Pylori Treatment Research Articles

Effect of probiotic supplementation combined with bismuth-containing quadruple therapy on gut microbiota during Helicobacter pylori eradication: a randomized, double-blind, placebo-controlled trial.

Helicobacter pylori (H. pylori) eradication has been reported to affect gut microbiota distribution. This study aimed to evaluate the effect of probiotic supplementation on the gastrointestinal microbiota during eradication and the efficacy of bismuth-containing quadruple therapy. One hundred treatment-naïve H. pylori-positive patients were randomly assigned 1:1 to receive 14-day bismuth-containing quadruple therapy (esomeprazole, bismuth, amoxicillin, and clarithromycin) combined with the probiotic (Bifidobacterium animalism subsp. lactis BLa80) or placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was completed before and after treatment. Stool samples were collected for 16S rRNA gene sequencing at weeks 0, 2, and 10. No significant difference in the eradication rate was observed between the two groups. The incidence of adverse events, especially nausea (p = 0.029), was lower in the probiotic group. After treatment, the GSRS score decreased significantly in the probiotic group (p = 0.039). The gut microbiota underwent considerable changes immediately following eradication treatment, predominantly characterized by an increase in Proteobacteria at the expense of commensal Firmicutes and Bacteroidota, but gradually returned to baseline after eight weeks. By week 10, beneficial genera such as Lachnoclostridium, Parasutterella, Hungatella, and Akkermansia were notably enriched in the probiotic group. Additionally, the correlation networks in the probiotic group were closer to their initial levels at week 10 compared to the placebo group. Disturbances in the gut microbiota following H. pylori treatment appeared to be temporary, and probiotic supplementation could mitigate antibiotic-induced alterations in the gut microbiota. This study also provided evidence supporting the effectiveness of probiotics in alleviating gastrointestinal symptoms.

Opportunities for Helicobacter pylori Eradication beyond Conventional Antibiotics.

Helicobacter pylori (H. pylori) is a bacterium known to be associated with a significant risk of gastric cancer in addition to chronic gastritis, peptic ulcer, and MALT lymphoma. Although only a small percentage of patients infected with H. pylori develop gastric cancer, Gastric cancer causes more than 750,000 deaths worldwide, with 90% of cases being caused by H. pylori. The eradication of this bacterium rests on multiple drug regimens as guided by various consensus. However, the efficacy of empirical therapy is decreasing due to antimicrobial resistance. In addition, biofilm formation complicates eradication. As the search for new antibiotics lags behind the bacterium's ability to mutate, studies have been directed toward finding new anti-H. pylori agents while also optimizing current drug functions. Targeting biofilm, repurposing outer membrane vesicles that were initially a virulence factor of the bacteria, phage therapy, probiotics, and the construction of nanoparticles might be able to complement or even be alternatives for H. pylori treatment. This review aims to present reports on various compounds, either new or combined with current antibiotics, and their pathways to counteract H. pylori resistance.

The efficacy of keverprazan-based quadruple therapy for Helicobacter pylori eradication: A phase III, randomised, double-blind, multicentre trial

IntroductionKeverprazan is a novel potassium-competitive acid blocker. The advantages of keverprazan as a potent acid suppressor in Helicobacter pylori eradication have not yet been demonstrated. The aim of this study was to evaluate the efficacy of keverprazan as a component of bismuth quadruple therapy in H. pylori treatment. MethodsAdult patients with H. pylori infection were enrolled and randomised to take keverprazan (KEV group)- or esomeprazole (ESO group)-quadruple therapy. The regimens contained keverprazan 20 mg or esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 240 mg and were administered twice daily for 14 days. The primary endpoint was the H. pylori eradication rate at 4 weeks after treatment. ResultsThe full analysis set showed that the H. pylori eradication rates were 87.8% (252/287) and 82.52% (236/286) for the KEV and ESO groups, respectively (difference: 5.29%; 95% confidence interval [CI]: -0.55–11.18). Keverprazan was superior to esomeprazole in terms of eradication rate in the per protocol set (P=0.0382). The eradication rates for patients resistant or non-resistant to clarithromycin were both numerically higher in the KEV group than the ESO group (83.45% vs. 76.98% for clarithromycin-resistance; 92.31% vs. 88.16% for clarithromycin-non-resistance). The incidence of adverse events was similar in the KEV and ESO groups (76.31% vs. 77.62%), with most adverse events (>90%) being mild in severity. No TEAEs led to death in either group. ConclusionsKeverprazan 20 mg twice daily, used as a component of bismuth quadruple therapy, provided effective H. pylori eradication and was non-inferior to an esomeprazole-based regimen.

Gastric cancer prevention by community eradication of Helicobacter pylori: a cluster-randomized controlled trial.

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .

Assessing Accuracy of ChatGPT on Addressing Helicobacter pylori Infection-Related Questions: A National Survey and Comparative Study.

ChatGPT is a novel and online large-scale language model used as a source providing up-to-date and useful health-related knowledges to patients and clinicians. However, its performance on Helicobacter pylori infection-related questions remain unknown. This study aimed to evaluate the accuracy of ChatGPT's responses on H. pylori-related questions compared with that of gastroenterologists during the same period. Twenty-five H. pylori-related questions from five domains: Indication, Diagnostics, Treatment, Gastric cancer and prevention, and Gut Microbiota were selected based on the Maastricht VI Consensus report. Each question was tested three times with ChatGPT3.5 and ChatGPT4. Two independent H. pylori experts assessed the responses from ChatGPT, with discrepancies resolved by a third reviewer. Simultaneously, a nationwide survey with the same questions was conducted among 1279 gastroenterologists and 154 medical students. The accuracy of responses from ChatGPT3.5 and ChatGPT4 was compared with that of gastroenterologists. Overall, both ChatGPT3.5 and ChatGPT4 demonstrated high accuracy, with median accuracy rates of 92% for each of the three responses, surpassing the accuracy of nationwide gastroenterologists (median: 80%) and equivalent to that of senior gastroenterologists. Compared with ChatGPT3.5, ChatGPT4 provided more concise responses with the same accuracy. ChatGPT3.5 performed well in the Indication, Treatment, and Gut Microbiota domains, whereas ChatGPT4 excelled in Diagnostics, Gastric cancer and prevention, and Gut Microbiota domains. ChatGPT exhibited high accuracy and reproducibility in addressing H. pylori-related questions except the decision for H. pylori treatment, performing at the level of senior gastroenterologists and could serve as an auxiliary information tool for assisting patients and clinicians.

Current and Future Perspectives on the Management of Helicobacter pylori: A Narrative Review.

The prevalence of Helicobacter pylori (H. pylori), a pathogen, has decreased globally in the last decade. To date, the management of H. pylori has focused on a reactive approach, whereby those diagnosed are treated with antimicrobials and acid suppression in combination. This review article provides an overview of the shift in the management of H. pylori from a reactive approach towards a proactive 'screen and treat' approach; the article reflects the current pharmacological landscape for H. pylori treatment by exploring similarities such as the first-line prescription of quadruple therapy in most countries and provides a summary table of the best practice guidance from Europe, Asia, and North America. It explores significant ongoing challenges in management, such as rising antimicrobial resistance rates, and explores a potential 'work smart' approach to antimicrobial susceptibility testing. We explore the role of registry databases in providing data on treatment efficacy and safety and how they can support a strategic approach to H. pylori treatment. We question if such a database's availability, update, and regular audit should serve as a key quality indicator in a population screening programme. Despite a call for vaccination against H. pylori and decades of research, not many have made it to a phase-three clinical trial. We explore the challenges that have complicated the development of such a vaccine, such as the genetic diversity of H. pylori, immunotolerance, and limitations of mouse models in research; we reflect on how these challenges are contributing to a low likelihood of having a vaccine in the short-medium term. Lastly, it explores the heterogeneity in research on probiotics and their role as an adjunct in the management of H. pylori.

Helicobacter pylori: High dose amoxicillin does not improve primary or secondary eradication rates in an Irish cohort

BACKGROUND Helicobacter pylori (H. pylori ) eradication rates have fallen globally, likely in large part due to increasing antibiotic resistance to traditional therapy. In areas of high clarithromycin and metronidazole resistance such as ours, Maastricht VI guidelines suggest high dose amoxicillin dual therapy (HDADT) can be considered, subject to evidence for local efficacy. In this study we assess efficacy of HDADT therapy for H. pylori eradication in an Irish cohort. AIM To assess the efficacy of HDADT therapy for H. pylori eradication in an Irish cohort as both first line, and subsequent therapy for patients diagnosed with H. pylori . METHODS All patients testing positive for H. pylori in a tertiary centre were treated prospectively with HDADT (amoxicillin 1 g tid and esomeprazole 40 mg bid × 14 d) over a period of 8 months. Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy. A delta-over-baseline > 4% was considered positive. Patient demographics and treatment outcomes were recorded, analysed and controlled for basic demographics and prior H. pylori treatment. RESULTS One hundred and ninety-eight patients were identified with H. pylori infection, 10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing. In all 139 were included in the analysis, 55% (n = 76) were female, mean age was 46.6 years. Overall, 93 (67%) of patients were treatment-naïve and 46 (33%) had received at least one previous course of treatment. The groups were statistically similar. Self-reported compliance with HDADT was 97%, mild side-effects occurred in 7%. There were no serious adverse drug reactions. Overall the eradication rate for our cohort was 56% (78/139). Eradication rates were worse for those with previous treatment [43% (20/46) vs 62% (58/93), P = 0.0458, odds ratio = 2.15]. Age and Gender had no effect on eradication status. CONCLUSION Overall eradication rates with HDADT were disappointing. Despite being a simple and possibly better tolerated regime, these results do not support its routine use in a high dual resistance country. Further investigation of other regimens to achieve the > 90% eradication target is needed.

Helicobacter pylori Treatment and Gastric Cancer Risk Among Individuals With High Genetic Risk for Gastric Cancer

Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown. To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk. This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu. H pylori treatment and nutrition supplementation. Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk. Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100 228 participants (mean [SD] age, 53.69 [11.00] years; 57 357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation. The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.

Predicting Helicobacter pylori infection from endoscopic features.

Helicobacter pylori infection, prevalent in more than half of the global population, is associated with various gastrointestinal diseases, including peptic ulcers and gastric cancer. The effectiveness of early diagnosis and treatment in preventing gastric cancer highlights the need for improved diagnostic methods. This study aimed to develop a simple scoring system based on endoscopic findings to predict H. pylori infection. A retrospective analysis was conducted on 1,007 patients who underwent upper gastrointestinal endoscopy at Asan Medical Center from January 2019 to December 2021. Exclusion criteria included prior H. pylori treatment, gastric surgery, or gastric malignancies. Diagnostic techniques included rapid urease and 13C-urea breath tests, H. pylori culture, and assessment of endoscopic features following the Kyoto gastritis classification. A new scoring system based on endoscopic findings including regular arrangement of collecting venules (RAC), nodularity, and diffuse or spotty redness was developed for predicting H. pylori infection, utilizing logistic regression analysis in the development set. The scoring system demonstrated high predictive accuracy for H. pylori infection in the validation set. Scores of 2 and 3 were associated with 96% and 99% infection risk, respectively. Additionally, there was a higher prevalence of diffuse redness and sticky mucus in cases where the initial H. pylori eradication treatment failed. Our scoring system showed potential for improving diagnostic accuracy in H. pylori infection. H. pylori testing should be considered upon spotty redness, diffuse redness, nodularity, and RAC absence on endoscopic findings as determined by the predictive scoring system.

Survey on the Knowledge and the Management of Helicobacter pylori Infection by Italian General Practitioners and Doctors in General Practice Training

The management of gastric Helicobacter pylori (H. pylori) infection represents a significant concern in primary healthcare. This survey evaluates the approaches, attitudes, and knowledge regarding gastric H. pylori infection among Italian general practitioners (GPs) and young doctors undergoing general practice training (ITGPs). The survey enrolled 466 GPs and 70 ITGPs. Among GPs, specialist recommendations and the Maastricht–Florence guidelines were frequently referenced sources, while ITGPs relied more on the Maastricht–Florence guidelines and internet resources. ITGPs demonstrated more proactive approaches than GPs in investigating and treating conditions such as gastric ulcers, atrophic gastritis, and iron-deficiency anemia. However, there was limited attention given to the role of H. pylori treatment in first-degree relatives of gastric cancer patients. The most used diagnostic methods were the urea breath test and fecal test. Triple therapy was the most frequently chosen initial treatment regimen, with quadruple bismuth therapy becoming the primary option after initial treatment failure, followed by quinolone therapy and concomitant therapy. This survey underscores a disparity between real-world practices and the recommendations outlined in current guidelines, indicating a need for improved understanding of H. pylori guidelines among both GPs and ITGPs.

Cutting-edge Nanotechnology Approaches in Peptic Ulcer Therapy

Abstract: The ulcer is a chronic disease that penetrates the gastrointestinal tract and produces a deep lesion. One type of ulcer is peptic ulcer, which leads to the development of a lesion on the lining (mucosa) of the digestive tract. Various drugs are used for the treatment, including antibiotics, but don't provide correct eradication, so for the excellence in therapeutic value and decreasing side effects, nanotechnology is being used. Nanotechnology is a technique that is nowadays used in trend because of its outstanding efficacy and also its effect at both cellular and molecular levels. Based on this technology, nanoparticles are used for the treatment of peptic ulcers. This review focuses on the treatment approaches for peptic ulcers by using nanotechnology. Some nanoparticles used in the treatment of Helicobacter pylori (H. pylori) are metallic nanoparticles, polymeric nanoparticles, targeting nanoparticles, and a new technology arrived is membrane coated nanoparticles, which are very advantageous for H. pylori treatment. The purpose of this review is to overview and gain attention to the limitations in treatment (like antibiotic resistance) and also the new strategies to overcome them and enhance the properties of nanoparticles to produce the anti-bacterial effect. This development helps in the treatment of H. pylori.

Change in Diagnosis of Helicobacter pylori Infection in the Treatment-Failure Era.

Helicobacter pylori (H. pylori) infection is a prevalent global health issue, associated with several gastrointestinal disorders, including gastritis, peptic ulcers, and gastric cancer. The landscape of H. pylori treatment has evolved over the years, with increasing challenges due to antibiotic resistance and treatment failure. Traditional diagnostic methods, such as the urea breath test, stool antigen test, and endoscopy with biopsy, are commonly used in clinical practice. However, the emergence of antibiotic-resistant strains has led to a decline in treatment efficacy, necessitating a re-evaluation of common diagnostic tools. This narrative review aims to explore the possible changes in the diagnostic approach of H. pylori infection in the era of treatment failure. Molecular techniques, including polymerase chain reaction and whole genome sequencing, which have high sensitivity and specificity, allow the detection of genes associated with antibiotic resistance. On the other hand, culture isolation and a phenotypic antibiogram could be used in the diagnostic routine, although H. pylori is a fastidious bacterium. However, new molecular approaches are promising tools for detecting the pathogen and its resistance genes. In this regard, more real-life studies are needed to reveal new diagnostic tools suitable for identifying multidrug-resistant H. pylori strains and for outlining proper treatment.

Evaluating the potency of zoliflodacin against Helicobacter pylori: Invitro activity and conserved GyrB target.

The current standard treatment for Helicobacter pylori infection, which involves a combination of two broad-spectrum antibiotics, faces significant challenges due to its detrimental impact on the gut microbiota and the emergence of drug-resistant strains. This underscores the urgent requirement for the development of novel anti-H. pylori drugs. Zoliflodacin, a novel bacterial gyrase inhibitor, is currently undergoing global phase III clinical trials for treating uncomplicated Neisseria gonorrhoeae. However, there is no available data regarding its activity against H. pylori. We evaluated the invitro activity of zoliflodacin against H. pylori clinical isolates (n = 123) with diverse multidrug resistance. We performed DNA gyrase supercoiling and microscale thermophoresis assays to identify the target of zoliflodacin in H. pylori. We analyzed 2262 H. pylori whole genome sequences to identify Asp424Asn and Lys445Asn mutations in DNA gyrase subunit B (GyrB) that are associated with zoliflodacin resistance. Zoliflodacin exhibits potent activity against all tested isolates, with minimal inhibitory concentration (MIC) values ranging from 0.008 to 1 μg/mL (MIC50: 0.125 μg/mL; MIC90: 0.25 μg/mL). Importantly, there was no evidence of cross-resistance to any of the four first-line antibiotics commonly used against H. pylori. We identified GyrB as the primary target of zoliflodacin, with Asp424Asn or Lys445Asn substitutions conferring resistance. Screening of 2262 available H. pylori genomes for the two mutations revealed only one clinical isolate carrying Asp424Asn substitution. These findings support the potential of zoliflodacin as a promising candidate for H. pylori treatment, warranting further development and evaluation.

Molecular investigation of antimicrobial peptides against Helicobacter pylori proteins using a peptide-protein docking approach

The impact of H. pylori resistance on patient's treatment failure is a major concern. Therefore, the development of novel or alternative therapies for H. pylori is urgently needed. The purpose of this study was to investigate the molecular interactions of various antimicrobial peptides (AMPs) to H. pylori proteins. We performed the peptide-protein molecular docking using HADDOCK 2.4 webserver. Fourteen AMPs were tested for their binding efficacy against four H. pylori proteins. Simulation of the peptide-protein complex was performed using molecular dynamic software package AMBER20. From molecular docking analysis, five peptides (LL-37, Tilapia piscidin 4, napin, snakin-1 and EcAMP1) showed strong binding interactions against H. pylori proteins. The strongest binding affinity was observed in the interactions between Snakin-1 and PBP2, TP4 and type I HopQ and EcAMP1 and type I HopQ with −11.1, −13.6 and −13.8 kcal/mol, respectively. The dynamic simulation was performed for two complexes (snakin1-PBP2 and EcAMP1-HopQ). Results of the dynamics simulation showed that EcAMP1 had stable interaction and binding to type I HopQ protein without significant structural changes. In conclusion, both results of docking and simulation showed that EcAMP1 might be useful as a potential therapeutic agent for H. pylori treatment. This molecular approach provides deep understanding of the interaction insights between AMPs and H. pylori proteins. It paves the way for the development of novel anti-H. pylori using antimicrobial peptides.

Value of serum brain-derived neurotrophic factor and glial fibrillary acidic protein for detecting depression in patients with Helicobacter pylori infection

ObjectiveInfection with helicobacter pylori (H. pylori) is associated with depression, and depression can affect the outcome of H. pylori treatment. This study aimed to evaluate the value of serum brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) for predicting depression in H. pylori-positive patients. MethodA total of 82H. pylori-positive and 82H. pylori-negative patients were recruited for this study. All patients underwent neuropsychological and gastrointestinal assessments and blood sampling. BDNF and GFAP levels were measured in serum. The least absolute shrinkage and selection operator (LASSO) model was used to determine a composite marker. ResultsH. pylori-positive patients showed significantly increased serum GFAP levels and significantly decreased serum BDNF levels compared to H. pylori-negative patients. Among H. pylori-positive patients, serum levels of gastrin 17 (G-17), pepsinogen (PG) I/PGII, BDNF, and GFAP, as well as Gastrointestinal Symptom Rating Scale (GSRS) scores, were significantly correlated with Hamilton Depression Scale (HAMD-24) overall scores and factor scores. Interactions between serum BDNF/GFAP and gastrointestinal serum indices or GSRS scores were significantly associated with HAMD-24 scores in H. pylori-positive patients. The LASSO model indicated that the combination of serum BDNF, GFAP, and G-17 and GSRS scores could identify H. pylori-positive patients with depression with an area under the curve of 0.879. ConclusionCirculating changes in BDNF and GFAP were associated with the occurrence of depression in H. pylori-positive patients. A composite marker including neural and gastrointestinal function-related indices may be of value for identifying depression among H. pylori-positive patients.

Eradication of Helicobacter pylori: a prospective comparative randomized trial of standard versus optimized quadruple therapy.

The treatment of Helicobacter pylori infection remains a challenge. None of the proposed treatment regimens has resulted in a 100% eradication rate. The aim of our study was to compare the rate of H.pylori eradication after standard or dose-optimized amoxicillin quadruple therapy.We conducted a prospective comparative study collating patients naive to any anti-H. pylori treatment and with chronic H. pylori infection documented by histological examination. Patients were randomly assigned to either standard quadruple therapy or optimized quadruple therapy. Eradication control was performed by urea breath test. Eighty-eight eligible patients were included with 44 in each group.There was no significant difference between the eradication rates of Qo-14 and Qs-14 neither in ITT (84 vs 70.4%; p=0.127) nor in PP (82.1 vs 77.7%; p=0.473). Compliance and tolerance appeared similar in each group.

Sustained exposure to Helicobacter pylori induces immune tolerance by desensitizing TLR6.

Helicobacter pylori (H. pylori, Hp) has been designated a class I carcinogen and is closely associated with severe gastric diseases. During colonization in the gastric mucosa, H. pylori develops immune escape by inducing host immune tolerance. The gastric epithelium acts as the first line of defense against H. pylori, with Toll-like receptors (TLRs) in gastric epithelial cells being sensitive to H. pylori components and subsequently activating the innate immune system. However, the mechanism of immune tolerance induced by H. pylori through the TLR signalling pathway has not been fully elucidated. In this research, we detected the expression of TLRs and inflammatory cytokines in GES-1 cells upon sustained exposure to H. pylori or H. pylori lysate from 1 to 30 generations and in Mongolian gerbils infected with H. pylori for 5 to 90 weeks. We found that the levels of TLR6 and inflammatory cytokines first increased and then dropped during the course of H. pylori treatment in vitro and in vivo. The restoration of TLR6 potentiated the expression of IL-1β and IL-8 in GES-1 cells, which recruited neutrophils and reduced the colonization of H. pylori in the gastric mucosa of gerbils. Mechanistically, we found that persistent infection with H. pylori reduces the sensitivity of TLR6 to bacterial components and regulates the expression of inflammatory cytokines in GES-1 cells through TLR6/JNK signaling. The TLR6 agonist obviously alleviated inflammation in vitro and in vivo. Promising results suggest that TLR6 may be a potential candidate immunotherapy drug for H. pylori infection.

Kaempferia parviflora Extracellular Vesicle Loaded with Clarithromycin for the Treatment of Helicobacter pylori Infection.

Kaempferia parviflora extracellular vesicles (KPEVs) have been reported as promising nanovesicles for drug delivery. This study aimed to load clarithromycin (CLA) into KPEVs (KPEVS-CLA) and determine the physical properties, drug-releasing efficiency, gastric cell uptake, anti-H. pylori activities, and anti-inflammatory responses in comparison with free CLA and KPEVs. The size and surface charge of KPEVs-CLA were evaluated using dynamic light scattering and visualized using a transmission electron microscope. The encapsulation efficiency (EE%), loading capacity (LC%), and drug release of KPEVs-CLA were examined using HPLC. Anti-H. pylori growth and anti-adhesion were evaluated. IL-8 gene expression, NF-κB signaling proteins, and anti-inflammatory profiles were examined using qRT-PCR, Western blotting, and Bio-Plex immunoassay, respectively. Anti-chemotaxis was then examined using a Transwell assay. KPEVs-CLA were intact and showed a negative surface charge similar to that of KPEVs. However, slightly enlarged KPEVs were observed. CLA was successfully loaded into KPEVs with EE of 93.45% ± 2.43%, LC of 9.3% ± 3.02%. CLA release in the PBS and gastric mimic buffer with Fickian diffusion (n ≤ 0.43) according to Korsmeyer-Peppas kinetic model (R2=0.98). KPEVs-CLA was localized in the gastric cells' cytoplasm and perinuclear region. Anti-H. pylori growth and anti-H. pylori adhesion of KPEVs-CLA were compared with those of free CLA with no cytotoxicity to adenocarcinoma gastric cells. KPEVs-CLA significantly reduced IL-8, G-CSF, MIP-1α, and MIP-1β levels. Moreover, KPEVs-CLA showed a superior effect over CLA in reducing G-CSF, MIP-1α, and NF-κB phosphorylation and monocyte chemotactic activities. KPEVs serve as potential carriers of CLA. They exhibited a higher efficiency in inhibiting gastric cell inflammation mediated by H. pylori infection than free CLA. The establishment of KPEVs-CLA as a nanodrug delivery model for H. pylori treatment could be applied to other plant extracellular vesicles or loaded with other cancer drugs for gastric cancer treatment.

Boosting the Anti-Helicobacter Efficacy of Azithromycin through Natural Compounds: Insights From InVitro, InVivo, Histopathological, and Molecular Docking Investigations.

Antimicrobial-resistant Helicobacter pylori (H. pylori) poses a significant public health concern, especially given the limited therapeutic options for azithromycin-resistant strains. Hence, there is a necessity for new studies to reconsider the use of azithromycin, which has diminished in effectiveness against numerous strains. Thus, we aimed to augment azithromycin's anti-Helicobacter properties by combining it with curcumin in different formulations, including curcumin in clove oil, curcumin nano-gold emulsion, and curcumin nanoemulsion. The antimicrobial activities of the investigated compounds, both individually and in combination with other anti-Helicobacter drugs, were evaluated. Their antibiofilm and anti-virulence properties were assessed using both phenotypic and genotypic methods, alongside molecular docking studies. Our findings were further validated through mouse protection assays and histopathological analysis. We observed high anti-Helicobacter activities of curcumin, especially curcumin nanoemulsion. A synergistic effect was detected between curcumin nanoemulsion and azithromycin with fraction inhibitory concentration index (FICI) values <0.5. The curcumin nanoemulsion was the most active anti-biofilm and anti-virulence compound among the examined substances. The biofilm-correlated virulence genes (babA and hopQ) and ureA genes were downregulated (fold change <1) post-treatment with curcumin nanoemulsion. On the protein level, the anti-virulence activities of curcumin nanoemulsion were documented based on molecular docking studies. These findings aligned with histopathological scoring of challenge mice, affirming the superior efficacy of curcumin nanoemulsion/azithromycin combination. The anti-Helicobacter activities of all curcumin physical forms pose significant challenges due to their higher minimum inhibitory concentration (MIC) values exceeding the maximum permissible level. However, using curcumin nanoemulsion at sub-MIC levels could enhance the anti-Helicobacter activity of azithromycin and exhibit anti-virulence properties, thereby improving patient outcomes and addressing resistant pathogens. Therefore, more extensive studies are necessary to assess the safety of incorporating curcumin nanoemulsion into H. pylori treatment.

Helicobacter pylori Eradication Treatment in Older Patients.

Helicobacter pylori is the main etiopathogenetic factor of chronic gastritis, peptic ulcer disease and gastric cancer. The world's population is shifting towards older people, who have the highest prevalence of H. pylori. Aging-related peculiarities could have an impact on the treatment of H. pylori and there is still a lack of research data in the older population. The aim of this review was to summarize the findings of the most recent information, publications and studies on the issues relating to H. pylori infection in older patients. H. pylori eradication offers gastrointestinal and extra gastrointestinal benefits in older patients. Based on the main guidelines, H. pylori should be eradicated independent of the patient's age, only reconsidering cases with terminal illness and low life expectancy. Proton pump inhibitors are generally safe and well tolerated. Some antibiotics require dose adjustment only in advanced renal insufficiency and the risk of hepatotoxicity is very low. Special precautions should be taken in patients with polypharmacy and those taking aspirin or non-steroidal anti-inflammatory drugs. In older patients, H. pylori eradication treatment frequently causes only mild and short-term adverse events; however, treatment compliance is usually still very good. H. pylori treatment in older patients does not increase the risk of Clostridium difficile infection. Optimal eradication effectiveness (>90%) is mostly achieved with bismuth- and non-bismuth-based quadruple therapies. Susceptibility-guided treatment of H. pylori can contribute to increasing the effectiveness of eradication regimens in older adults. To achieve optimal H. pylori eradication effectiveness in older patients, the same guidelines, which are applied to adults, also apply to this population: avoiding repetitive treatment prescriptions, choosing quadruple therapies, prescribing longer treatment duration and administering high-dose proton pump inhibitors twice daily.