Search Results (902)

The diagnosis and treatment of Helicobacter pylori infection in children represent a major public health problem worldwide, and although prevalence in developed countries has declined, concern about antibiotic resistance continues to grow. This retrospective study aimed to analyze H. pylori infections in children under 15 years of age in Gipuzkoa (Basque Country, Spain) over a 25-year period and to describe patterns of primary and secondary antimicrobial resistance. All diagnostic tests received at a tertiary referral hospital between 2000 and 2024 were reviewed: urea breath test, gastric biopsy culture, string test, and stool antigen detection. Antimicrobial susceptibility testing was performed using the E-test gradient diffusion method. Out of 2855 children investigated, 26.9 were infected with H. pylori. Eradication control was performed in 62.5% (n = 480) of cases. Antimicrobial susceptibility testing was achieved in 96.5% out of the 400 isolates studied. All isolates were sensitive to amoxicillin and tetracyclines. Primary resistance to clarithromycin, metronidazole, and levofloxacin was 28.9%, 19.4%, and 8.9%, respectively, and secondary resistance was 38.7%, 29.7%, and 5.9%, respectively. H.pylori infection remains a challenge in pediatric patients, and the high resistance observed to clarithromycin and metronidazole makes it necessary to monitor the susceptibility of H.pylori and confirms the need for targeted treatment. Full article

Background: Growing antibiotic resistance and the limited availability of key components in standard Helicobacter pylori treatments have driven the search for effective alternatives. Minocycline, with its broad-spectrum activity and favorable pharmacokinetics, has emerged as a promising substitute. This meta-analysis compares the safety and efficacy of minocycline-containing bismuth quadruple therapy (MBQT) to conventional first-line BQT regimens, incorporating data from the recent study by Lin et al. Methods: The inclusion criteria were randomized controlled trials (RCTs) with a target population of both treatment-naïve and previously treated patients diagnosed with Helicobacter pylori (H. pylori) infection. The intervention received by eligible patients was a minocycline–bismuth quadruple therapy (MBQT) regimen containing bismuth, minocycline, proton pump inhibitors (PPI), and any additional antibiotic with a minimum period of 2 weeks of administration. We excluded study designs other than RCT and clinical trials that include patients without confirmed H. pylori infection, animal populations, in vitro experiments, and reports of other outcomes that did not include a minimum intervention duration of 2 weeks. A comprehensive literature search was conducted on PubMed, EMBASE, Cochrane Library, and ScienceDirect from inception to 20 May 2025. After screening via Rayyan, data were extracted on an Excel spreadsheet. Quality was assessed using the Cochrane RoB 2.0 tool. Eligible randomized controlled trials (RCTs) were included and analyzed using RevMan 5.4. Outcomes assessed were intention-to-treat and per-protocol eradication rates. Adverse effects were compared among therapies. A random-effects model was used; an I² < 50% and p-value < 0.05 indicated homogeneity and significant results respectively. Results: Five RCTs with 7 interventions involving 2812 patients were included. The pooled odds ratio (OR) for MBQT in intention-to-treat (ITT) analysis was 1.25 (95% CI: 0.96–1.61), showing a non-significant trend. No heterogeneity was detected (I² = 0.0%). In the modified ITT (mITT) analysis (2 studies), MBQT showed higher eradication (OR: 1.70, 95% CI: 0.00–1042.90), but wide CI and high heterogeneity (I² = 70.7%) limited interpretation. All studies were included in the per-protocol (PP) analysis, which showed a statistically significant improvement with MBQT (OR: 1.67, 95% CI: 1.14–2.45) and low heterogeneity (I² = 5.2%), suggesting consistent results. Although not statistically significant, MBQT was associated with a slightly lower rate of adverse events compared to standard therapy (OR: 0.81, 95% CI: 0.59–1.12). I² = 50.6% showed moderate heterogeneity in safety outcomes. Discussion: the number of included RCTs was modest, with only five studies meeting eligibility criteria, and only two contributing to the modified intention-to-treat analysis. The risk-of-bias assessment showed variation in methodological quality across the included studies. Several studies exhibited high risk judgments in critical domains. particularly randomization, deviations from intervention, and selective reporting. Patients who completed the treatment benefited more from MBQT, which also had a comparable safety profile to conventional BQT regimens. In the treatment of H. pylori infection, MBQT may be considered a safe alternative for first-line treatment. Full article

The Group-1 carcinogen Helicobacter pylori (H. pylori) secretes the serine protease high-temperature requirement A (HtrA), which is directly involved in the disruption of the epithelial barrier in the stomach. HtrA cleaves the extracellular domains of junctional proteins, including E-cadherin (CDH1), claudin-8, occludin, or desmoglein-2, to open intercellular adhesions, allowing H. pylori to transmigrate to subepithelial regions of the gastric mucosa. In our previous work, we found that Zn²⁺ and Cu²⁺ ions efficiently blocked the HtrA activity. However, the impact of other divalent ions on HtrA activity is rather unknown. In this report, we unexpectedly found a stimulating effect through Mn²⁺, Ni²⁺ and Co²⁺ ions on HtrA oligomerization and activity. In contrast to other tested ions, increasing concentrations of Mn²⁺, Ni²⁺ and Co²⁺ strongly enhanced HtrA multimerization as determined in SDS-PAGE under non-reducing conditions and in casein zymography. Increased proteolytic activity of HtrA was further assessed in in vitro cleavage experiments using casein and CDH1 as substrates. Mechanistically, divalent ions bound to HtrA and induced an active conformation, which strongly increased CDH1 cleavage in vitro. The importance of enhanced HtrA activity was finally underlined by the analysis of CDH1 cleavage in H. pylori infection experiments, showing that Ni²⁺ potentiated HtrA-mediated CDH1 shedding. In summary, this study demonstrates that divalent ions exhibit different effects on HtrA activity and that Ni²⁺ and Co²⁺ enhance proteolytic activity by promoting oligomerization, suggesting that metal availability in the gastric environment affects H. pylori virulence. Full article

Chronic atrophic gastritis (CAG) is a key precursor in the Correa cascade leading to gastric cancer and is driven by long-standing Helicobacter pylori infection, autoimmune reactions, environmental exposures, and persistent inflammation. Emerging evidence indicates that mild to moderate atrophy and part of intestinal metaplasia exhibit a degree of reversibility when etiological eradication, microenvironmental optimization, and regenerative stimulation are achieved. This review summarizes recent advances in the pathological basis, evaluation systems, therapeutic mechanisms, and clinical management strategies of CAG. Reversibility is closely related to residual glandular reserve, stem-cell plasticity, and effective mitigation of chronic inflammation. Current assessment tools integrate OLGA/OLGIM histological staging, high-quality endoscopy with AI assistance, and serological biomarkers. Fundamental interventions include early H. pylori eradication, mucosal protective agents, micronutrients, and small-molecule drugs targeting inflammation, oxidative stress, and epithelial regeneration. Novel strategies such as mesenchymal stem cells, exosomes, and focal endoscopic therapies demonstrate regenerative potential in preclinical studies. Traditional Chinese medicine provides multi-target regulation of inflammation, apoptosis, microecology, and stem-cell-related pathways, contributing to histological improvement. Contemporary guidelines emphasize early eradication, risk-stratified surveillance, and comprehensive intervention. Future directions focus on unified evaluation criteria, long-term prospective studies, multimodal combination regimens, and integration of AI-based risk modeling to achieve precise, cancer-preventive CAG management. Full article

Helicobacter pylori is a prevalent gastric pathogen that establishes chronic infection and contributes to gastritis, peptic ulcer disease, and gastric cancer. Its persistence depends on immune evasion strategies that promote sustained low-grade inflammation in the gastric mucosa. Nucleotide-binding oligomerization domain-like receptors (NLRs) are cytosolic pattern recognition receptors that play key roles in innate immune responses against H. pylori. Nod1 and Nod2 detect bacterial peptidoglycan delivered via the type IV secretion system or outer membrane vesicles, activating NF-κB, MAPK, and interferon signaling pathways that regulate inflammatory cytokine production, epithelial barrier function, autophagy, and antimicrobial defense. The NLRP3 inflammasome mediates the maturation of IL-1β and IL-18 primarily in myeloid cells, thereby shaping inflammatory and immunoregulatory responses during infection. In contrast, NLRC4 functions in a context-dependent manner in epithelial cells and is largely dispensable for myeloid IL-1β production. Emerging evidence also implicates noncanonical NLRs, including NLRP6, NLRP9, NLRP12, NLRX1, and NLRC5, in regulating inflammation, epithelial homeostasis, and gastric tumorigenesis. In addition, genetic polymorphisms in NLR genes influence host susceptibility to H. pylori-associated diseases. This review highlights the interplay between NLR signaling, bacterial virulence, and host immunity and identifies potential therapeutic targets. Full article

Helicobacter pylori (H. pylori) is recognized as one of the most widespread and persistent bacterial infections globally, with a remarkable ability to colonize the human stomach. This pathogen is a major contributor to the development of gastric diseases, including gastric lymphoma and adenocarcinoma. The H. pylori infection triggers a complex pathogenic cascade within the gastric environment, characterized by prolonged inflammation and heightened oxidative stress, which fosters a milieu of immune dysregulation, where both innate and adaptive immune cells become activated inappropriately, thereby leading to epithelial injury and subsequent remodeling of the gastric tissue. As the infection persists, repeated cycles of inflammation and epithelial damage contribute to the development of epigenetic alterations, including changes in DNA methylation, histone modifications, and non-coding RNA expression, all of which render the gastric epithelium more susceptible to further aberrations, including dysplasia and cancer. In this article, we review the latest advances in understanding the molecular mechanisms of H. pylori-induced gastritis and its role in the progression of gastric cancer, offering new perspectives on the complex biology of this infection and its potential therapeutic implications for preventing the development of gastric malignancies. Full article

Background: Survivin is an anti-apoptotic protein highly expressed during embryonic development and, in adults, mainly in the gastrointestinal epithelium. Its levels decrease in human gastric tissue and cultured cells upon exposure to Helicobacter pylori gamma-glutamyl transpeptidase (GGT), though the underlying mechanism remains unclear. Objective: We aimed to investigate the role of cap-independent translation driven by the Survivin 5′ untranslated region (5′UTR) in response to H. pylori infection in vitro. Methodology: Human cell lines (AGS, GES-1, HeLa, HEK293T) were used alongside bicistronic and monocistronic (Firefly/Renilla luciferases) reporter assays to assess short and long variants of the Survivin 5′UTR and HIV-1 internal ribosome entry site (IRES) sequences. Additional methods included in vitro transcription/translation, RT-qPCR, agarose gel electrophoresis, Western blotting, coupled/uncoupled translation assays, and siRNA silencing. Results: The short variant of the Survivin 5′ UTR supported cap-independent translation, like the HIV-1 IRES. Notably, H. pylori infection suppressed this translation in a GGT-dependent manner in gastric cells, and a similar reduction was observed following treatment with ATO, a known prooxidant. Conclusion: The Survivin 5′UTR exhibits cap-independent translation activity that is inhibited by H. pylori in a GGT-dependent manner, likely via oxidative stress. This mechanism helps to explain the downregulation of Survivin during gastric infection and indicates that oxidative stress can negatively affect both cellular and viral IRES-mediated translation. Full article

Early prevention of pathological changes underlying gastric cancer (GC) development is a critical strategy, offering the most effective opportunity to limit malignant progression and improve patient outcomes. We have previously demonstrated that Helicobacter pylori (Hp) (cagA⁺vacA⁺) contributes to GC development by activating gastric fibroblasts toward CAF-like phenotype, eliciting aggressive, cancer stem cells (CSCs)-related malignant transformation of LGR5⁺ normal epithelial cells. A key mediator of these processes appears to be the NF-κB/STAT3 axis. Therefore, our aim was to investigate the protective role of hydrogen sulfide (H₂S) as a potential novel strategy for counteracting Hp-induced fibroblast reprogramming. Human fibroblasts were infected with Hp (cagA+vacA+) for 120 h. The fast-releasing H₂S donor NaHS (50, 100, 200 and 400 µM) was added every 24 h. Activation markers, corresponding signaling pathways, H₂S release and activities of H₂S-metabolizing enzymes were determined. NaHS reduced Hp-induced fibroblast activation and their pro-inflammatory, pro-tumorigenic markers, which was associated with the inhibition of NF-κB/STAT3 axis and Twist expression. Additionally, it modulated sulfur metabolism while preserving sulfur-enzyme homeostasis. NaHS limited Hp adhesion (high doses), reduced reinfection-induced activation and increased sensitivity of Hp to metronidazole. These findings suggest that H₂S signaling may represent a modulatory factor of NF-κB/STAT3-driven inflammatory responses during Hp infection and warrant further investigation. Full article

Immunotherapy, especially immune checkpoint inhibitors (ICIs), has become one of the core therapeutic approaches in cancer in recent years. It demonstrates remarkable efficacy in the treatment of melanoma and lung cancer. Conversely, its use in treating gastric cancer (GC) is not associated with considerable benefits. The high heterogeneity of GC and the tumor microenvironment (TME) may directly influence this phenomenon. This review focuses on the correlation between Helicobacter pylori (H. pylori) infection, gastric physiology, and molecular subtype-specific induction pathways, with emphasis on the unique metabolic features of GC. It explores the connection of H. pylori infection, gastric physiologic functions, and molecular subtype-specific induction mechanism of GC with the special metabolism of GC. It also explains the relationship between immune metabolic reprogramming and the suppressive TME in GC. Crucially, we summarize emerging therapeutic strategies targeting metabolic vulnerabilities. Furthermore, we explore the potential of subtype-guided metabolic therapies to overcome the challenges of the immunosuppressive tumor microenvironment in GC. Full article

Background/Objectives: Although vonoprazan-based triple therapy has improved the first- and second-line Helicobacter pylori eradication rates, a subset of patients still require third-line or later treatments. The present study aimed to evaluate the efficacy and safety of susceptibility-guided eradication strategies from third-line or later treatments in a multicenter setting. Methods: This retrospective multicenter study (2019–2024) enrolled 94 patients who had failed second-line eradication therapy and underwent H. pylori isolation and susceptibility testing. Based on sitafloxacin sensitivity, patients received vonoprazan, amoxicillin, and sitafloxacin (VAS) if sensitive, or vonoprazan, amoxicillin, and rifabutin (VAR) if resistant. Altogether, 75 patients received treatment according to this protocol. Results: Among the 75 patients, 61.3% were sitafloxacin-sensitive (VAS group), and 38.7% were resistant (VAR group). All strains were rifabutin-sensitive. The overall eradication rates were 92.0% and 95.8% in the intention-to-treat and per-protocol analyses, respectively. Adverse events occurred in 17.3% of cases. One patient in the VAR group discontinued therapy due to dizziness, whereas all other adverse events were mild and did not require treatment cessation. Subgroup analysis showed eradication rates of 93.5% (43/46) and 89.7% (26/29) for the VAS and VAR groups, respectively. The eradication rate for third-line therapy was 96.2% (50/52), whereas that for fourth-line therapy was 85.7% (18/21). Fifth-line therapy showed an eradication rate of 50.0% (1/2). Conclusions: Susceptibility-guided vonoprazan-based regimens from the third-line treatment onward achieved high eradication and tolerability in a multicenter cohort. This approach may offer a valuable treatment option for patients with refractory H. pylori infections. Full article

Helicobacter pylori infection is a primary cause of gastritis and gastric ulcers. It is crucial to find alternative therapies for H. pylori infection due to the significant side effects of current antibiotics. Heyndrickxia coagulans is an ideal probiotic due to its functionality and stability in production and storage. This study explored the anti-bacterial effects of H. coagulans BHE26 in vitro and in vivo. H. coagulans BHE26 showed notable tolerance to simulated gastric juice (pH 3.0) and 1% bile salts, highlighting its potential suitability for gastrointestinal survival. H. coagulans BHE26 was resistant to ceftriaxone but sensitive to penicillin, ampicillin, erythromycin, gentamicin, ciprofloxacin, ceftriaxone, lincomycin, tetracycline and chloramphenicol. These characteristics showed that H. coagulans BHE26 is a potential probiotic bacterium. In vitro assays demonstrated that H. coagulans BHE26 inhibited H. pylori, reduced urease activity, and displayed notable auto-aggregation and co-aggregation abilities. In vivo, administration of H. coagulans BHE26 alleviated H. pylori-induced gastric mucosal damage, significantly lowered serum anti-bacterial IgG levels, and modulated gastric microbiota composition, including an increase in Turicibacter and a decrease in Lactobacillus abundance. These results indicate that H. coagulans BHE26 alleviated H. pylori-induced inflammation, offering a novel therapeutic strategy against H. pylori infection. Full article

Magnesium aluminate spinel nanoparticles (MgAl₂O₄-S-NPs) represent a promising class of nanoceramics with potential biomedical applications due to their physicochemical stability and antimicrobial properties. This study aimed to determine the structural characteristics, composition, and biological performance of MgAl₂O₄ spinel nanoparticles that were synthesized via a mechanochemical method. Structural and compositional characterization was performed using X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HR-TEM). Antibacterial activity was evaluated against Helicobacter pylori and Enterococcus faecalis using bacterial viability assays. Structural and morphological analyses confirmed the successful formation of single-phase cubic MgAl₂O₄ with a polyhedral morphology and nanoscale size distribution. Bacterial viability was quantified through optical density measurements following exposure to MgAl₂O₄-S-NPs at different concentrations. The nanoparticles exhibited both bacteriostatic and bactericidal effects, with activity being demonstrated against the tested bacterial strains. Mechanochemically synthesized MgAl₂O₄-S-NPs are promising candidates for biomedical applications, including dental materials, antimicrobial coatings, and infection-control strategies. Overall, the findings highlight the potential of MgAl₂O₄-S-NPs as effective antimicrobial agents that can be produced through an environmentally friendly synthesis route. Full article

Human milk oligosaccharides (HMOs) are the third most abundant solid component in human milk and play crucial roles in shaping the gut microbiome and promoting infant health. Although their functions during infancy are well established, emerging evidence suggests that HMOs exert region-specific effects throughout the gastrointestinal tract, extending their benefits beyond early life. This review summarizes current findings on HMO activity in the oral cavity, stomach, small intestine, and large intestine, focusing on their microbiota-modulating, barrier-enhancing, and immunoregulatory effects. In the oral cavity, HMOs inhibit pathogen adhesion and biofilm formation, maintaining oral homeostasis. In the stomach, fucosylated and sialylated HMOs act as soluble decoy receptors, preventing Helicobacter pylori infection. In the small intestine, HMOs strengthen epithelial integrity, regulate inflammation, and promote nutrient absorption. In the large intestine, they serve as selective prebiotics for beneficial microbes, enhancing short-chain fatty acid production and improving barrier function. Although preclinical and clinical studies demonstrate their safety and efficacy, further research is required to elucidate their mechanisms in adults. Overall, HMOs represent multifunctional bioactive glycans with promising applications for gastrointestinal health across all ages. Full article

Helicobacter pylori is one of the most common human pathogens, infecting up to 50% of the global population. The bacterium colonizes the mucus layer overlying gastric epithelial cells and causes chronic infection, which can lead to peptic ulcers, lymphoma, and gastric cancer. Epidemiological studies showed that regions with poor sanitation have higher prevalence rates of H. pylori, suggesting possible environmental or food-related transmission routes in addition to the well-established person-to-person pathways. This assumption is supported by the detection of H. pylori and/or its DNA in a variety of food. Experimental studies further demonstrate that H. pylori can survive in food with certain properties, such as milk, meat, and vegetables, suggesting that such products may serve as potential reservoirs. However, reliable detection of H. pylori in food remains challenging due to its fastidious nature, the ability to enter a viable but non-culturable state, and methodological limitations. While the presence of bacterial DNA and survival across food matrices make foodborne transmission biologically plausible, direct and conclusive proof that ingestion of contaminated food leads to infection is still lacking. Hence, person-to-person transmission currently remains the most firmly established route of transmission. Taken together, the current findings provide substantial indirect evidence that food, particularly under conditions of poor hygiene, may provide a reservoir or vehicle for H. pylori transmission. However, further research is needed to definitively clarify the role of food in the transmission of H. pylori infection and identify appropriate measures to promote public health. Full article