Hossein Karimi-Jafari

Background

Helicobacter pylori is considered a true human pathogen for which rising drug resistance constitutes a drastic concern globally. The present study aimed to reconstruct a genome-scale metabolic model (GSMM) to decipher the metabolic capability of H. pylori strains in response to clarithromycin and rifampicin along with identification of novel drug targets.

Materials and Methods

The iIT341 model of H. pylori was updated based on genome annotation data, and biochemical knowledge from literature and databases. Context-specific models were generated by integrating the transcriptomic data of clarithromycin and rifampicin resistance into the model. Flux balance analysis was employed for identifying essential genes in each strain, which were further prioritized upon being nonhomologs to humans, virulence factor analysis, druggability, and broad-spectrum analysis. Additionally, metabolic differences between sensitive and resistant strains were also investigated based on flux variability analysis and pathway enrichment analysis of transcriptomic data.

Results

The reconstructed GSMM was named as HpM485 model. Pathway enrichment and flux variability analyses demonstrated reduced activity in the ribosomal pathway in both clarithromycin- and rifampicin-resistant strains. Also, a significant decrease was detected in the activity of metabolic pathways of clarithromycin-resistant strain. Moreover, 23 and 16 essential genes were exclusively detected in clarithromycin- and rifampicin-resistant strains, respectively. Based on prioritization analysis, cyclopropane fatty acid synthase and phosphoenolpyruvate synthase were identified as putative drug targets in clarithromycin- and rifampicin-resistant strains, respectively.

Conclusions

We present a robust and reliable metabolic model of H. pylori. This model can predict novel drug targets to combat drug resistance and explore the metabolic capability of H. pylori in various conditions.

背景幽门螺旋杆菌被认为是一种真正的人类病原体，其耐药性的不断增加是全球范围内的一个严重问题。本研究旨在重建一个基因组规模的代谢模型（GSMM），以解读幽门螺杆菌菌株对克拉霉素和利福平的代谢能力，同时鉴定新的药物靶点。材料与方法根据基因组注释数据以及文献和数据库中的生化知识更新了幽门螺杆菌的 iIT341 模型。通过将克拉霉素和利福平耐药性的转录组数据整合到模型中，生成了针对特定环境的模型。通量平衡分析用于识别每个菌株中的重要基因，这些基因在与人类非同源、毒力因子分析、可药性和广谱分析的基础上被进一步优先排序。此外，还根据转录组数据的通量变异分析和通路富集分析，研究了敏感菌株和抗性菌株之间的代谢差异。结果重建的 GSMM 被命名为 HpM485 模型。通路富集和通量变异分析表明，克拉霉素耐药菌株和利福平耐药菌株的核糖体通路活性均有所降低。此外，耐克拉霉素菌株的代谢途径活性也明显下降。此外，在克拉霉素耐药菌株和利福平耐药菌株中分别检测到 23 个和 16 个必需基因。根据优先级分析，环丙烷脂肪酸合成酶和磷酸烯醇丙酮酸合成酶分别被确定为克拉霉素耐药菌株和利福平耐药菌株的潜在药物靶点。结论我们提出了一个稳健可靠的幽门螺杆菌代谢模型。该模型可预测新的药物靶点以对抗耐药性，并探索幽门螺杆菌在各种条件下的代谢能力。

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引用次数: 0