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H. pylori infection is the strongest known risk factor for gastric carcinoma. The activation of the yes-associated protein 1 (YAP) and β-catenin pathways has been associated with multiple tumor types. In this study, we investigated the crosstalk between the YAP and β-catenin pathways in H. pylori -associated gastric tumorigenesis. Immunohistochemical analysis of YAP and β-catenin expression was performed in human gastric cancer tissues. The small molecules Super-TDU and KYA1797K, pharmacological inhibitors of YAP and β-catenin, respectively, were used to investigate the role of these signaling pathways in H. pylori -induced gastric carcinogenesis in murine models of infection. The common downstream targets of YAP and β-catenin signaling were evaluated by RNA sequencing (RNA-seq). Western blot, immunofluorescence, luciferase, RT-PCR, immunoprecipitation, cell counting kit-8 (CCK8), EdU and spheroid assays were used. H. pylori infection promoted YAP and β-catenin nuclear accumulation and transcriptional activity in gastric epithelial cells and transgenic insulin-gastrin (INS-GAS) mice, whereas silencing of both YAP and β-catenin synergistically inhibited H. pylori- induced cell proliferation and expansion. In addition, YAP was found to directly interact with β-catenin and knockdown of YAP suppressed H. pylori -induced nuclear translocation of β-catenin. Moreover, downstream genes caudal-type homeobox 2 (CDX2), leucine-rich repeat containing G protein-coupled receptor 5 (LGR5) and RuvB like AAA ATPase 1 (RUVBL1) were shared by both YAP and β-catenin signaling. Furthermore, treatment with the YAP inhibitor Super-TDU or β-catenin inhibitor KYA1797A significantly alleviated gastric inflammation and epithelial DNA damage in H. pylori -infected mice. Finally, the elevation of gastric YAP was positively correlated with β-catenin expression in human gastric cancer tissues. These findings indicate that YAP and β-catenin synergistically promote H. pylori -induced gastric carcinogenesis via their physical interaction and reveal that CDX2, LGR5 and RUVBL1 are the downstream genes shared by both the YAP and β-catenin signaling pathways, and potentially contribute to H. pylori pathogenesis.

Background: The aim of this current study was to identify the prevalence and risk factors of H. pylori infection in the low-risk area of gastric cancer in China, and evaluate the value of different gastric cancer screening methods., Methods: An epidemiological study was conducted in Yudu County, Jiangxi, China, and participants were followed up for 6 years. All participants completed a questionnaire, laboratory tests and endoscopy. Patients were divided into H. pylori positive and negative groups, and risk factors for H. pylori infection were identified using multivariate logistic regression analysis., Results: A total of 1962 residents were included, the prevalence of H. pylori infection was 33.8%. Multivariate analysis showed that annual income ≤20,000 yuan (OR: 1.44, 95% CI: 1.18-1.77, p  < 0.001), loss of appetite (OR: 1.71, 95% CI: 1.29-2.26, p  < 0.001), PG II >37.23 ng/mL (OR: 2.11, 95% CI: 1.50-2.97, p  < 0.001), G-17 > 1.5 and ≤5.7 pmol/L (OR: 2.52, 95% CI: 1.93-3.30, p  < 0.001), and G-17 > 5.7 pmol/L (OR: 1.96, 95% CI: 1.48-2.60, p  < 0.001) were risk factors of H. pylori infection, while alcohol consumption (OR: 0.70, 95% CI: 0.54-0.91, p  = 0.006) was a protective factor. According to the new gastric cancer screening method, the prevalence of low-grade intraepithelial neoplasia in the low-risk group, medium-risk group and high-risk group was 4.4%, 7.7% and 12.5% respectively ( p  < 0.001)., Conclusions: In a low-risk area of gastric cancer in China, the infection rate of H. pylori is relatively low. Low income, loss of appetite, high PG II, and high G-17 were risk factors for H. pylori infection, while alcohol consumption was a protective factor. Moreover, the new gastric cancer screening method better predicted low-grade intraepithelial neoplasia than the ABC method and the new ABC method.

Background: Helicobacter pylori ( H. pylori ) eradication has been reported to cause short-term disruption of gut microbiota. It is acknowledged that probiotics supplementation mitigates side effects induced by H. pylori eradication, yet its role on alleviating dysbiosis of microbiota is obscure., Objectives: To evaluate the impact of probiotics on gastrointestinal microbiota after eradication therapy., Methods: This was a multicenter, double-blinded, randomized trial done at seven centers in China. A total of 276 treatment-naïve H. pylori -positive patients were randomly assigned to receive 14-day bismuth-containing quadruple therapy (esomeprazole, bismuth, amoxicillin, furazolidone) combined with probiotics (Bifidobacterium Tetragenous viable Bacteria Tablets) (n=140) or placebo (n=136) for 28 days. Saliva, gastric mucosa and fecal samples were collected before and after therapy for 16S rRNA gene sequencing., Results: The incidence of gastrointestinal adverse events was lower in probiotics group compared to placebo group (23.6% vs 37.7%, p=0.016), while there was no significant difference in eradication rate. We found dramatic perturbations of gut microbiota immediately following eradication, with the predominance of Proteobacteria in replacement of commensal Firmicutes and Bacteroidetes, and gradually restored after two weeks. The reduction of gut Bacteroidetes caused by eradication drugs was neutralized with probiotics supplementation. The gastric microbiota was completely reconstituted with H. pylori depleted and other taxa flourished. Of note, patients treated with probiotics showed smaller fluctuations of gastric microbiota compared to those with placebo. We also observed changes of saliva microbiota after H. pylori eradication, illustrated by the overgrowth of Neisseria and depletion of Streptococcus . The expansion of some pathogenic genera, including Porphyromonas , Leptotrichia , in the mouth was suppressed by probiotics., Conclusion: This study not only demonstrated the beneficial effect of probiotics implementation on side events during H. pylori eradication but also provided a comprehensive profile of microbiome alterations along gastrointestinal tract that modulated by probiotics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 He, Xie, Zhu, Zhuang, Huo, Yu, Guo, Shu, Xiong, Zhang, Lyu and Lu.)

Background: A complex microbiota in the gastric mucosa (GM) has been unveiled recently and its dysbiosis is identified to be associated with gastric cancer (GC). However, the microbial composition in gastric fluid (GF) and its correlation with GM during gastric carcinogenesis are unclear., Methods: We obtained GM and GF samples from 180 patients, including 61 superficial gastritis (SG), 55 intestinal metaplasia (IM) and 64 GC and performed 16S rRNA gene sequencing analysis. The concentration of gastric acid and metabolite nitrite has been measured., Results: Overall, the composition of microbiome in GM was distinct from GF with less diversity, and both were influenced by H. pylori infection. The structure of microbiota changed differentially in GM and GF across histological stages of GC, accompanied with decreased gastric acid and increased carcinogenic nitrite. The classifiers of GC based on microbial markers were identified in both GM and GF, including Lactobacillus, Veillonella, Gemella, and were further validated in an independent cohort with good performance. Interestingly, paired comparison between GM and GF showed that their compositional distinction remarkably dwindled from SG to GC, with some GF-enriched bacteria significantly increased in GM. Moreover, stronger interaction network between microbes of GM and GF was observed in GC compared to SG., Conclusion: Our results, for the first time, revealed a comprehensive profile of both GM and GF microbiomes during the development of GC. The convergent microbial characteristics between GM and GF in GC suggest that the colonization of carcinogenic microbes in GM might derive from GF., (© 2022. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background: Dysbiosis of gastric microbiota including Helicobacter pylori (H. pylori) infection is associated with the development of stomach cancer. Probiotics have been shown to attenuate H. pylori-induced gastritis, although their role in cancer prevention remains unclear. Thus, we aimed to explore the effects of probiotics on H. pylori-induced carcinogenesis and the alterations of gastrointestinal microbiota., Methods: Male INS-GAS mice were randomly allocated to H. pylori-infected and non-infected groups. After 4 weeks, probiotic combination (containing Lactobacillus salivarius and Lactobacillus rhamnosus) was administered in drinking water for 12 weeks. Stomachs were collected for RNA-Sequencing and the differentially expressed genes were validated using RT profiler PCR array. 16S rRNA gene sequencing was performed to assess the alterations of gastrointestinal microbiota., Results: Probiotics significantly alleviate H. pylori-induced gastric pathology, including reduced infiltration of inflammation and lower incidence of precancerous lesions. RNA-Sequencing results showed that probiotics treatment decreased expressions of genes involved in pro-inflammatory pathways, such as NF-κB, IL-17, and TNF signaling pathway. Of note, probiotics did not suppress the growth of H. pylori, but dramatically reshaped the structure of both gastric and gut microbiota. The microbial diversity was increased in H. pylori-infected group after probiotics treatment. While gastric cancer-associated genera Lactobacillus and Staphylococcus were enriched in the stomach of H. pylori-infected group, the beneficial short-chain fatty acids-producing bacteria, including Bacteroides, Alloprevotella, and Oscellibacter, were more abundant in mice treated with probiotics. Additionally, probiotics restored the H. pylori-induced reduction of anti-inflammatory bacterium Faecalibaculum in the gut., Conclusions: Probiotics therapy can protect against H. pylori-associated carcinogenesis probably through remodeling gastrointestinal microbiota, which in turn prevent host cells from malignant transformation., (© 2022 John Wiley & Sons Ltd.)

Background: There is increasing evidence that the eradication of Helicobacter pylori leads to the regression of gastric hyperplastic polyps (GHPs). We performed a systematic review with a meta-analysis of randomized controlled trials and observational studies that assessed the effects of eradication., Materials and Methods: We searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies with a combination of the terms "Helicobacter pylori" and "polyps." The risk ratio was used to compare the effect of H. pylori eradication/treatment on GHP. We also calculated the pooled disappearance rate of GHP in the H. pylori eradication/treatment group and persistent infection group., Results: We analyzed data from 6 studies, including 3 RCTs. A total of 58/394 patients were included in the H. pylori treatment/successful eradication group, and 57/302 patients were included in the H. pylori untreated/persistent infection group. The pooled rate of GHP elimination after H. pylori treatment/successful eradication was 59% (95% CI, 43%-75%)/79% (95% CI, 72%-86%). H. pylori treatment/successful eradication significantly increased the GHP elimination rate [ITT: (pooled rate: 58% vs. 0%, RR =22.24, 95% CI, 4.51- 109.78, p = 0.0001), PP: (pooled rate: 65% vs. 0%, RR =22.25, 95% CI, 4.52- 109.37, p = 0.0001)/(pooled rate: 79% vs. 9%, RR =26.87, 95% CI, 1.34-540.5, p = 0.03)]., Conclusions: Our meta-analysis showed that after the eradication of H. pylori, most GHPs are eliminated. Moreover, the treatment/successful eradication of H. pylori increased the GHP elimination rate by more than 20 times that in the control group., (© 2021 John Wiley & Sons Ltd.)

Background: Numerous studies related to Helicobacter pylori (H. pylori) eradication have been published since the discovery of H. pylori. This study aimed to use a quantitative method to assess the development of this field., Materials and Methods: We performed a search of related articles from Web of Science published in 1983-2020 using a combination of the search terms "H. pylori" and "eradication". Eligible studies were included after a two-stage screening process, and the following data were extracted: title, author, institution, country, study type, sample size, eradication regimen, publication year, number of citations, journal, and H-index., Results: A total of 1402 studies were finally identified. The results showed that the period from 1994-2003 was the most influential period in this field. Italy and the USA were dominant countries in this field, while China's publication number increased sharply in the last ten years. Baylor College of Medicine was the most influential institution. Alimentary Pharmacology Therapeutics was the most productive journal. The effects of H. pylori eradication on peptic ulcers and gastric cancer and H. pylori eradication therapy were the most cited topics in this field. After the publish of Maastricht/Florence Ⅳ guideline, the research of quadruple therapy was more than triple therapy. Bismuth-containing quadruple therapy became the most focused regimen after Maastricht/Florence Ⅴ guideline., Conclusions: In this study, we summarized the characteristics of the publications; identified the most influential countries, institutions, journals; identified the popular research topics and eradication regimen of clinical H. pylori eradication., (© 2021 John Wiley & Sons Ltd.)

Emerging evidence suggests that Helicobacter pylori infection is associated with metabolic disorders, although the underlying mechanisms are poorly defined. This study aimed to investigate the interaction among H. pylori, a high-fat diet (HFD), and the gut microbiota with glucose regulation and alterations in microbial metabolites. Mice were randomly allocated to H. pylori-infected and noninfected groups fed a chow diet or an HFD. After 4 weeks, two of the HFD groups were given antibiotic cocktails for 8 weeks to eliminate the gut microbiota. The results showed that an HFD significantly promoted increases in body weight, insulin resistance, and glucose intolerance, which were alleviated to normal after antibiotic treatment. H. pylori infection aggravated HFD-induced hyperglycemia, which could not be restored by antibiotics. The perturbation of the gut microbiota was greater in the mice cotreated with H. pylori and an HFD (HFDHp) compared to those administered either H. pylori or an HFD alone, with a loss of diversity, higher abundance of Helicobacter, and lower abundance of Lactobacillus. Furthermore, compared to that of the HFD alone group, the gut microbiota of the HFDHp group was much more susceptible to antibiotic destruction, with extremely lower diversity and dominance of Klebsiella. Fecal metabolome analyses demonstrated that the combination of H. pylori infection and an HFD altered metabolic composition and function, which were linked to glucose dysregulation. H. pylori infection may exacerbate the dysbiosis of the gut microenvironment induced by an HFD, including alterations in the microbiota and metabolites, which weakens the restorative effect of antibiotics and results in the persistence of glucose disorders. KEY POINTS: • The interplay of Hp, HFD, and antibiotics on glucose metabolism was firstly explored. • Hp infection impaired the effect of antibiotics on HFD-induced glucose dysregulation. • Hp infection altered gut microbiota and metabolites which aggravated by HFD.

Helicobacter pylori ( H. pylori ) infection is the strongest known risk factor for the development of gastric cancer. DNA damage response (DDR) and autophagy play key roles in tumorigenic transformation. However, it remains unclear how H. pylori modulate DDR and autophagy in gastric carcinogenesis. Here we report that H. pylori infection promotes DNA damage via suppression of Rad51 expression through inhibition of autophagy and accumulation of p62 in gastric carcinogenesis. We find that H. pylori activated DNA damage pathway in concert with downregulation of repair protein Rad51 in gastric cells, C57BL/6 mice and Mongolian gerbils. In addition, autophagy was increased early and then decreased gradually during the duration of H. pylori infection in vitro in a CagA-dependent manner. Moreover, loss of autophagy led to promotion of DNA damage in H. pylori -infected cells. Furthermore, knockdown of autophagic substrate p62 upregulated Rad51 expression, and p62 promoted Rad51 ubiquitination via the direct interaction of its UBA domain. Finally, H. pylori infection was associated with elevated levels of p62 in gastric intestinal metaplasia and decreased levels of Rad51 in dysplasia compared to their H. pylori- counterparts. Our findings provide a novel mechanism into the linkage of H. pylori infection, autophagy, DNA damage and gastric tumorigenesis.

Background: There is a lack of reports on the awareness of Helicobacter pylori (H pylori) prevention and treatment in the general Chinese population. And whether the knowledge level will affect their action toward screening was unknown. This study aimed to conduct a national survey on the knowledge, attitudes, and practice regarding H pylori infection in Chinese physicians and the public., Methods: This was an Internet-based survey of the general Chinese population and Chinese physicians from different specialties, carried out from January to February 2019. Both surveys (general population's and physicians') included questions to assess the knowledge and attitudes toward H pylori and its action., Results: A total of 3211 people and 546 physicians were enrolled. In the population, the proportion of subjects who answered correctly to all questions about H pylori's infectivity was only 16%, and that for H pylori's harmfulness and that for H pylori preventive measures were 35% and 43.6%, respectively. In general, physicians had a better understanding of H pylori's harmfulness (83.9%) than the other population. The vast majority of the surveyed population (87.0%) and physicians (82.2%) supported a national H pylori screening plan to prevent gastric cancer. The support ratio paralleled with the overall knowledge level. Unexpectedly, gastroenterologists tend to have a relatively low support rate for H pylori screening than non-gastroenterologists (58.2% vs 84.2%, P < .001), which may be related to consideration of heavy medical burden (67.3%)., Conclusions: The general population in China has relatively insufficient awareness of H pylori, which is incompatible with the highly infectious status. More works on health education are needed to improve the knowledge of this gastric pathogen., (© 2020 John Wiley & Sons Ltd.)

Background and Aim: China is a country with high prevalence of Helicobacter pylori (H. pylori) infection, which in turn is closely related to the occurrence of gastric cancer. Therefore, the risks of H. pylori infection and gastric cancer are highly overlapping, and the prevention and treatment of H. pylori infection are necessary to prevent gastric cancer., Methods: Based on evidence-based medicine and the Delphi method, the National Clinical Medical Research Center for Digestive Disease along with the National Early Gastrointestinal Cancer Prevention and Treatment Center Alliance organized dozens of experts in the fields of digestive diseases, H. pylori research, gastric cancer surgery, epidemiology, health economics, and health management to discuss the relationship between H. pylori eradication and prevention and the treatment of gastric cancer., Results: A preliminary consensus on the relationship between H. pylori infection and gastric cancer, H. pylori eradication and gastric cancer prevention, and H. pylori screening and eradication strategy was reached. The consensus further clarified the relationship between H. pylori and gastric cancer and how to formulate future prevention and control strategies for gastric cancer., Conclusions: This consensus could provide guidance on early detection, diagnosis, and treatment of H. pylori to reduce the occurrence of gastric cancer in China., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Helicobacter pylori ( H. pylori ) recurrence remains a significant public health concern. The study aimed to assess H. pylori reinfection rate and identify its risk factors in China. This prospective open cohort, observational study was performed at 18 hospitals across 15 provinces in China. Consecutive patients who received the successful initial eradication during 1 January 2012 and 31 December 2018 were eligible for enrolment. H. pylori recurrence was defined as reinfection that occurred at more than the 12-month interval after successful initial eradication. Surveyed risk factors that might be associated with reinfection were preliminarily estimated by log-rank test and further determined by Cox regression model to calculate the hazard ratio (HR) and 95% confidence interval (CI). A total of 5193 subjects enrolled in the study. The follow-up intervals varied from 6 to 84 months with a general follow-up rate of 67.9%. Annual reinfection rate was 1.5% (95% CI: 1.2-1.8) per person-year. H. pylori reinfection was independently associated with the following five risk factors: minority groups (HR = 4.7, 95% CI: 1.6-13.9), the education at lower levels (HR = 1.7, 95% CI: 1.1-2.6), a family history of gastric cancer (HR = 9.9, 95% CI: 6.6-14.7), and the residence located in Western China (HR = 5.5, 95% CI: 2.6-11.5) following by in Central China (HR = 4.9, 95% CI: 3-8.1) (all P  < 0.05). Reinfection rate of H. pylori in China is relatively low. Patients with specific properties of ethnic groups, education level, family history, or residence location appear to be at higher risk for reinfection.

Background & Aims: Developing countries are making efforts to improve health management. Practice deviating from the guideline means inefficient control. The study aims to investigate the management of Helicobacter pylori (H pylori) infection from a developing country perspective., Methods: An authoritative survey was conducted in 14th (2014) and 17th (2017) Congress of Gastroenterology China, respectively. The Maastricht V/Florence consensus report was invoked as the evaluation criterion., Results: A total of 4182 valid samples were included in this study. Most of the respondents (94%) updated knowledge by lectures. Respondents had a different awareness rate of H pylori-related diseases, ranging from 45% to 95%. Up to 40% of the respondents did not follow the recommendations for the diagnosis. Choice accuracy of eradication regimens and antibiotic combinations was <70%. About 20% of the respondents did not pay attention to the confirmation after the eradication. The situation had been improved in 2017 when compared with that in 2014 (all P < .05). Multivariate logistic regression analysis revealed that influencing factors including nongastroenterologists, bachelor degree and below, the primary professional title, hospital location, and a small proportion of H pylori infection in daily practice related to the deviation of consensus (all P < .05)., Conclusions: Although the management of H pylori infection has been improved in a developing country, there is still a gap between the real-world practices and the consensus. Influencing factors should be taken into account in decision-making, and the corresponding population should be strengthened with precision training during the promotion of the guideline., (© 2019 John Wiley & Sons Ltd.)

Background & Aims: The eradication rate of Helicobacter pylori (H pylori) has decreased largely because of the antibiotic resistance. We aimed to evaluate the effectiveness and safety of furazolidone-containing quadruple regimens for H pylori eradication., Methods: This was an observational study of furazolidone-containing quadruple regimens for H pylori infection in real-world settings. Data sets were collected from the medical records and telephone interviews of patients referred to a specialist clinic for suspected H pylori reinfection from January 1, 2015, to January 1, 2018, at the First Affiliated Hospital of Nanchang University. Main outcome measures were the eradication rate and adverse reactions during medication., Results: Among 584 patients with H pylori infection that met the inclusion criteria, 561 (96.1%) were treated for the first time, 19 (3.3%) had one, and 4 (0.5%) had two or more prior to furazolidone-containing quadruple regimens. The eradication rates for 10-day and 14-day regimens were 93.7% (95% CI: 91.5%-95.9%) vs 98.2% (95% CI: 95.6%-99.3%), respectively (P = 0.098). Adverse drug reactions occurred in 8.2% (48/584) with abdominal discomfort being the most common symptom. Overall adverse events with 10-day regimens were lower than 14-day regimens (6.1% vs 17.4%, P < 0.001). Logistic regression analysis indicated that poor adherence (adjusted odds ratio [AOR] = 46.5, 95% CI: 9.7-222.4) was correlated with failed eradication. Adverse drug reactions during medication were related to smoking and tobacco status, alcohol intake history, regimens combined with tetracycline, and poor adherence (all P < 0.05)., Conclusions: Furazolidone-containing quadruple regimens proved both safe and highly effective in a real-world setting., (© 2019 John Wiley & Sons Ltd.)

Background: The eradication of Helicobacter pylori (H pylori) has been suggested to reduce the risk of gastric cancer, but its impact on the gut microbiota has attracted public attention. This study aimed to investigate the short-term and long-term effects of bismuth quadruple therapy on both gastric and fecal microbiota., Methods: Ten asymptomatic young adults with H pylori-related gastritis were treated with bismuth quadruple therapy for 14 days, and 7 age-matched adults without H pylori infection were enrolled as healthy controls. Both fecal and gastric mucosa samples were collected from H pylori-positive patients at weeks 0, 6, and 26, while fecal samples were collected from healthy controls. The gastric and gut microbiota were analyzed by 16S rRNA gene sequencing., Results: The structure of the gastric microbiota was significantly changed after the eradication of H pylori with increased alpha diversity over time. The relative abundance of H pylori sharply decreased from more than 70% to nearly 0% after treatment, while some beneficial bacteria, such as Lactobacillus and Bifidobacterium, were increased. The microbial diversity of gut microbiota was higher in H pylori-infected patients than in healthy controls, which tended to decrease after eradication. The potentially beneficial gut bacteria Blautia and Lachnoclostridium were enriched at week 26 compared to week 0, while the pathogenic Alistipes were depleted to a level close to that of the healthy controls., Conclusions: Bismuth quadruple therapy for H pylori eradication can restore the diversity of gastric microbiota with enrichment of beneficial bacteria. The composition of gut microbiota after H pylori eradication trends toward healthy status instead of becoming dysbiotic., (© 2019 John Wiley & Sons Ltd.)

Background: Helicobacter pylori (H. pylori) delivers oncoprotein CagA into gastric epithelial cells via the T4SS and drives activation of multiple oncogenic signalling pathways. YAP, a core effector of the Hippo tumour suppressor pathway, is frequently overexpressed in human cancers, suggesting its potential tumor-promoting role. Although CagA is a casual factor in H. pylori induced gastric carcinogenesis, the link between CagA and YAP pathway has not been identified. In this work, we investigated the regulation of oncogenic YAP pathway by H. pylori CagA., Methods: Expression of YAP and E-cadherin protein in human gastric biopsies were assessed by immunohistochemistry. H. pylori PMSS1 cagA - isogenic mutant strains were generated. Gastric epithelial cells were co-cultured with H. pylori wild-type cagA + strains or isogenic mutants and were also treated by recombinant CagA expression. Immunofluorescence was performed for YAP localization. Immunoblot and quantitative PCR were performed for examining levels of YAP, downstream effectors and markers of epithelial-mesenchymal transition. Verteporfin and siRNA silencing were used to inhibit YAP activity., Results: YAP is significantly upregulated in human gastric carcinogenesis. We generated PMSS1 CagA isogenic mutant strains with chloramphenicol resistance successfully. Our analysis indicated that H. pylori infection induced YAP and downstream effectors in gastric epithelial cells. Importantly, knockout of CagA in 7.13 and PMSS1 strains reduced the expression of YAP by H. pylori infection. Moreover, Inhibition of YAP suppressed H. pylori infection-induced Epithelial-mesenchymal transition (EMT)., Conclusion: Our results indicated that H. pylori CagA as a pathogenic protein promotes oncogenic YAP pathway, which contributes to EMT and gastric tumorigenesis. This study provided a novel mechanistic insight into why cagA + H. pylori infection is associated with a higher risk for the development of gastric cancer.

Background: The efficacy of Helicobacter pylori (H. pylori) eradication has steadily declined, primarily because of antibiotic resistance. This study aimed to evaluate the efficacy and safety of furazolidone eradication therapies as initial treatments for H. pylori infection., Methods: A national, multicenter, open-label, randomized controlled trial was performed at 16 sites across 13 provinces in China to evaluate the efficacy and safety of furazolidone-containing therapies for H. pylori infection. Treatment naïve patients were randomly assigned to: esomeprazole 20 mg, bismuth 220 mg, amoxicillin 1000 mg, and furazolidone 100 mg twice daily for 10 and 7 days (FAB 10 and FAB 7; the same therapy without bismuth (FA 10 and FA 7). The primary and secondary outcomes were the eradication rate and regimen safety, respectively. Treatment success was assessed by the 13 C urea breath test at least 4 weeks after treatment completion., Results: Overall, according to intention-to-treat (ITT) analysis, the eradication rates for FAB 10 and FAB 7 were 86.6% (95% confidence interval [CI], 79.9%-93.2%) and 83.6% (95% CI, 76.3%-90.9%) and for FA 10 and FA 7 were 82.4% (95% CI, 74.9%-89.8%) and 77.6% (95% CI, 69.4%-85.8%), respectively. According to per-protocol analysis, the overall eradication rates for FAB 10 and FAB 7 were 94.7% (95% CI, 90.3%-99.1%) and 90.8% (95% CI, 85.1%-96.5%) and for FA 10 and FA 7 were 90.6% (95% CI, 84.9%-96.3%) and 85.1% (95% CI, 78.2%-92.1%), respectively. The overall prevalence of side effects was 8.1%., Conclusions: Furazolidone-containing therapies, particularly the tested 10-day quadruple therapy, exhibited satisfactory efficacy and safety. This 10-day quadruple therapy represents a promising initial treatment strategy for Chinese patients., (© 2018 John Wiley & Sons Ltd.)

Background: Previous epidemiological studies have suggested a link between Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD), yet animal studies are lacking to elucidate this association. In this study, we evaluated the potential effects of H. pylori infection on NAFLD in mice., Methods: We first established two strains of H. pylori infected mice model with either chow diet or high fat diet (HFD). The body and liver weight, blood glucose, serum transaminases and lipid levels and markers of hepatic inflammation were measured. Histological analyses were also performed on liver tissue. Expressions of fat synthesis genes as well as insulin signaling proteins were also determined., Results: After 24 weeks of treatment, the abdominal circumference, fasting blood glucose, low-density cholesterol and alanine transaminase were significantly increased in HFD feeding mice infected with H. pylori SS1 compared to HFD controls. Moreover, HFD fed mice infected with H. pylori SS1 showed significantly more liver steatosis. H. pylori SS1 infection inhibited phosphorylation of IRS1 and Akt and trended to increase the expression of IL-1β and TNF-α in the liver., Conclusion: H. pylori infection is associated with NAFLD in C57BL/6 mice which depends on the bacterial strain and diet structure. The infection of H. pylori SS1 instead of NCTC11637 in combination with HFD induced more severe liver steatosis. H. pylori infection may play a role in NAFLD development and further studies are needed to determine whether H. pylori eradication can improve NAFLD risk., (Copyright © 2018. Published by Elsevier Masson SAS.)

Background: H. pylori infection induces reactive oxygen species- (ROS-) related DNA damage and activates the PI3K/Akt pathway in gastric epithelial cells. N -Acetylcysteine (NAC) is known as an inhibitor of ROS; the role of NAC in H. pylori -related diseases is unclear., Aim: The aim of this study was to evaluate the role of ROS and the protective role of NAC in the pathogenesis of H. pylori -related diseases., Method: An in vitro coculture system and an in vivo Balb/c mouse model of H. pylori -infected gastric epithelial cells were established. The effects of H. pylori infection on DNA damage and ROS were assessed by the comet assay and fluorescent dichlorofluorescein assay. The level of PI3K/Akt pathway-related proteins was evaluated by Western blotting. The protective role of N -acetylcysteine (NAC) was also evaluated with in vitro and in vivo H. pylori infection models., Results: The results revealed that, in vitro and in vivo , H. pylori infection increased the ROS level and induced DNA damage in gastric epithelial cells. NAC treatment effectively reduced the ROS level and inhibited DNA damage in GES-1 cells and the gastric mucosa of Balb/c mice. H. pylori infection induced ROS-mediated PI3K/Akt pathway activation, and NAC treatment inhibited this effect. However, the gastric mucosa pathological score of the NAC-treated group was not significantly different from that of the untreated group. Furthermore, chronic H. pylori infection decreased APE-1 expression in the gastric mucosa of Balb/c mice., Conclusions: An increased ROS level is a critical mechanism in H. pylori pathogenesis, and NAC may be beneficial for the treatment of H. pylori -related gastric diseases linked to oxidative DNA damage.

The development of new nucleotide sequencing techniques and advanced bioinformatics tools has opened the field for studying the diversity and complexity of the gastrointestinal microbiome independent of traditional cultural methods. Owing largely to the gastric acid barrier, the human stomach was long thought to be sterile. The discovery of Helicobacter pylori, the gram-negative bacterium that infects upwards of 50% of the global population, has started a major paradigm shift in our understanding of the stomach as an ecologic niche for bacteria. Recent sequencing analysis of gastric microbiota showed that H. pylori was not alone and the interaction of H. pylori with those microorganisms might play a part in H. pylori-associated diseases such as gastric cancer. In this review, we summarize the available literature about the changes of gastrointestinal microbiota after H. pylori infection in humans and animal models, and discuss the possible underlying mechanisms including the alterations of the gastric environment, the secretion of hormones and the degree of inflammatory response. In general, information regarding the composition and function of gastrointestinal microbiome is still in its infancy, future studies are needed to elucidate whether and to what extent H. pylori infection perturbs the established microbiota. It is assumed that clarifying the role of gastrointestinal communities in H. pylori-associated diseases will provide an opportunity for translational application as a biomarker for the risk of serious H. pylori diseases and perhaps identify specific organisms for therapeutic eradication., (© 2016 John Wiley & Sons Ltd.)

Emerging evidence suggests that Helicobacter pylori infection is associated with insulin resistance (IR) yet the underlying mechanisms are still obscure. The vital role of gut microbiota in triggering IR has been increasingly reported, however, no study has explored the correlation of gut microbiota and H. pylori-associated IR. Using H. pylori-infected mice model fed different diet structures, we demonstrated that H. pylori infection significantly aggravated high-fat diet (HFD)-induced metabolic disorders at the early stage, the extent of which was close to the effect of long-term HFD. Interestingly, we observed dynamic alterations in gut microbiota that were consistent with the changes in the metabolic phenotype induced by H. pylori and HFD. There may be an interaction among H. pylori, diet and gut microbiota, which dysregulates the host metabolic homeostasis, and treatment of H. pylori may be beneficial to the patients with impaired glucose tolerance in addition to diet control., (Copyright © 2016. Published by Elsevier B.V.)

Objectives: We evaluate the efficacy of concomitant therapy for Helicobacter pylori infection and the associated factors that influence it in China, where it has not previously been investigated., Methods: In this prospective study, 374 consecutive patients with H. pylori infection were randomly assigned to 10 day regimens of concomitant therapy with different proton pump inhibitors: esomeprazole (20 mg)/omeprazole (20 mg), amoxicillin (1000 mg), clarithromycin (500 mg) and metronidazole (400 mg). All drugs were administered twice daily. A [(13)C]urea breath test was performed at least 4 weeks after the completion of treatment. Gene polymorphisms and antimicrobial susceptibility were determined., Results: A total of 374 patients with active, uncomplicated duodenal ulcer disease were enrolled in the study (187 cases in each group). The overall eradication rate resulting from concomitant therapy was 90.7% (PP) and 86.1% (ITT) and the eradication rate was significantly higher in the group that received an esomeprazole-based regimen compared with the group that received an omeprazole-based regimen [95.4% versus 86.0%, respectively, P = 0.003 (PP) and 89.8% versus 82.4%, P = 0.036 (ITT), respectively]. Moreover, the omeprazole-based regimen was an independent risk factor for treatment failure (P = 0.039), as were CYP2C19 extensive metabolizer (P = 0.005), clarithromycin (P = 0.000) and metronidazole resistance (P = 0.000). In addition, CYP2C19 polymorphisms and antibiotic resistance had a synergistic effect on eradication rates. The majority of side effects were mild and none was serious., Conclusions: The 10 day concomitant therapy yielded an eradication rate of nearly 90%. Antibiotic resistance, CYP2C19 polymorphisms and their interactions were closely associated with regimen efficacy., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Some studies have suggested an association between Helicobacter pylori infection and the risk of stroke, but the relationship remains controversial. The aim of this study was to obtain a more comprehensive estimate of H. pylori on the risk of stroke by performing a meta-analysis., Methods: A computerized search of PubMed, EMBASE, and the Cochrane library (including CENTRAL) up to February 2014 was performed to identify eligible studies. Prospective studies reported that a multivariate-adjusted estimate for the association between H. pylori and stroke were included. A random-effects model was used to calculate the overall combined risk., Results: Ten prospective observational studies (6 cohort studies, 4 nested case-control, or case-cohort studies within cohort studies) were included in the meta-analysis. The overall combined odds ratio for H. infection and stroke was .96 (95% confidence interval, .78-1.14). Similar results were yielded in patients with cytotoxin-associated gene-A seropositive strains. The combined estimates were robust across sensitivity analyses and had no observed publication bias., Conclusions: In conclusion, our formal meta-analysis indicated no strong association between H. pylori infection and stroke, neither in those with cytotoxin-associated gene-A-positive infection. We believe that future epidemiologic studies of H. pylori and stroke are unlikely to be fruitful., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)