Helicobacter pylori (HP) eradication rates are higher by treated with the potassium-competitive acid blocker vonorasan than with proton pump inhibitors (PPIs). Herein, this study analyzed the clinical efficacy of vonoprazan combined with high-dose amoxicillin for dual therapy in personalized eradication of HP.

This retrospective analysis included 452 patients with type I HP who were assigned to the observation and control groups. Cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) antibodies were detected using the H. pylori antibody typing classification assay kit by Western blot. The control group underwent PPI quadruple therapy (oral administration of esomeprazole, amoxicillin, clarithromycin, and colloidal bismuth subcitrate). The observation group was treated with vonoprazan combined with high-dose amoxicillin orally. The clinical efficacy was evaluated after 14 days of treatment, and adverse reactions during treatment were compared. The eradication rates for different HP types in the two groups were detected using a 13C-urea breath test.

There was no significant difference between the control and observation groups in sex, age, BMI, disease duration, smoking history, or drinking history. The observation group exhibited higher total effective rates and better eradication effects than the control group. The CagA+, VacA+, or CagA+VacA+ type patients showed no statistical difference in the incidence of adverse reactions, but the observation group showed a lower total incidence of adverse reactions than the control group.

Vonoprazan combined with high-dose amoxicillin has better clinical efficacy and eradication effect for patients with CagA+VacA+ HP, along with reduced adverse reactions.

Non-cardia gastric cancer remains a major cause of cancer-related mortality worldwide, despite declining incidence rates in many industrialized countries. The development of intestinal-type gastric cancer occurs through a multistep process in which normal mucosa is sequentially transformed into hyperproliferative epithelium, followed by metaplastic processes leading to carcinogenesis. Chronic infection with Helicobacter pylori is the primary etiological agent that causes chronic inflammation of the gastric mucosa, induces atrophic gastritis, and can lead to intestinal metaplasia and dysplasia. Both intestinal metaplasia and dysplasia are precancerous lesions, in which gastric cancer is more likely to occur. Atrophic gastritis often improves after eradication of Helicobacter pylori; however, the occurrence of intestinal metaplasia has been traditionally regarded as "the point of no return" in the carcinogenesis sequence. Helicobacter pylori eradication heals non-atrophic chronic gastritis, may lead to regression of atrophic gastritis, and reduces the risk of gastric cancer in patients with these conditions. In this article, we discuss the pathogenesis, epigenomics, and reversibility of intestinal metaplasia and briefly touch upon potential treatment strategy.

Gastric intestinal metaplasia no longer appears to be an irreversible precancerous lesion. However, there are still many controversies regarding the improvement of intestinal metaplasia after Helicobacter pylori eradication.

Genetic variability of Helicobacter pylori is associated with various gastrointestinal diseases; however, little is known about interaction with sociodemographic in the development of premalignant lesions in Colombian patients.

An analytical study was conducted including cases (patients with gastric atrophy, intestinal metaplasia, and gastric dysplasia) and controls (patients with nonatrophic gastritis). Sociodemographic information was obtained using a questionnaire. Histopathological diagnosis was performed according to the Sydney System. The cagA and vacA genotypes were established using polymerase chain reaction in paraffin blocks. The effect of each variable on the study outcome (premalignant lesion) is presented as odds ratio (OR) and 95% CI. A p value of <0.05 was considered as statistically significant.

The vacA/s1m1 genotype increases the risk of developing premalignant lesions of the stomach (OR: 3.05, 95% IC: 1.57-5.91, p=0.001). Age and educational level showed a positive interaction with the s1m1 genotype (adjusted OR: 3.68, 95% CI: 1.73-7.82, p=0.001). The cagA genotype was not correlated to the development of premalignant lesions of the stomach (OR: 1.32, 95% CI: 0.90-1.94, p=0.151).

The vacA genotype, age, and educational level are indicators of the risk of developing premalignant lesions of the stomach in the study population. Significance Statement. Genetic variability of H. pylori and sociodemographic information could be used to predict the risk of premalignant lesions in stomach in Colombian population.

Stomach pathologies develop in a complex interaction between the host's genetic background and H. pylori virulent genes. Thus, our study aimed to compare active chronic gastritis (ACG), and intestinal metaplasia (IM) with inactive chronic gastritis (ICG), according to interleukin polymorphisms of IL6-174 G/C, IL8-251 A/T, IL1β-511 C/T, and IL1RN VNTR taking into account patient gender and H. pylori genotypes. Interleukin polymorphisms were determined by RFLP-PCR and H. pylori genotype by PCR. IL6-174 GC and IL8-251 T allele showed a protective effect in women against ACG development and, conversely, IL8-251 polymorphism showed a risk for men. More virulent H. pylori strains were associated with the IL8-251 T allele and IL1β-511 T allele in the AGC, and the vacA m1 allele and cagE gene from H. pylori was associated with the IM. Analysis of the progression of gastric lesions must take into account host variability genetic associated with genes H. pylori due to the relation between the virulent H. pylori genes and more severe gastric lesions, besides the relevance to the gender to IL6-174 and IL8-251 polymorphisms.

Gastric cancer (GC) is one of the most common malignancies causing death worldwide, and Helicobacter pylori is a powerful inducer of precancerous lesions and GC. The oral microbiota is a complex ecosystem and is responsible for maintaining homeostasis, modulating the immune system, and resisting pathogens. It has been proposed that the gastric microbiota of oral origin is involved in the development and progression of GC. Nevertheless, the causal relationship between oral microbiota and GC and the role of H. pylori in this relationship is still controversial. This study was set to review the investigations done on oral microbiota and analyze various lines of evidence regarding the role of oral microbiota in GC, to date. Also, we discussed the interaction and relationship between H. pylori and oral microbiota in GC and the current understanding with regard to the underlying mechanisms of oral microbiota in carcinogenesis. More importantly, detecting the patterns of interaction between the oral cavity microbiota and H. pylori may render new clues for the diagnosis or screening of cancer. Integration of oral microbiota and H. pylori might manifest a potential method for the assessment of GC risk. Hence it needs to be specified the patterns of bacterial transmission from the oral cavity to the stomach and their interaction. Further evidence on the mechanisms underlying the oral microbiota communities and how they trigger GC may contribute to the identification of new prevention methods for GC. We may then modulate the oral microbiota by intervening with oral-gastric bacterial transmission or controlling certain bacteria in the oral cavity.

Based on the antibody typing classification, Helicobacter pylori infection can be divided into type I H. pylori infection and type II H. pylori infection. To observe the effects of different H. pylori infection types on the distribution of histopathological characteristics and the levels of three items of serum gastric function (PG I, PG II, G-17). 1175 cases from October 2018 to February 2020 were collected with ratio 1:2. All patients were performed with 14C-Urea breath test (14C-UBT), H. pylori antibody typing classification, three items of serum gastric function detection, painless gastroscopy, pathological examination, etc. According to H. pylori antibody typing classification, patients were divided into three groups: type I H. pylori infection group, type II H. pylori infection group and control group. Significant difference existed among type I H. pylori infection group, type II H. pylori infection group and control group in inflammation and activity (χ2 = 165.43, 354.88, P all < 0.01). The proportion of three groups in OLGA staging had statistic difference (χ2 = 67.99, P all < 0.01); Compared with type II H. pylori infection group and control group, the level of pepsinogen I, pepsinogen II, gastrin17 in type I H. pylori infection group increased, and PG I/PG II ratio (PG I/PG II ratio, PGR) decreased, which was statistically significant (χ2 = 35.08, 166.24, 134.21, 141.19; P all < 0.01). Type I H. pylori infection worsened the severity of gastric mucosal inflammation and activity. H. pylori infection was prone to induce atrophy of gastric mucosa, while type I H. pylori infection played a key role in promoting the progress of atrophic gastritis and affected the level of serum gastric function. The study indicated that the eradication of H. pylori should be treated individually.

Genetic variants within oncogenic long non-coding RNAs HOTAIR and HOTTIP may affect their gene expression levels, thereby modifying genetic susceptibility to gastric cancer (GC). In a hospital-based study in Ardabil-a very high-risk area in North-West Iran, 600 blood samples from 300 GC patients and 300 healthy controls were recruited for genotyping. Seven HOTAIR (i.e., rs17720428, rs7958904, rs1899663, and rs4759314) and HOTTIP (i.e., rs3807598, rs17501292, and rs1859168) 'tag' single nucleotide polymorphisms (SNPs) were genotyped by the Infinium HTS platform. The rs17720428, rs7958904, and rs1899663 tagSNPs significantly increased GC risk under dominant models by 1.5-, 1.57-, and 1.5-fold, respectively. The G-C-T-A haplotype of HOTAIR tagSNPs increased the risk of GC by 1.31-fold. No significant association was found between HOTTIP SNPs and the risk of GC. HOTAIR and HOTTIP variants were also not associated with any clinicopathologic characteristics. The SNP-SNP interaction of HOTAIR rs17720428/rs7958904 with HOTTIP rs1859168 was associated with an increased risk of GC (rs17720428 TG-rs1859168 CC, OR = 1.76; rs7958904 GC-rs1859168 CC, OR = 1.85; rs7958904 CC-rs1859168 CC, OR = 1.86). Interestingly, the SNP-SNP interaction of HOTAIR rs1899663 with HOTTIP rs1859168 strongly increased the risk of GC (rs1899663 GT-rs1859168 CC, OR = 4.3; rs1899663 TT-rs1859168 CC, OR = 9.37; rs1899663 TT-rs1859168 CA, OR = 6.59). We showed that the HOTAIR rs17720428, rs7958904, and rs1899663 tagSNPs and their interactions with the HOTTIP rs1859168 polymorphism significantly increased the risk of GC. Specifically, novel SNP-SNP interactions between HOTAIR and HOTTIP tagSNPs have a larger impact than individual SNP effects on GC risk, thereby providing us with valuable information to reveal potential biological mechanisms for developing GC.

Helicobacter pylori is known as an important determinant of preneoplastic lesions or gastric cancer (GC) risk. The bacterial genotypes may determine the clinical outcomes. However, the evidence for these associations has varied between and within continents, and the actual effect of each gene and corresponding allelic variants are still debatable. In recent years, two new models have been proposed to predict the risk of GC; the phylogeographic origin of H. pylori strains and a disrupted co-evolution between H. pylori and its human host, which potentially explain the geographic differences in the risk of H. pylori-related cancer. However, these models and earlier ones based on putative virulence factors of the bacterium may not fully justify differences in the incidence of GC, reflecting that new theories should be developed and examined. Notably, the new findings also support the role of ancestry-specific germline alteration in contributing to the ethnic/population differences in cancer risk. Moreover the high and low incidence areas of GC have shown differences in transmission ecology, largely affecting the composition of H. pylori populations. As a new hypothesis, it is proposed that any high-risk population may have its own specific risk loci (or variants) as well as new H. pylori strains with national/maybe regional gene pools that should be considered. The latter is seen in the Americas where the rapid evolution of distinct H. pylori subpopulations has been occurred. It is therefore proposed that the deep sequencing of both H. pylori and its human host is simultaneously performed in GC patients and age-sex-matched controls from high-risk areas. The expression and functional activities of the identified new determinants of GC must then be assessed and matched with human and pathogen ancestry, because some of risk loci are ancestry-specific. In addition, potential study-level covariates and moderator variables (eg physical conditions, life styles, gastric microbiome, etc) linked to causal relationships, and their impact, should be recognized and controlled.

Programmed death-ligand 1 (PD-L1) and ICOS-L (also referred to as B7 homolog 1 and 2, respectively) modulate the immune inflammatory response. The aim of the present study was to examine the expression levels of these inflammatory mediators in two groups of patients with an Helicobacter pylori (H. pylori) infection; patients with and without gastric cancer. The association between bacterial virulence factors, CagA and VacA, was also examined, as well as their correlation with the inflammatory profile. Endoscopy analysis indicated that 18 patients suffered from cancer and 28 patients suffered from other gastric pathologies. PCR and reverse transcription-quantitative PCR were used to analyze gastric biopsies and determine the expression levels of the inflammatory modulators PD-L1 and ICOS-L, transcription factors, cytokines and other genes associated with inflammation and pathogenicity. All 46 patients were determined positive for markers of H. pylori. Patients with stomach cancer had lower levels of ICOS-L (P<0.05) and GATA3 (P<0.01), a negative correlation between CagA and IL-17 (P<0.05), a positive correlation between CagA and IL-10 (P<0.05), a negative correlation between vacA-m1 and retinoid orphan receptor γt (RORγt) (P<0.001), and a positive correlation between RORγt and ICOS-L (P<0.001). The reduced levels of ICOS-L and GATA3 along with the negative correlation between CagA and IL-17, and between vacA-m1 and RORγt were all associated with an increased risk of gastric cancer in the present cohort.

Helicobacter pylori (Hp) infection is related to the pathogenesis of chronic gastric disorders and extragastric diseases. Here, we examined the anorexigenic and anxiogenic effects of Hp vacuolating cytotoxin A (VacA) through activation of hypothalamic urocortin1 (Ucn1). VacA was detected in the hypothalamus after peripheral administration and increased Ucn1 mRNA expression and c-Fos-positive cells in the hypothalamus but not in the nucleus tractus solitarius. c-Fos and Ucn1-double positive cells were detected. CRF1 and CRF2 receptor antagonists suppressed VacA-induced anxiety and anorexia, respectively. VacA activated single paraventricular nucleus neurons and A7r5 cells; this activation was inhibited by phospholipase C (PLC) and protein kinase C (PKC) inhibitors. VacA causes anorexia and anxiety through the intracellular PLC-PKC pathway, migrates across the blood-brain barrier, and activates the Ucn1-CRF receptor axis.

Allelic variation of the virulence genes, vacA and cagA, as the most important virulence associated genes play an important role in the pathogenesis of severe gastrointestinal disease.

The aim of the present study was to identify the diversity of the virulence genes in patients with Gastric Cancer (GC), who were referred to the gastro-endoscopy unit of Imam Khomeini Hospital, Ahvaz Jundishapur University of medical science, Ahvaz, Iran.

Gastric biopsy specimens from 301 patients suspected to gastrointestinal disorders, were analyzed for H. pylori using molecular and phenotypical methods (culture, and biochemical test (catalase, oxidase and urease tests)).

Among 201 PCR positive for H. pylori, using histopathological methods, 22 (10.9%) patients had GC. Presence of vacA gene in our H. pylori strains was 100% (201/201), while the most virulent vacA s1 allele was detected in 82.6% isolates, and the mid region vacA m1 was found in 39.8% isolates. The vacA s1/m1 genotype was the most virulent allelic combination in GC and Peptic Ulcer Disease (PUD) in 68.2% and 50%, respectively. The cagA gene was detected in 66.7% isolates. Among the cagA positive isolates, EPIYA-ABC motif was the most common motif in the GC (66.7%), PUD (55.6%) and Erosive Gastroduodenitis (EG) samples (55.2%), while EPIYA-ABCC was the most common motif (58.7%) in the Non-Ulcer Dyspepsia (NUD) samples. The vacA s1m1/cagA⁺ combination was detected in GC (73.3%) and PUD (51.9%), while vacA s1m2/cagA⁺ presented in the NUD and EG samples in 77.8% and 62.1%, respectively.

In this work, Western type (EPIYA-ABC and ABCC motifs) cagA, vacA s1m1 combinations have been demonstrated as the dominant genotype in the tested Ahvazian H. Pylori strains. Also the participation of cagA gene and vacA s1m1 genotype in development and severity of gastric disorder was well evident. Therefore, infection with H. pylori strain containing the cagA gene or the vacA s1m1 genotypes could be associated with increased risk of GC. This is the first study in our area that reports the high incidence and diversity of allelic combination of cagA and vacA genes in gastroduodenitis patients.

Although the most extensive studies revealed the role of H. pylori VacA and CagA toxins in the development of gastric adenocarcinoma, the magnitude of this association and the correlations of vacA mosaicism and cagA status with cardia gastric adenocarcinoma (CGA) still remain controversial.

We aimed to examine the linkage of H. pylori highly cytotoxic genotypes to CGA in Iranian populations as a model.

A total of 601 Iranian patients were enrolled. Biopsies were cultured, genotyped, and anatomically and histologically classified.

The vacA c1 genotype, but not cagA status, showed a strong association with the risk of both CGA and non-cardia adenocarcinoma (NCGA), whether the controls were non-tumors, as those with either non-atrophic gastritis or peptic ulcerations, (the OR (95%CI) was 14.11 (4.91-40.52) and 9.59 (4.06-22.65), respectively) or those with NAG (the OR (95%CI) was 10.71 (3.49-32.82) and 8.11 (3.26-20.16), respectively). The vacA c1/cagA+ genotype was significantly associated with an increased risk of NCGA, whether the controls were non-tumors or those with NAG; the adjusted risk was 4.706 (1.41-15.67) and 4.85 (1.42-16.51), respectively.

The H. pylori vacA c1 genotype, but not cagA status, might be the first important bacterial biomarker for predicting the cardia adenocarcinoma risk in male patients aged ⩾ 55 in Iran.

Frequency of the Helicobacter pylori vacA gene polymorphism and its association with gastric cancer (GC) was assessed in Ardabil, a very high-risk area in Northwestern Iran. We determined the presence of the H. pylori 16S rDNA gene and the vacA s-, m-, i-, and d-region genotypes in DNA from fresh gastric biopsies. Patients with GC were classified based on both the anatomic site and the histopathologic type of tumor Of 135 patients, including 57 with non-atrophic gastritis (NAG) and 78 with GC, 103 were infected by H. pylori. The vacA i1 and d1 genotypes were significantly linked to an increased risk of GC, where both cardia (CGC) and non-cardia GC (NCGC) patients were entered into the analysis. The adjusted OR was 9.59 for i1 and 4.39 for d1. Furthermore, i1 was significantly linked to an increased risk of the intestinal-type adenocarcinoma (OR = 14.04) and d1 to the risk of the diffuse-type adenocarcinoma (OR = 7.71). The presence of the m1-type of vacA in combination with i1 or d1 further increased the risk of GC. When the analysis was restricted to NCGC, the adjusted OR for i1 and d1, was 37.52 and 7.17, respectively. No significant association was found between genotypes and the risk of GC in the cardia site of the stomach. It is proposed that the new types of H. pylori vacA, i1 and d1, might be important determinants of NCGC risk in Ardabil. The m1, not independently, but in combination might further define the risk of GC. i1and d1 might also predict the risk of the intestinal- and diffuse-type adenocarcinomas, respectively.