Search Results (924)

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

Rectifying the microbiome perturbed by Eimeria invasion might alleviate the adverse effects of coccidia on broiler growth. This study employed an in vitro fermentation model to investigate the direct, host-independent effects of two probiotics—Lactobacillus rhamnosus (LR) and Bacillus subtilis (BS)—on the cecal microbiome and metabolome perturbed by Eimeria tenella. Four in vitro fermentation treatments consisted of a healthy control (cecal slurry samples from health broilers), an Eimeria-disturbed control (slurry samples from infected broilers), an LR treatment (Eimeria-infected slurry + 3 × 10⁵ of LR cfu/mL), and a BS treatment (Eimeria-disturbed group + 3 × 10⁵ of BS cfu/mL). 16S rRNA sequencing and metabolomic analysis revealed that Eimeria infection resulted in an increase in microbial alpha diversity, promoted opportunistic pathogens, including Helicobacter and Bacteroides, and suppressed commensals like Lactobacillus, concurrently altering 530 intracellular metabolites. Probiotic supplementation partially restored microbial composition. Notably, LR inoculation rectified 107 metabolites across pathways including galactose metabolism and phosphotransferase systems, primarily affecting membrane phospholipid balance. In contrast, BS addition restored only 64 metabolites, largely related to secondary metabolism. The current in vitro study indicates that LR can directly modulate key metabolic disturbances in a dysbiotic microbiota, while the BS may be more dependent on host-mediated interactions. 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

Background/Objectives: Helicobacter pylori infection remains a significant health concern, as increasing antimicrobial resistance compromises the efficacy of eradication. Understanding regional antimicrobial resistance profiles is crucial for optimizing eradication strategies. In this study, we aimed to evaluate the antimicrobial susceptibility patterns and identify the factors influencing H. pylori culture success. Methods: In this prospective study, 697 gastric tissue samples were collected from consecutive patients who underwent upper endoscopy between November 2023 and May 2025. Tissue samples obtained by forceps biopsy or recovered from rapid urease test kits were cultured for H. pylori. Antimicrobial susceptibility testing was performed using the agar dilution method; factors associated with successful culture were analyzed using logistic regression. Results: Among 488 patients with H. pylori infection, culture and antimicrobial susceptibility testing were successful in 387 (79.3%). The overall antimicrobial resistance rates were 17.8%, 27.1%, 29.5%, 0.3%, and 32.8% for amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin, respectively. Notably, 27.6% (107/387) of the isolates were resistant to two or more antibiotics. Using multivariate analysis, the use of fresh biopsy tissue (odds ratio [OR]: 1.646, 95% confidence interval [CI]: 1.046–2.591, p = 0.031), transport interval (OR: 0.911, 95% CI: 0.853–0.973, p = 0.005), and presence of prior eradication therapy (OR: 0.318, 95% CI: 0.156–0.648, p = 0.002) were identified as significant predictors of culture success. Conclusions: The high rate of clarithromycin resistance underscores the need for susceptibility-guided eradication strategies in this region. Optimizing sample handling, particularly by minimizing transport time and using fresh biopsy tissue, may improve culture yields. Full article

Background and Objectives: There is no universal agreement with regard to the correlation between Helicobacter pylori (H. pylori) infection, type 2 diabetes mellitus (T2DM), and ABO blood group antigens. The data related to these are limited. The purpose of this study is to explore the correlation and frequency of H. pylori infection with T2DM and ABO blood group of adults that reside in Jordan. Materials and Methods: This study adopts a cross-sectional comparison of 149 patients diagnosed with T2DM and 168 non-diabetic controls. The One-Step Immunochromatographic DiaSpot^® test was used to diagnose H. pylori, while standardized hemagglutination through the use of monoclonal anti-A, anti-B, and anti-D reagents was used for ABO blood grouping. Analyses were conducted on the correlation between H. pylori infection, diabetes, and ABO blood group through logistic regression. Results: A total of 89 out of the 317 participants tested positive for H. pylori infection (overall seroprevalence = 28.0%), consisting of 51 of the 149 T2DM patients (34.2%) and 38 (22.6%) of the 168 non-diabetic controls. A significant association was observed between diabetes status and H. pylori infection (χ²(1) = 4.71, p < 0.05), with the probability of being H. pylori-positive 1.78 times higher among diabetics (95% CI: 1.085–2.921). A significant association was found between blood group and H. pylori infection, (χ²(3), n = 317) = 15.01, p < 0.001. Of the 89 H. pylori-positive patients, 21 (23.6%) were in blood group A, 13 (14.6%) in group B, and 44 (49.4%) in group O, with the remaining 11 (12.4%) patients in blood group AB. Conclusions: Significant associations were found between H. pylori infection and both T2DM and blood type. Further longitudinal studies that include larger, more diverse populations and more potentially significant factors are needed to clarify these relationships. Full article

Background and Objectives: Helicobacter pylori (H. pylori) infection remains one of the most common chronic bacterial infections worldwide and is associated with a wide range of gastrointestinal disorders, including gastritis, peptic ulcer disease, and gastric cancer. Increasing rates of antibiotic resistance, particularly to clarithromycin and fluoroquinolones, represent a major therapeutic challenge. The objective of this study was to determine the prevalence of resistance-associated mutations in H. pylori-positive gastric biopsy samples from western Romania. Materials and Methods: We conducted a prospective study from January to December 2024, enrolling 138 patients undergoing gastroscopy. Biopsies were collected from the gastric antrum, and H. pylori infection was confirmed using the rapid urease test (RUT). Positive samples were further analyzed with the GenoType HelicoDR assay to detect mutations in the 23S rRNA gene (clarithromycin resistance) and gyrA gene (fluoroquinolone resistance). Clinical, demographic, and endoscopic data were also collected. Results:H. pylori infection was confirmed in 41.3% of the patients (57), of whom 63.2% (36) were treatment-naïve and 36.8% (21) had prior eradication therapy. Among treatment-naïve patients, clarithromycin resistance was identified in 19.4%, whereas previously treated patients showed a markedly higher resistance rate of 47.6% (p = 0.018). All clarithromycin-resistant cases carried the A2147G (23S MUT3) mutation. Fluoroquinolone resistance was present in 13.9% of naïve patients and increased to 23.8% in those with prior eradication therapy, with resistance linked to gyrA mutations at codons 87 (N87K) and 91 (D91 variants). Combined resistance to both antibiotics was observed only in a subset of previously treated patients. Conclusions: Primary resistance to clarithromycin in western Romania exceeds the 15% threshold defined by international guidelines, making clarithromycin-based triple therapy unsuitable as an empirical first-line option. The findings support the use of bismuth quadruple therapy as the preferred empirical regimen in this region. Also, molecular testing proved effective for rapid identification of resistance-associated mutations. Full article