BACKGROUND & AIMS:Helicobacter pylori infection is the principal cause of peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, and noncardia gastric cancer. The major advances in diagnostics and treatment and eradication success are threatened by rising antimicrobial resistance and concerns about disruption of the normal microbiome. This review summarizes current unresolved issues in H pylori treatment, with a focus on resistance, optimal regimens, ecological impact, and emerging therapies. METHODS:Extensive review of randomized controlled trials, meta-analyses, international consensus guidelines, molecular epidemiology studies, microbiome analyses, and translational research related to H pylori eradication, resistance, microbiome effects, and novel therapies. RESULTS:Global resistance to clarithromycin, metronidazole, and fluoroquinolones significantly undermines the performance of traditionally effective antimicrobial therapies. The corner stone of successful antimicrobial therapy is susceptibility-guided therapy but remains of limited use with H pylori because of lack of infrastructure. Eradication regimens potentially induce substantial alterations in gut and gastric microbiota and expand the antimicrobial resistome. Probiotics and N-acetylcysteine offer at best very modest improvements in eradication and tolerability. Novel and still experimental platforms, including engineered phage therapy, antimicrobial peptides, nanoparticle-delivered urease inhibitors, biofilm-targeting agents, and vaccines show promise. Implementation gaps, persistent use of suboptimal regimens, and global inequities constrain the impact of available therapies. CONCLUSIONS:Optimizing H pylori treatment requires evidence-based regimen selection, precision-guided strategies, antimicrobial stewardship, and equitable access to essential medications. Advances in molecular diagnostics, antimicrobial development, and implementation science are all critical to reducing the global burden of H pylori-associated disease and gastric cancer.

BACKGROUND:The price of vonoprazan in the United States, as with many newly introduced drugs, is currently high. Here, we examined the cost-effectiveness of vonoprazan clarithromycin triple therapy for treatment of Helicobacter pylori in the United States. We compared cure rates and total treatment costs to achieve ≥ 90% cure with either vonoprazan or proton pump inhibitor (PPI) triple therapy. MATERIALS AND METHODS:We simulated a theoretical population and compared 4 scenarios comparing vonoprazan 20 mg twice daily or esomeprazole 40 mg twice daily. These included: (1) empiric vonoprazan versus esomeprazole clarithromycin triple therapy, (2) susceptibility-based vonoprazan versus esomeprazole clarithromycin triple therapy, (3) empiric vonoprazan versus esomeprazole clarithromycin triple therapy with treatment failures receiving bismuth quadruple therapy, and (4) susceptibility-based vonoprazan versus esomeprazole clarithromycin triple therapy with treatment failures receiving bismuth quadruple therapy. The prevalence of clarithromycin resistance was estimated at 30%. Cure rates were based on the H. pylori treatment nomogram and drug costs on U.S. 2025 retail prices (i.e., $50 for PPI and $960 for vonoprazan triple therapy). RESULTS:With 30% resistance, susceptibility-based therapy was the most effective (cure rate 92%). With empiric therapy, the cure rate with vonoprazan was higher than esomeprazole (88% vs. 77%) but overall costs increased 2.4-5.2 times. The cost per 1000 patients receiving vonoprazan was approximately $1000,000 versus $50,000 for esomeprazole. The least expensive, highly effective scenario was empiric esomeprazole triple therapy with treatment failures receiving bismuth quadruple therapy. CONCLUSIONS:Any treatment advantage of vonoprazan over PPI in clarithromycin triple therapy is restricted to those with clarithromycin resistance. Vonoprazan triple therapies cost 2 to 5 times more than a high potency PPI with small gains in cure rates. For susceptible infections, triple therapy using a high potency PPI should be preferred, and the most cost-effective strategy is to reserve vonoprazan for refractory cases.

BACKGROUND & AIMS:Helicobacter pylori screening and eradication is a cost-effective strategy for primary gastric cancer prevention in high-risk populations outside the United States. There is a paucity of population-based H pylori seroprevalence data available in high-risk U.S. groups, particularly data for low-income, uninsured patient populations. METHODS:We used data from a cross-sectional study of a largely underserved, immigrant, and minority patient population. Inclusion criteria included asymptomatic individuals 30-65 years of age without prior H pylori testing or treatment. Consented patients completed a study survey and a blood draw to screen for H pylori using IgG serology. We calculated seroprevalence overall and within subgroups of the study population. RESULTS:Screening for H pylori infection was completed in 1021 individuals. Participants had a mean age of 47.5 years and were 69.9% female, and 88.7% were Hispanic individuals. Overall, 63.9% (95% confidence interval [CI], 60.9%-66.8%) of participants were seropositive for H pylori. H pylori seroprevalence was similar across age groups but was higher among males (69.1%; 95% CI, 63.9%-74.2%) than females (61.6%; 95% CI, 58.1%-65.2%). Seroprevalence of H pylori was highest for Hispanic (65.9%; 95% CI, 62.8%-69.0%) and lowest for non-Hispanic White (45.0%; 95% CI, 23.2%-66.8%) individuals. H pylori seroprevalence was highest among individuals born in Central America (75.1%). Risk for infection was no different between second- and third-generation immigrants. CONCLUSIONS:In this population-based study, almost two-thirds of asymptomatic patients were seropositive for H pylori. Prevalence was over 40% among all subgroups. Screening solely based on race and ethnicity may inadvertently exacerbate disparities by overlooking confounding factors for infection like low socioeconomic status and regional exposures.

BACKGROUND:Helicobacter pylori eradication therapy typically consists of a combination of antibiotics and an antisecretory drug. Probiotics may be added to reduce side effects and possibly improve outcomes. MATERIALS AND METHODS:We conducted a double-blind, randomized trial of pantoprazole plus either Lactobacillus reuteri (Gastrus) (high dose) or a matching placebo to assess the impact on the gut microbiota of H. pylori-positive adults. Fecal samples were collected at baseline and after one and 2 months for shotgun metagenomic sequencing. RESULTS:A total of 26 patients were recruited and completed therapy. L. reuteri was only detected in the group that received supplemental L. reuteri and only at the 1-month post-treatment interval. L. reuteri failed to colonize for long-term the gut, and challenge with L. reuteri failed to alter alpha-diversity (Shannon index) or beta-diversity (community ordination) metrics at any time point. Machine learning (PLS-DA) analysis identified the presence of L. reuteri as the most distinguishing feature at 1 month. No other taxa showed a significant difference between groups. CONCLUSION:Short-term administration of pantoprazole and L. reuteri had no lasting effects on gut microbial composition. While L. reuteri transiently bloomed during supplementation, the overall gut microbiota showed resilience, returning to baseline shortly after therapy. TRIAL REGISTRATION:Identifier: NCT03404440.

Background: Dairy consumption has been associated with various health outcomes that may be mediated by changes in gut microbiota. Methods: This cross-sectional study investigated the association between the colonic mucosa-associated gut microbiota and the self-reported intake of total dairy, milk, cheese, and yogurt. A total of 97 colonic mucosal biopsies collected from 34 polyp-free individuals were analyzed. Dairy consumption in the past year was assessed using a food frequency questionnaire. The 16S rRNA gene V4 region was amplified and sequenced. Operational taxonomic unit (OTU) classification was performed using the UPARSE and SILVA databases. OTU diversity and relative abundance were compared between lower vs. higher dairy consumption groups. Multivariable negative binomial regression models for panel data were used to estimate the incidence rate ratio and 95% confidence interval for bacterial counts and dairy consumption. False discovery rate-adjusted p values (q value) < 0.05 indicated statistical significance. Results: Higher total dairy and milk consumption and lower cheese consumption were associated with higher alpha microbial diversity (adjusted p values < 0.05). Higher total dairy and milk consumption was also associated with higher relative abundance of Faecalibacterium. Higher milk consumption was associated with higher relative abundance of Akkermansia. Higher total dairy and cheese consumption was associated with lower relative abundance of Bacteroides. Conclusions: Dairy consumption may influence host health by modulating the structure and composition of the colonic adherent gut microbiota.

It has been 40 years since the first discovery of the important human pathogen, Helicobacter pylori (H. pylori). Eradication of the infection continues to pose significant challenges in part because of the global increase in antibiotic resistance. Generally, the "addition" strategy has failed to deliver the desired results for more than a short period and often contributed to the increase in the prevalence of resistant strains. As such, optimization of each component of the treatment strategy has become an increasingly critical focus of research. In this study, we summarized the evolution of H. pylori eradication regimens and the emergence of promising regimens (e.g., high-dose pronto pump inhibitor dual therapy and potassium-competitive acid blocker dual therapy) in clinical practice. Moreover, we conducted an updated meta-analysis incorporating a total of 29 clinical studies regarding potassium-competitive acid blocker dual therapy. Additionally, we also conducted a network meta-analysis regarding the evaluation of first-line regimens for eradicating H. pylori among patients with penicillin allergy. We concluded that the strategy for the first-line treatment of H. pylori infection needs to shift from the traditional "addition" approach to an optimized "subtraction" approach in this era of increasing antibiotic resistance. Dual therapies, particularly those involving vonoprazan and low-dose amoxicillin, have demonstrated both satisfactory eradication rates and patient adherence.

Background and aims: The American Foregut Society (AFS) recently developed an improved grading system of the esophagogastric junction (EGJ). In our study, we aimed to test the interobserver agreement of AFS EGJ classification system using real-time endoscopy.Methods: We conducted a prospective observational study at a single center from 10-2024 to 12-2024. Inclusion criteria were veterans >= 18 years old referred for upper endoscopy for evaluation of GERD. Exclusion criteria included history of foregut surgery, upper aerodigestive cancer or known major disorder of esophageal peristalsis. Baseline sociodemographic and clinical variables were collected. Five endoscopists completed standardized instruction on EGJ assessment before study initiation. Two endoscopists independently scored the EGJ of each patient. Endoscopists were blinded to one another and self-reported Gastroesophageal Reflux Disease Questionnaire (GERDQ) scores. Interobserver agreement among endoscopists was determined by using the kappa statistic with corresponding 95% confidence intervals (CIs) and strength of agreement was categorized according to established definitions for kappa values.Results: 117 patients met inclusion criteria and 70 successfully completed the study. The mean age was 53 and the participants were predominantly male (76%) and white (57%). Mean body mass index was 31 kg/m2 with 35 (50%) reporting GERD symptoms >= 5 years. The AFS grade demonstrated fair overall interobserver agreement (kappa = .371, P <= .001). AFS grade demonstrated a weak correlation with the GERDQ score (rho = .077, P = .578).Conclusion: The AFS EGJ classification demonstrated fair interobserver agreement between endoscopists for patients referred for endoscopy for evaluation of GERD which has implications for widespread implementation.

BACKGROUND:Helicobacter pylori infections are mostly treated empirically (without antibiotic susceptibility testing). Determining eradication rates of different treatment regimens can inform antibiotic resistance. Our aim was to examine eradication rates of empiric H. pylori treatments based on treatment regimen, race/ethnicity and previous treatment status in a multiethnic U.S. POPULATION: MATERIALS AND METHODS:This was a retrospective cross-sectional study of patients with a positive H. pylori test from 7/2021 to 4/2022 at Harris Health (Houston, Texas) who had received treatment and eradication testing within 1 year. We compared eradication rates based on treatment regimen, race/ethnicity, and prior treatment and examined other possible risk factors for treatment failure using logistic regression models. RESULTS:Among 1106 H. pylori-infected patients, 29.2% were male, 80.6% Hispanic, 10.7% black, 2.5% white, and 83.3% were non-U.S. born with a mean age of 50.8 years (standard deviation 12.6). Most patients (57.3%) received bismuth-tetracycline-metronidazole quadruple, 21.2% clarithromycin-metronidazole-amoxicillin quadruple, 15.6% clarithromycin-amoxicillin triple, and 3.9% received clarithromycin-metronidazole triple therapies. Eradication rates were highest for bismuth-tetracycline-metronidazole quadruple (83.8%), clarithromycin-metronidazole-amoxicillin quadruple (80.3%), and clarithromycin-amoxicillin triple therapies (79.2%). In 186 (16.8%) previously treated patients, all empiric regimens achieved < 80% eradication rates. Clarithromycin-amoxicillin triple had high eradication rates (92.9%) in black patients and bismuth quadruple therapy in Asians (95.8%). Compared to bismuth quadruple therapy, clarithromycin-metronidazole triple (adjusted odds ratio [adjOR] 0.31, 95% confidence interval [CI] 0.13-0.73) and levofloxacin-amoxicillin triple (adjOR 0.20, 95% CI 0.05-0.89) regimens were associated with treatment failure, whereas clarithromycin-amoxicillin quadruple and triple therapies were not. CONCLUSIONS:Empiric bismuth quadruple therapy had the highest eradication rate while metronidazole and levofloxacin triple therapies had the lowest. Eradication rates may thus serve as a surrogate clinical endpoint when choosing empiric therapies.

INTRODUCTION:The aim of this study was to compare the efficacy of 14-day vonoprazan high-dose dual, vonoprazan triple, and rabeprazole reverse hybrid therapies for the first-line treatment of Helicobacter pylori infection. METHODS:In the multicenter, randomized, open-label trial, we consecutively recruited adult H. pylori -infected patients from 6 centers in Taiwan. Subjects were randomly assigned (1:1:1) to 14-day vonoprazan high-dose dual, vonoprazan triple, or rabeprazole reverse hybrid therapy. Eradication status was determined by 13 C-urea breath test. The primary outcome was the eradication rate of H. pylori assessed in the intention-to-treat population. RESULTS:Between December 2021 and April 2024, 906 patients were recruited. The eradication rates were 83.8% (253/302) for vonoprazan high-dose dual therapy, 90.1% (272/302) for vonoprazan triple therapy, and 89.1% (271/302) for rabeprazole reverse hybrid therapy in intention-to-treat analysis. Vonoprazan high-dose dual therapy was inferior to both vonoprazan triple (95% confidence interval -11.5% to -1.1%; P = 0.022) and rabeprazole reverse hybrid therapies (95% confidence interval -10.7% to 0.1%; P = 0.031). There were no significant differences in the overall proportions of patients experiencing adverse events among vonoprazan high-dose dual, vonoprazan triple, and rabeprazole reverse hybrid groups (10.3%, 15.2%, and 15.6%, respectively). Body weight ≥60 kg, clarithromycin resistance, and poor drug adherence were independent risk factors predicting eradication failure for the 3 corresponding therapies, with odds ratios of 3.2 (1.3-7.5), 4.8 (1.2-18.9), and 14.8 (2.8-78.8), respectively. DISCUSSION:Vonoprazan triple therapy and rabeprazole reverse hybrid therapy are preferable to vonoprazan dual therapy for the first-line treatment of H. pylori infection.