Rapid diagnosis and precision treatment of Helicobacter pylori infection in clinical settings.

Helicobacter pylori is a gram-negative bacterium that colonizes the stomach of approximately half of the worldwide population, with higher prevalence in densely populated areas like Asia, the Caribbean, Latin America, and Africa. H. pylori infections range from asymptomatic cases to potentially fatal diseases, including peptic ulcers, chronic gastritis, and stomach adenocarcinoma. The management of these conditions has become more difficult due to the rising prevalence of drug-resistant H. pylori infections, which ultimately lead to gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. In 1994, the International Agency for Research on Cancer (IARC) categorized H. pylori as a Group I carcinogen, contributing to approximately 780,000 cancer cases annually. Antibiotic resistance against drugs used to treat H. pylori infections ranges between 15% and 50% worldwide, with Asian countries having exceptionally high rates. This review systematically examines the impacts of H. pylori infection, the increasing prevalence of antibiotic resistance, and the urgent need for accurate diagnosis and precision treatment. The present status of precision treatment strategies and prospective approaches for eradicating infections caused by antibiotic-resistant H. pylori will also be evaluated.

Helicobacter pylori vacA allelic combination, dupA, cagE and cagA genotypes and their associations with gastric diseases among Moroccan population.

The combination of the four regions of vacA with cagA, cagE, dupA genes and cagA-EPIYA motifs, was studied to find the most likely combination that can be used as a disease determinant marker in Moroccan population. A total of 838 H. pylori positive obtained from consenting patients, that were previously analyzed by PCR to characterize vacA-s -m, -i regions, cagE status and cagA 3' region polymorphism, were used to characterize vacA-d region and to determine dupA gene status. The analysis shows the predominance of the less virulent combination (vacA(s2m2i2d2)dupA(-)cagE(-)cagA(-)), and shows that the risk of gastric cancer is 13.33 fold higher (1.06-166.37)) in patients infected by strains harboring vacA(s1m1i1d1)dupA(-)cagE(+)cagA(2EPIYA-C) compared to patients with gastritis without lesions and infected by H.pylori strains harboring vacA(s2m2i2d2)dupA(-)cagE(-)cagA(-). The infection with strains harboring vacA(s1m1i1d1)dupA(+)cagE(+)cagA(1EPIYAC) genotype combination represents a risk factor for gastric ulcer and duodenal ulcer (the Odds Ratio (95% CI) were 16 (1.09-234.24) and 6.54 (1.60-26.69) respectively) compared to patients with gastritis without lesions. These results suggest that the combination of the active form of vacA genotypes, dupA gene status and the number of EPIYA-C motif may be considered helpful markers to discriminate between several gastric diseases.

Alginate Oligosaccharides Protect Gastric Epithelial Cells against Oxidative Stress Damage through Induction of the Nrf2 Pathway.

Gastric diseases represent a significant global public health challenge, characterized by molecular dysregulation in redox homeostasis and heightened oxidative stress. Although prior preclinical studies have demonstrated the cytoprotective antioxidant effects of alginate oligosaccharides (AOSs) through the Nrf2 pathway, whether such mechanisms apply to gastric diseases remains unclear. In this study, we used the GES-1 gastric cell line exposed to hydrogen peroxide (H2O2) as a damage model to investigate the impact of AOS on cell viability and its associated mechanisms. Our results revealed that pre-incubation with AOS for either 4 h or 24 h significantly improved the viability of GES-1 cells exposed to H2O2. In addition, AOS reduced the intracellular ROS levels, activating the Nrf2 signaling pathway, with increased Nrf2 protein and mRNA expression and a significant upregulation of the target genes HO-1 and NQO1. The activation of Nrf2 was correlated with decreased Keap1 protein expression and an increased level of the autophagy protein p62/SQSTM1, suggesting the activation of Nrf2 through a noncanonical pathway. This study suggests that AOS is a potential treatment for protecting gastric epithelial cells from oxidative stress by activating the p62/SQSTM1-Keap1-Nrf2 axis and laying the foundation for future investigations about its specific therapeutic mechanisms.

Diminuição da expressão do microRNA-629 em amostras de câncer gástrico potencializada pelo marcador de virulências do H. pylori, gene cagA / Decreased expression of microrna-629 in gastric cancer samples potentiated by the virulence marker of h. pylori, caga gene

ABSTRACT Background: Helicobacter pylori (H. pylori) is a gram-negative bacterium associated with the etiology of several gastrointestinal tract pathologies, and cagA-positive (cagA+) strains are found in populations with gastric ulcers and precancerous lesions, inducing pro-inflammatory responses. The development of neoplasms is related to microRNA (miRNA) dysregulation, indicating highly expressed miRNA-629. The article aims to correlate the expression level of miRNA-629 with the presence of H. pylori and the pathogenicity marker cagA. Methods: 203 gastric biopsy samples were evaluated from individuals with normal gastric tissue (n=60), gastritis (n=96), and gastric cancer (n=47) of both genders and over 18 years old. The samples were subdivided according to the presence or absence of H. pylori, detected by polymerase chain reaction (PCR). RNA was extracted using a commercial kit and quantified. Complementary DNA (cDNA) was synthesized using commercial kits, and the relative expression was calculated using the 2-ΔΔCt method. Results: Individuals infected with H. pylori are nine times more likely to develop gastric cancer. Cancer patients appeared to have decreased expression of miRNA-629; however, the presence of the bacterium would not influence this reduction. Individuals in the cancer group showed lower miRNA-629 expression when cagA+; however, in the control group, the expression was higher when cagA+. Conclusion: H. pylori is a factor involved in the etiology and progression of gastric diseases. Reduction in miRNA-629 expression in cancer patients occurs independent of the presence of the bacterium, but when the cagA pathogenicity marker is present, it induces changes in the gene expression of the respective miRNA.

RESUMO Contexto: Helicobacter pylori (H. pylori) é uma bactéria gram-negativa associada à etiologia de várias patologias do trato gastrointestinal, e cepas positivas para cagA (cagA+) são encontradas em populações com úlceras gástricas e lesões pré-cancerígenas, induzindo respostas pró-inflamatórias. O desenvolvimento de neoplasias está relacionado à desregulação do microRNA (miRNA), indicando miRNA-629 altamente expresso. O artigo tem como objetivo correlacionar o nível de expressão do miRNA-629 com a presença de H. pylori e o marcador de patogenicidade cagA. Métodos: Foram avaliadas 203 amostras de biópsia gástrica de indivíduos com tecido gástrico normal (n=60), gastrite (n=96) e câncer gástrico (n=47) de ambos os sexos e com mais de 18 anos. As amostras foram subdivididas de acordo com a presença ou ausência de H. pylori, detectado por reação em cadeia da polimerase (PCR). O RNA foi extraído usando um kit comercial e quantificado. O DNA complementar (cDNA) foi sintetizado usando kits comerciais, e a expressão relativa foi calculada usando o método 2-ΔΔCt. Resultados: Indivíduos infectados com H. pylori têm nove vezes mais chances de desenvolver câncer gástrico. Pacientes com câncer parecem ter diminuição da expressão do miRNA-629; no entanto, a presença da bactéria não influenciaria essa redução. Indivíduos no grupo do câncer apresentaram menor expressão do miRNA-629 quando cagA+; no entanto, no grupo controle, a expressão foi maior quando cagA+. Conclusão: H. pylori é um fator envolvido na etiologia e progressão das doenças gástricas. A redução na expressão do miRNA-629 em pacientes com câncer ocorre independentemente da presença da bactéria, mas quando o marcador de patogenicidade cagA está presente, induz mudanças na expressão gênica do respectivo miRNA.

Effect of the switch status of Helicobacter pylori outer inflammatory protein A on gastric diseases.

Helicobacter pylori OipA (Outer Inflammatory Protein A) is an outer membrane protein that takes role in the adherence and colonization to the stomach. oipA gene expression is regulated by the slipped-strand mispairing mechanism through a hypermutable CT dinucleotide repeat motif in the 5΄ region. Alterations in the CT number repeats cause frame-shift mutations to result in phase variation of oipA expression. While a functional "On" status has been recognized as a risk factor for peptic ulcer diseases and gastric cancer in many studies, some controversial findings still exist. To this end, this study compiled the sequence data of oipA from 10 different studies between 2000-2019 and 50 oipA DNA sequences from our own research that examined the relationship between the phase On/Off status of oipA and gastric diseases based on CT repeat number. Overall, we have reached 536 oipA DNA sequences from patients. This large collection of oipA sequences first clarified the absolute conservation of the peptide-pentamer of FWLHA for phase ''On'' status, suggesting this pentamer as a superior marker for the determination of oipA status than counting the number of CT repeats. Combining the sequence and patient data, we have re-analyzed the association between the ''On'' status of oipA and gastric diseases. Our results showed a strong association between oipA ''On'' status and gastric cancer supporting previous findings. We also investigated the AlphaFold2 computed structure of OipA that adopts a beta-barrel fold closely resembling to the autotransporter family of H. pylori. Altogether, this study confirms a strong association between oipA ''On'' statuses and severe gastrointestinal diseases like cancer and provides useful insights into the FWLHA pentamer as an indicator of "On" status of oipA putative autotransporter function rather than CT repeats number.

Unusually high clarithromycin resistance in Mycobacterium abscessus subsp. abscessus isolated from human gastric epithelium.

Mycobacterium abscessus subsp. abscessus is a rapidly growing facultative intracellular pathogen that usually infects human lung and skin epithelium. Recently, we and another group have shown that it also has the potential to colonize human gastric epithelium, but its significance with respect to gastric diseases remains unclear. Although Helicobacter pylori still remains the only definite gastric pathogen, recent studies have shown that M. abscessus subsp. abscessus also has the potential to colonize human gastric epithelium. M. abscessus subsp. abscessus is known to exhibit multidrug resistance and clarithromycin has been used as the drug of choice. We aimed to determine the clarithromycin resistance profile of 117 (74 rough and 43 smooth) gastric M. abscessus subsp. abscessus strains and to detect the point mutations in rrl and erm (41) genes conferring the resistance. Our data showed 79.48% (19 smooth and 74 rough) of M. abscessus subsp. abscessus strains were resistant to clarithromycin (MIC90 ≤ 512 µg/mL), while 20.51% (24 smooth) were susceptible (MIC90 ≤ 8 µg/mL). Nucleotide sequence analysis of the rrl gene with reference strains of M. abscessus subsp. abscessus did not show any mutation that is relevant to the clarithromycin resistance. However, analysis of erm (41) gene showed that M. abscessus subsp. abscessus strains, which were susceptible to clarithromycin had C, C, G, and C at their nucleotide positions 28, 159, 238, and 330, respectively, while the resistant strains showed T, T, A, and A at the same positions. Based on antibiogram and sequence analysis data we recommend further studies involving genomic analysis to identify the other genes involved in high clarithromycin resistance in gastric M. abscessus subsp. abscessus along with the mechanisms involved.

Study of Helicobacter pylori Isolated from a High-Gastric-Cancer-Risk Population: Unveiling the Comprehensive Analysis of Virulence-Associated Genes including Secretion Systems, and Genome-Wide Association Study.

BACKGROUND: The prevalence of gastric cancer in Mongolia, in East Asia, remains the highest in the world. However, most Helicobacter pylori strains in Mongolia have a less virulent Western-type CagA. We aimed to determine how H. pylori genomic variation affected gastric diseases, especially gastric cancer, based on comprehensive genome analysis. METHODS: We identified a set of 274 virulence-associated genes in H. pylori, including virulence factor and outer membrane protein (OMP) genes, the type four secretion system gene cluster, and 13 well-known virulence gene genotypes in 223 H. pylori strains and their associations with gastric cancer and other gastric diseases. We conducted a genome-wide association study on 158 H. pylori strains (15 gastric cancer and 143 non-gastric cancer strains). RESULTS: Out of 274 genes, we found 13 genes were variable depending on disease outcome, especially iron regulating OMP genes. H. pylori strains from Mongolia were divided into two main subgroups: subgroup (Sg1) with high risk and Sg2 with low risk for gastric cancer. The general characteristics of Sg1 strains are that they possess more virulence genotype genes. We found nine non-synonymous single nucleotide polymorphisms in seven genes that are linked with gastric cancer strains. CONCLUSIONS: Highly virulent H. pylori strains may adapt through host-influenced genomic variations, potentially impacting gastric carcinogenesis.

Clinical value of serum pepsinogen in the diagnosis and treatment of gastric diseases.

Pepsinogen, secreted from the gastric mucosa, is the precursor of pepsin. It is categorized as pepsinogen 1 and pepsinogen 2 based on its immunogenicity. The pepsinogen content that can enter the blood circulation through the capillaries of the gastric mucosa is approximately 1% and remains stable all the time. The pepsinogen content in serum will change with the pathological changes of gastric mucosa. Therefore, the level of pepsinogen in serum can play a role in serologic biopsy to reflect the function and morphology of different regions of gastric mucosa and serve as an indicator of gastric disease. This study conducts relevant research on serum pepsinogen 1, pepsinogen 2, and the ratio of pepsinogen 1 to pepsinogen 2, and reviews their important value in clinical diagnosis of Helicobacter pylori infection, gastric ulcer, and even gastric carcinoma, providing ideas for other researchers.

Genotyping of Helicobacter pylori CagA/CagE strains in gastric mucosa and its association with gastric illness.

The aim of this work was associate the presence of the virulence factors of Helicobacter pylori, cagA/cagE, with gastric illness. We found evidence that indicate the contribution of these genotypes with the severity of gastric lesions in patients infected, principally in histological subtypes as atrophic gastritis, and metaplasia.

Gastric microbiota dysbiosis and Helicobacter pylori infection.

Helicobacter pylori (H. pylori) infection is one of the most common causes of gastric disease. The persistent increase in antibiotic resistance worldwide has made H. pylori eradication challenging for clinicians. The stomach is unsterile and characterized by a unique niche. Communication among microorganisms in the stomach results in diverse microbial fitness, population dynamics, and functional capacities, which may be positive, negative, or neutral. Here, we review gastric microecology, its imbalance, and gastric diseases. Moreover, we summarize the relationship between H. pylori and gastric microecology, including non-H. pylori bacteria, fungi, and viruses and the possibility of facilitating H. pylori eradication by gastric microecology modulation, including probiotics, prebiotics, postbiotics, synbiotics, and microbiota transplantation.

Heartburn relief with bicarbonate-rich mineral water: results of the randomised, placebo-controlled phase-III trial STOMACH STILL.

OBJECTIVE: We assessed whether the bicarbonate-rich mineral water Staatl. Fachingen STILL is superior over conventional mineral water in relieving heartburn. DESIGN: Multicentre, double-blind, randomised, placebo-controlled trial STOMACH STILL in adult patients with frequent heartburn episodes since ≥6 months and without moderate/severe reflux oesophagitis. Patients drank 1.5 L/day verum or placebo over the course of the day for 6 weeks. Primary endpoint was the percentage of patients with reduction of ≥5 points in the Reflux Disease Questionnaire (RDQ) score for 'heartburn'. Secondary endpoints included symptom reduction (RDQ), health-related quality of life (HRQOL, Quality of Life in Reflux and Dyspepsia (QOLRAD)), intake of rescue medication and safety/tolerability. RESULTS: Of 148 randomised patients (verum: n=73, placebo: n=75), 143 completed the trial. Responder rates were 84.72% in the verum and 63.51% in the placebo group (p=0.0035, number needed to treat=5). Symptoms improved under verum compared with placebo for the dimension 'heartburn' (p=0.0003) and the RDQ total score (p=0.0050). HRQOL improvements under verum compared with placebo were reported for 3 of 5 QOLRAD domains, that is, 'food/drink problems' (p=0.0125), 'emotional distress' (p=0.0147) and 'vitality' (p=0.0393). Mean intake of rescue medication decreased from 0.73 tablets/day at baseline to 0.47 tablets/day in week 6 in the verum group, whereas in the placebo group it remained constant during the trial. Only three patients had treatment-related adverse events (verum: n=1, placebo: n=2). CONCLUSION: STOMACH STILL is the first controlled clinical trial demonstrating superiority of a mineral water over placebo in relieving heartburn, accompanied by an improved HRQOL. TRIAL REGISTRATION NUMBER: EudraCT 2017-001100-30.

Advanced Sensing Strategies Based on Different Types of Biomarkers toward Early Diagnosis of H. pylori.

Helicobacter pylori (H. pylori) is a bacterium that can colonize human gastric epithelial cells and cause H. pylori infection, closely related to many gastric diseases. Compared with conventional H. pylori detection methods, emerging diagnostic approaches (such as biosensors) have become potentially more effective alternatives due to their high sensitivity, good selectivity and noninvasiveness. This review begins with a brief overview of H. pylori infection, the processes that lead to diseases, and current diagnostic methods. Subsequently, advanced biosensors in different target-based for diagnosing H. pylori infection are focused, including the detection of H. pylori-related nucleic acid, H. pylori-related protein (such as the cytotoxin, urease), and intact H. pylori. In addition, prospects for the development of H. pylori detection methods are also discussed in the end.

A deep learning based framework for the classification of multi- class capsule gastroscope image in gastroenterologic diagnosis.

Purpose: The purpose of this paper is to develop a method to automatic classify capsule gastroscope image into three categories to prevent high-risk factors for carcinogenesis, such as atrophic gastritis (AG). The purpose of this research work is to develop a deep learning framework based on transfer learning to classify capsule gastroscope image into three categories: normal gastroscopic image, chronic erosive gastritis images, and ulcer gastric image. Method: In this research work, we proposed deep learning framework based on transfer learning to classify capsule gastroscope image into three categories: normal gastroscopic image, chronic erosive gastritis images, and ulcer gastric image. We used VGG- 16, ResNet-50, and Inception V3 pre-trained models, fine-tuned them and adjust hyperparameters according to our classification problem. Results: A dataset containing 380 images was collected for each capsule gastroscope image category, and divided into training set and test set in a ratio of 70%, and 30% respectively, and then based on the dataset, three methods, including as VGG- 16, ResNet-50, and Inception v3 are used. We achieved highest accuracy of 94.80% by using VGG- 16 to diagnose and classify capsule gastroscopic images into three categories: normal gastroscopic image, chronic erosive gastritis images, and ulcer gastric image. Our proposed approach classified capsule gastroscope image with respectable specificity and accuracy. Conclusion: The primary technique and industry standard for diagnosing and treating numerous stomach problems is gastroscopy. Capsule gastroscope is a new screening tool for gastric diseases. However, a number of elements, including image quality of capsule endoscopy, the doctors' experience and fatigue, limit its effectiveness. Early identification is necessary for high-risk factors for carcinogenesis, such as atrophic gastritis (AG). Our suggested framework will help prevent incorrect diagnoses brought on by low image quality, individual experience, and inadequate gastroscopy inspection coverage, among other factors. As a result, the suggested approach will raise the standard of gastroscopy. Deep learning has great potential in gastritis image classification for assisting with achieving accurate diagnoses after endoscopic procedures.

Association between the Dietary Inflammatory Index and Gastric Disease Risk: Findings from a Korean Population-Based Cohort Study.

Evidence suggests that diets with high pro-inflammatory potential may play a substantial role in the origin of gastric inflammation. This study aimed to examine the association between the energy-adjusted dietary inflammatory index (E-DIITM) and gastric diseases at baseline and after a mean follow-up of 7.4 years in a Korean population. A total of 144,196 participants from the Korean Genome and Epidemiology Study_Health Examination (KoGES_HEXA) cohort were included. E-DII scores were computed using a validated semi-quantitative food frequency questionnaire. Multivariate logistic regression and Cox proportional hazards regression were used to assess the association between the E-DII and gastric disease risk. In the prospective analysis, the risk of developing gastric disease was significantly increased among individuals in the highest quartile of E-DII compared to those in the lowest quartile (HRquartile4vs1 = 1.22; 95% CI = 1.08-1.38). Prospective analysis also showed an increased risk in the incidence of gastritis (HRquartile4vs1 = 1.19; 95% CI = 1.04-1.37), gastric ulcers (HRquartile4vs1 = 1.47; 95% CI = 1.16-1.85), and gastric and duodenal ulcers (HRquartile4vs1 = 1.46; 95% CI = 1.17-1.81) in the highest E-DII quartile compared to the lowest quartile. In the cross-sectional analysis, the E-DII score was not associated with the risk of gastric disease. Our results suggest that a pro-inflammatory diet, indicated by high E-DII scores, is prospectively associated with an increased risk of gastric diseases. These results highlight the significance of an anti-inflammatory diet in lowering the risk of gastric disease risk in the general population.

Helicobacter pylori infection affects the human gastric microbiome, as revealed by metagenomic sequencing.

Helicobacter pylori infection is a prevalent infectious disease, associated with many gastric diseases, including gastritis, gastric ulcer, and gastric cancer. To reveal the characteristics of the gastric microbiome in patients infected with H. pylori, we performed metagenomic shotgun sequencing of stomach swab samples from 96 patients and then conducted metagenomic association analyses between alterations in the gastric microbiome and H. pylori infection status. The overall composition of the gastric microbiota in H. pylori-infected individuals was distinctly different from the negative controls; H. pylori became the dominant species after colonizing the human stomach and significantly decreased the α-diversity of the gastric community (P < 0.05, Wilcoxon rank-sum test). We also identified 6 HPI-associated microbial species (FDR < 0.05, Wilcoxon rank-sum test): Stenotrophomonas maltophilia, Stenotrophomonas unclassified, Chryseobacterium unclassified, Pedobacter unclassified, Variovorax unclassified, and Pseudomonas stutzeri. Furthermore, 55 gastric microbial pathways were enriched in the H. pylori-positive group, whereas only 2 pathways were more abundant in the H. pylori-negative group: dTDP-L-rhamnose biosynthesis and tetrapyrrole biosynthesis (FDR < 0.05, Wilcoxon rank-sum test). Gastritis was not associated with non-H. pylori species in the stomach (P > 0.05, Wilcoxon rank-sum test). This study revealed alterations in gastric microbial taxa and function associated with HPI in the Chinese population, which provides an insight into gastric microbial interactions and their potential role in the pathological process of gastric diseases.

Helicobacter pylori-Mediated Oxidative Stress and Gastric Diseases: A Review.

Gastric cancer is considered to be a type of gastrointestinal tumor and is mostly accompanied by Helicobacter pylori (HP) infection at the early stage. Hence, the long-term colonization of the gastric mucosa by HP as a causative factor for gastrointestinal diseases cannot be ignored. The virulence factors secreted by the bacterium activate the signaling pathway of oxidative stress and mediate chronic inflammatory response in the host cells. The virulence factors also thwart the antibacterial effect of neutrophils. Subsequently, DNA methylation is induced, which causes continuous cell proliferation and evolution toward low-grade-differentiated gastric cells. This process provides the pathological basis for the occurrence of progressive gastric cancer. Therefore, this review aims to summarize the oxidative stress response triggered by HP in the gastric mucosa and the subsequent signaling pathways. The findings are expected to help in the formulation of new targeted drugs for preventing the occurrence of early gastric cancer and its progression to middle and advanced cancer.