AbstractHelicobacter pylori is a prevalent bacterial pathogen globally, implicated in various gastrointestinal disorders. Current recommended antibiotic therapies for H. pylori infection have been proven to be therapeutically insufficient, with low eradication rates and high recurrence rates. Emerging evidence suggests that antibiotic therapy for H.

摘要幽门螺杆菌是全球流行的细菌病原体，与各种胃肠道疾病有关。目前推荐的幽门螺杆菌感染抗生素治疗已被证明在治疗上不足，根除率低，复发率高。新出现的证据表明，H的抗生素治疗。

pylori can lead to gastrointestinal and subsequent vaginal dysbiosis, posing challenges for conventional antibiotic approaches. Thus, this article proposes a novel probiotic therapy involving simultaneous oral and intra-vaginal probiotic administration alongside antibiotics for H. pylori treatment, aiming to enhance eradication rates and mitigate dysbiosis.

幽门螺杆菌可导致胃肠道和随后的阴道生态失调，对常规抗生素方法构成挑战。因此，本文提出了一种新型益生菌疗法，包括同时口服和阴道内益生菌以及用于幽门螺杆菌治疗的抗生素，旨在提高根除率并减轻生态失调。

We begin by providing an overview of gastrointestinal and vaginal microbiota and their interconnectedness through the vagina-gut axis. We then review the efficacy of current antibiotic regimens for H. pylori and discuss how antibiotic treatment impacts the vaginal microenvironment. To explore the feasibility of this approach, we evaluate the effectiveness of oral and intra-vaginal probiotics in restoring normal microbiota in the gastrointestinal and vaginal tracts, respectively.

我们首先概述胃肠道和阴道微生物群及其通过阴道-肠道轴的相互关系。然后，我们回顾了目前抗生素治疗幽门螺杆菌的疗效，并讨论了抗生素治疗如何影响阴道微环境。为了探索这种方法的可行性，我们评估了口服和阴道内益生菌分别恢复胃肠道和阴道正常微生物群的有效性。

Additionally, we analyze the direct mechanisms by which oral and intra-vaginal probiotics act on their respective tracts and discuss potential cross-tract mechanisms. Considering the potential synergistic therapeutic effects of probiotics in both the gastrointestinal and vaginal tracts, dual-channel probiotic therapy holds promise as a more effective approach for H.

此外，我们分析了口服和阴道内益生菌作用于各自肠道的直接机制，并讨论了潜在的跨肠道机制。考虑到益生菌在胃肠道和阴道道中的潜在协同治疗作用，双通道益生菌疗法有望成为治疗H的更有效方法。

pylori eradication and dysbiosis mitigation, presenting a novel concept in the collaborative treatment of gastrointestinal and genital disorders..

根除幽门螺杆菌和缓解生态失调，为胃肠道和生殖器疾病的协同治疗提供了一个新概念。。

IntroductionHelicobacter pylori, a gram-negative pathogenic bacterium, colonizes the gastrointestinal (GI) tract and is classified as a class I carcinogen by the International Agency for Research on Cancer (IARC), representing a major contributor to gastric cancer1. H. pylori infection is widespread in human population and its morbidity reaches 20% to 30% in developed areas, while in economically underdeveloped countries, the prevalence can be higher than 50%2.

简介幽门螺杆菌（Helicobacter pylori）是一种革兰氏阴性致病细菌，在胃肠道（GI）中定殖，被国际癌症研究机构（IARC）归类为I类致癌物，是胃癌的主要贡献者1。H、 幽门螺杆菌感染在人群中广泛存在，在发达地区其发病率达到20%至30%，而在经济不发达国家，患病率可能高于50%2。

Studies have consistently shown that H. pylori can initiate chronic active gastritis in nearly all infected individuals, which may progress to peptic ulceration or gastric fibrosis3. Moreover, persistent infection significantly elevates the risk of developing precancerous lesions such as atrophic gastritis by approximately nine-fold, along with an eight-fold increase in the risk of actual carcinogenesis4.Combinations of multiple antibiotic agents (clarithromycin, amoxicillin, and metronidazole) and proton pump inhibitors (PPIs) are widely used in the current regimen for H.

研究一致表明，幽门螺杆菌几乎可以在所有感染者中引发慢性活动性胃炎，这可能会发展为消化性溃疡或胃纤维化3。此外，持续感染显着提高了发生癌前病变（如萎缩性胃炎）的风险约9倍，同时实际致癌风险增加了8倍4。多种抗生素（克拉霉素，阿莫西林和甲硝唑）和质子泵抑制剂（PPIs）的组合广泛用于目前的H方案。

pylori infection as first-line treatment5. The most commonly employed eradication therapies are triple or quadruple antibiotic regimens, which have demonstrated favorable clinical outcomes with an average eradication rate of 80% to 87%6. However, the overuse of antibiotics has led to several issues, including reduced efficacy of antibiotic treatment due to the escalation of drug resistance and a high recurrence rate7.

。最常用的根除疗法是三重或四重抗生素方案，已显示出良好的临床结果，平均根除率为80%至87%6。然而，抗生素的过度使用导致了几个问题，包括由于耐药性升级和高复发率导致抗生素治疗效果降低7。

Systemic antibiotic therapy can also be correlated with various side effects, such as allergic reactions, gastrointestinal symptoms, and gastrointestinal dysbiosis8. Additionally, the indiscriminate antimicrobial effect can further negatively impact the beneficial microbiota residing in other anatomical sites, leading to overall d.

全身抗生素治疗也可能与各种副作用相关，如过敏反应，胃肠道症状和胃肠道生态失调8。此外，不加区分的抗菌作用可能会进一步对居住在其他解剖部位的有益微生物群产生负面影响，从而导致整体d。

Helicobacter pylori infection and its current eradication therapyH. pylori was initially identified by Marshall and Warren in 1984 through observation of antral mucosa tissue sections from a patient with chronic gastritis37. Upon noticing the presence of inflammation in the adjacent gastric mucosa, Warren hypothesized that H.

幽门螺杆菌感染及其目前的根除治疗。。当注意到邻近胃粘膜存在炎症时，沃伦假设H。

pylori might be closely associated with the incidence of gastritis. In the majority of cases, initial complications resulting from H. pylori infection typically lead to mild pangastritis, which does not significantly affect gastric physiology or lead to severe diseases38. However, H. pylori can establish persistent infection in the acidic environment of the gastric mucosa due to its unique residing characteristics, such as paralogous outer membrane proteins (OMPs)39 and the combination of urase and urea channel (UreI)40.

幽门螺杆菌可能与胃炎的发病率密切相关。在大多数情况下，由幽门螺杆菌感染引起的初始并发症通常会导致轻度泛胃肠炎，这不会显着影响胃生理或导致严重疾病38。然而，幽门螺杆菌由于其独特的居住特征，如旁系同源外膜蛋白（OMPs）39和尿酸酶和尿素通道（UreI）40的组合，可以在胃粘膜的酸性环境中建立持续感染。

If left untreated, persistent infection can progress to antral predominant gastritis41, chronic non-atrophic gastritis42, and even atrophic gastritis43, which is considered a major precancerous lesion for gastric cancer. Further progression depends on the virulence of pathogenic strains, such as the cag-pathogenicity island (cag-PAI)44.

如果不及时治疗，持续感染可发展为胃窦占优势的胃炎41，慢性非萎缩性胃炎42，甚至萎缩性胃炎43，这被认为是胃癌的主要癌前病变。进一步的进展取决于致病菌株的毒力，例如cag致病岛（cag PAI）44。

Expression of Cag-PAI genes can lead to the deterioration of normal gastric epithelium and ultimately result in intestinal metaplasia. These developments may gradually progress into noninvasive neoplasia, high-grade dysplasia, and eventually invasive malignant gastric carcinoma, which can be extremely harmful and even fatal45.In 2007, the American College of Gastroenterology Guideline proposed standard triple therapy as the first-line regimen for H.

Cag-PAI基因的表达可导致正常胃上皮的恶化并最终导致肠化生。这些发展可能逐渐发展为非侵袭性肿瘤，高度不典型增生，最终发展为侵袭性恶性胃癌，这可能是极其有害甚至致命的45。2007年，美国胃肠病学会指南提出标准三联疗法作为H的一线方案。

pylori infection, consisting of a proton pump inhibitor (PPI)46 and two other antibacterial agents (clarithromycin and amoxicillin) for a 2-weeks course.

幽门螺杆菌感染，由质子泵抑制剂（PPI）46和其他两种抗菌剂（克拉霉素和阿莫西林）组成，为期2周。

Helicobacter pylori infection and eradication affect gastrointestinal microbiomesIt has been reported that H. pylori infection can alter the diversity of the intestinal microbiota54. This may be due to changes in the pH of the gastrointestinal caused by H. pylori infection, leading to damage and invasion of the gastrointestinal mucosa.

幽门螺杆菌感染和根除影响胃肠道微生物群据报道，幽门螺杆菌感染可改变肠道微生物群的多样性54。这可能是由于幽门螺杆菌感染引起的胃肠道pH值变化，导致胃肠粘膜受损和侵袭。

Further, compromised gastric mucosa may increase the adhesion and migration of immune cells, ultimately resulting in the inability of the original gastrointestinal microbiota to survive55. From one clinical trial, the gut microbial diversity was significantly reduced in individuals infected with H. pylori compared to healthy individuals, with significantly decreased abundance of Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, Gemmatimonadetes, and Verrucomicrobia.

此外，受损的胃粘膜可能会增加免疫细胞的粘附和迁移，最终导致原始胃肠道微生物群无法存活55。从一项临床试验来看，与健康个体相比，感染幽门螺杆菌的个体的肠道微生物多样性显着降低，放线菌，拟杆菌，厚壁菌，梭杆菌，Gemmatimonadetes和Verrucomicrobia的丰度显着降低。

Additionally, eight genera were significantly more abundant in healthy individuals compared to those with H. pylori infection, including Achromobacter, Devosia, Halomonas, Mycobacterium, Pseudomonas, Serratia, Sphingopyxis, and Stenotrophomonas56. Moreover, another study reported a reversal in gastric microbial abundance at the phylum level.

此外，与幽门螺杆菌感染者相比，健康个体中有8个属显着更丰富，包括无色杆菌，Devosia，Halomonas，分枝杆菌，假单胞菌，沙雷氏菌，鞘氨醇增多症和狭窄单胞菌56。此外，另一项研究报道了门水平上胃微生物丰度的逆转。

Reduced bacterial diversity was observed in H. pylori subjects, with Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria being the most abundant phyla, whereas in normal subjects, the most abundant phyla were Bacteroidetes, Firmicutes, Actinobacteria, and Proteobacteria57. These alterations in the gastrointestinal microbiota, driven by H.

在幽门螺杆菌受试者中观察到细菌多样性降低，Proteobacteria，Firmicutes，Bacteroidetes和Actinobacteria是最丰富的门，而在正常受试者中，最丰富的门是Bacteroidetes，Firmicutes，Actinobacteria和Proteobacteria57。由H驱动的胃肠道微生物群的这些改变。

pylori infection, may lead to the progression of gut dysbiosis.Another implicated issue of gut dysbiosis is provoked by the indiscriminate antimicrobial effects of H. pylori eradication therapy58. Both antibiotics and PPIs used for H. pylori eradication may significantly impact the gut mi.

幽门螺杆菌感染，可能导致肠道生态失调的进展。幽门螺杆菌根除治疗的不分青红皂白的抗菌作用引起了肠道生态失调的另一个牵连问题58。用于根除幽门螺杆菌的抗生素和PPI都可能显着影响肠道mi。

Helicobacter pylori eradication therapy and vaginal dysbacteriosisEvidence of Helicobacter pylori antimicrobial therapy induced vaginal dysbiosisIn addition to gastrointestinal microbiomes, the antimicrobial effects of antibiotics could also affect the microbial communities in skin63, respiratory64, and vagina65.

幽门螺杆菌根除治疗和阴道菌群失调幽门螺杆菌抗菌治疗诱导阴道菌群失调的证据除了胃肠道微生物群外，抗生素的抗菌作用还可能影响皮肤63，呼吸道64和阴道65中的微生物群落。

Antibiotics used to treat H. pylori infections typically aim to eradicate bacterial colonization but without specifically targeting particular microbiomes. Due to their broad antimicrobial spectrum, these antibiotics may have off-target effects, resulting in concentrations exceeding what is necessary for eliminating pathogenic H.

用于治疗幽门螺杆菌感染的抗生素通常旨在根除细菌定植，但不专门针对特定的微生物组。由于其广泛的抗菌谱，这些抗生素可能具有脱靶作用，导致浓度超过消除致病性H所必需的浓度。

pylori. Consequently, they could disrupt and imbalance the normal body microbiota, reducing colonization resistance for an extended period following administration66.A clinical study by Kravtsov et al.12 aimed to investigate the possibility of an increased risk of candidiasis in the female genital tract after H.

幽门螺杆菌。因此，它们可能破坏和失衡正常的身体微生物群，在给药后长时间降低定植抗性66。Kravtsov等人12的一项临床研究旨在调查H后女性生殖道念珠菌病风险增加的可能性。

pylori eradication therapy. They reported that following a 2-week quadruple bismuth therapy (consisting of rabeprazole, amoxicillin, tetracycline, and bismuthate tripotassium dicitrate), elements of Candida fungus were found in smears taken from the cervix uteri and lateral vaginal vault in all patients.

幽门螺杆菌根除治疗。他们报告说，经过为期2周的四联铋疗法（由雷贝拉唑，阿莫西林，四环素和铋酸三钾二硝酸盐组成）后，在所有患者的子宫颈和阴道外侧穹窿涂片中发现了念珠菌的成分。

Approximately 22% of patients administered anti-helicobacter therapy were diagnosed with Candida vulvovaginitis, indicating an increased incidence of vaginal dysbiosis after H. pylori eradication. Further investigation revealed significantly elevated levels of cytokines IL-8 and TNF-α in vaginal secretions from patients treated with anti-helicobacter therapy compared to those without antibiotic administration67.

大约22%接受抗螺杆菌治疗的患者被诊断出患有念珠菌外阴阴道炎，表明根除幽门螺杆菌后阴道生态失调的发生率增加。进一步的研究表明，与未服用抗生素的患者相比，接受抗螺杆菌治疗的患者阴道分泌物中细胞因子IL-8和TNF-α水平显着升高67。

This suggests that H. pylori eradication treatment may strongly disrupt the immune status of the female vaginal tract.

这表明根除幽门螺杆菌治疗可能会强烈破坏女性阴道道的免疫状态。

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Download referencesAcknowledgementsSincere gratitude to T.C., Z.Z., and Q.C. for their selfless guidance on the conceptualization and writing structure of this article. Many thanks to the lab colleagues for their valuable suggestions on paper collection and writing. This work was supported by grants from the National Natural Science Foundation of China (Grant No.

下载参考文献致谢衷心感谢T.C.，Z.Z。和Q.C.对本文概念化和写作结构的无私指导。非常感谢实验室同事在论文收集和写作方面提出的宝贵建议。这项工作得到了国家自然科学基金（批准号：。

82060638) and the Double Thousand Plan of Jiangxi Province (High-End Talents Project of Scientific and Technological Innovation). Figures were created using BioRender software (biorender.com).Author informationAuthors and AffiliationsDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, ChinaYufan Wang, Qi Chen & Tingtao ChenQueen Mary School, Jiangxi Medical College, Nanchang University, Nanchang, 330031, ChinaYufan WangNational Engineering Research Centre for Bioengineering Drugs and Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, 330031, ChinaYufan Wang & Tingtao ChenDepartment of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, ChinaZhenyu ZhangSchool of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, 330031, ChinaTingtao ChenAuthorsYufan WangView author publicationsYou can also search for this author in.

82060638）和江西省双千计划（科技创新高端人才项目）。数字是使用BioRender软件（BioRender.com）创建的。作者信息作者和附属机构南昌大学江西医学院第二附属医院妇产科，江西南昌，330006，中国王玉凡，陈琦和陈廷涛，江西医学院，南昌大学，南昌，330031，中国王玉凡，江西医学院转化医学研究所，江西医学院，南昌，330031，中国王玉凡和陈廷涛南京医科大学南京第一医院消化内科，南京，中国张振宇药学院，江西医学院，南昌，330031，中国陈廷涛作者王玉凡。。。的信息。。。的作者信息。的来源于中国医学院，江西医学院，南昌，330031，中国王玉凡，陈廷涛，中国医学院，南京第一医院，南京，张振宇药学院，南昌，南昌，南昌，330031，中国王玉凡，陈廷涛。

PubMed Google ScholarZhenyu ZhangView author publicationsYou can also search for this author in

PubMed谷歌学者张振宇查看作者出版物您也可以在

PubMed Google ScholarQi ChenView author publicationsYou can also search for this author in

PubMed Google ScholarQi ChenView作者出版物您也可以在

PubMed Google ScholarTingtao ChenView author publicationsYou can also search for this author in

PubMed Google ScholarTingtao ChenView作者出版物您也可以在

PubMed Google ScholarContributionsConceptualization: T.C., Z.Z., Q.C., and Y.W.; writing-original draft, Y.W.; writing-review and editing, T.C., Z.Z., Q.C., and Y.W. All authors have read and agreed to the published version of the manuscript.Corresponding authorsCorrespondence to.

PubMed谷歌学术贡献概念：T.C.，Z.Z.，Q.C。和Y.W。；撰写原稿，Y.W。；写作评论和编辑，T.C.，Z.Z.，Q.C。和Y.W。所有作者都阅读并同意稿件的出版版本。通讯作者通讯。

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Reprints and permissionsAbout this articleCite this articleWang, Y., Zhang, Z., Chen, Q. et al. Simultaneous application of oral and intravaginal probiotics for Helicobacter pylori and its antibiotic-therapy-induced vaginal dysbacteriosis.

转载和许可本文引用本文Wang，Y.，Zhang，Z.，Chen，Q。等人。口服和阴道内益生菌同时应用于幽门螺杆菌及其抗生素治疗引起的阴道菌群失调。

npj Biofilms Microbiomes 10, 49 (2024). https://doi.org/10.1038/s41522-024-00521-9Download citationReceived: 19 July 2023Accepted: 07 June 2024Published: 20 June 2024DOI: https://doi.org/10.1038/s41522-024-00521-9Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

npj生物膜微生物组10,49（2024）。https://doi.org/10.1038/s41522-024-00521-9Download引文接收日期：2023年7月19日接收日期：2024年6月7日发布日期：2024年6月20日OI：https://doi.org/10.1038/s41522-024-00521-9Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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