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Approximately 36% of the United States (US) population is infected with Helicobacter pylori (HP), a known major risk factor for peptic ulcer disease and gastric cancer. HP eradication reduces the rate of complications; however, the benefits are undermined by rising rates of HP eradication treatment failure. This real-world observational cohort analysis aims to describe HP diagnostic and treatment patterns among insured patients in the US. Using diagnoses, lab results, and treatment patterns, we identified adults (18+) with new diagnoses of HP in the Veradigm Health Insights EHR Database linked to Komodo claims data (1/1/2016-12/31/2019). Patients were required to have ≥ 12 months of data pre-/post-index. We captured patient characteristics, HP-related diagnostic testing, and the use of US guideline-recommended HP eradication regimens. HP eradication rates following first-line eradication treatment were measured among patients with available lab results. Overall, 31.8% of the 60,593 included patients did not receive guideline-recommended treatment. Among the 68.2% (41,340) with first-line treatment, 80.2% received clarithromycin-based triple therapy, and 6.6% received bismuth quadruple therapy. Of the 4569 patients with a repeated course of eradication therapy, 53.4% received the same regimen as their first-line, the majority (90.7%) of whom received two rounds of clarithromycin-based triple therapy. Among the 2455 patients with results of HP non-serology testing following first-line treatment, the 180-day eradication rate was 80.2% overall, with differences based on treatments and demographics. This study highlights gaps between guideline-recommended HP management and real-world patterns, underscoring the need to improve HP testing, treatment, and follow-up practices.

Helicobacter pylori colonizes half of the world's population and is responsible for a significant disease burden by causing gastritis, peptic ulcers, and gastric cancer. The development of host inflammation drives these diseases, but there are still open questions in the field about how H. pylori controls this process. We characterized H. pylori inflammation using an 8-month mouse infection time course and comparison of the wild type (WT) and a previously identified mutant lacking the TlpA chemoreceptor that causes elevated inflammation. Our work shows that H. pylori chronic-stage corpus inflammation undergoes surprising fluctuations, with changes in Th17 and eosinophil numbers. The H. pylori tlpA mutant changed the inflammation temporal characteristics, resulting in different inflammation from the wild type at some time points. tlpA mutants have equivalent total and gland colonization in late-stage infections. During early infection, in contrast, they show elevated gland and total colonization compared to those by WT. Our results suggest the chronic inflammation setting is dynamic and may be influenced by colonization properties of early infection.

BackgroundDetailed understanding of pre-, early and late neoplastic states in gastric cancer helps develop better models of risk of progression to gastric cancers (GCs) and medical treatment to intercept such progression.MethodsWe built a Boolean implication network of gastric cancer and deployed machine learning algorithms to develop predictive models of known pre-neoplastic states, e.g., atrophic gastritis, intestinal metaplasia (IM) and low- to high-grade intestinal neoplasia (L/HGIN), and GC. Our approach exploits the presence of asymmetric Boolean implication relationships that are likely to be invariant across almost all gastric cancer datasets. Invariant asymmetric Boolean implication relationships can decipher fundamental time-series underlying the biological data. Pursuing this method, we developed a healthy mucosa → GC continuum model based on this approach.ResultsOur model performed better against publicly available models for distinguishing healthy versus GC samples. Although not trained on IM and L/HGIN datasets, the model could identify the risk of progression to GC via the metaplasia → dysplasia → neoplasia cascade in patient samples. The model could rank all publicly available mouse models for their ability to best recapitulate the gene expression patterns during human GC initiation and progression.ConclusionsA Boolean implication network enabled the identification of hitherto undefined continuum states during GC initiation. The developed model could now serve as a starting point for rationalizing candidate therapeutic targets to intercept GC progression.

The complement system has long been appreciated for its role in bloodborne infections, but its activities in other places, including the gastrointestinal tract, remain elusive. Here, we report that complement restricts gastric infection by the pathogen Helicobacter pylori. This bacterium colonized complement-deficient mice to higher levels than wild-type counterparts, particularly in the gastric corpus region. H. pylori uses uptake of the host molecule L-lactate to create a complement-resistant state that relies on blocking the deposition of the active complement C4b component on H. pylori's surface. H. pylori mutants unable to achieve this complement-resistant state have a significant mouse colonization defect that is largely corrected by mutational removal of complement. This work highlights a previously unknown role for complement in the stomach, and has revealed an unrecognized mechanism for microbial-derived complement resistance.

BackgroundYoghurt can modify gastrointestinal disease risk, possibly acting on gut microbiota. Our study aimed at exploring the under-investigated association between yoghurt and gastric cancer (GC).MethodsWe pooled data from 16 studies from the Stomach Cancer Pooling (StoP) Project. Total yoghurt intake was derived from food frequency questionnaires. We calculated study-specific odds ratios (ORs) of GC and the corresponding 95% confidence intervals (CIs) for increasing categories of yoghurt consumption using univariate and multivariable unconditional logistic regression models. A two-stage analysis, with a meta-analysis of the pooled adjusted data, was conducted.ResultsThe analysis included 6278 GC cases and 14,181 controls, including 1179 cardia and 3463 non-cardia, 1191 diffuse and 1717 intestinal cases. The overall meta-analysis revealed no association between increasing portions of yoghurt intake (continuous) and GC (OR = 0.98, 95% CI = 0.94-1.02). When restricting to cohort studies, a borderline inverse relationship was found (OR = 0.93, 95% CI = 0.88-0.99). The adjusted and unadjusted OR were 0.92 (95% CI = 0.85-0.99) and 0.78 (95% CI = 0.73-0.84) for any vs. no yoghurt consumption and GC risk. The OR for 1 category of increase in yoghurt intake was 0.96 (95% CI = 0.91-1.02) for cardia, 1.03 (95% CI = 1.00-1.07) for non-cardia, 1.12 (95% CI = 1.07-1.19) for diffuse and 1.02 (95% CI = 0.97-1.06) for intestinal GC. No effect was seen within hospital-based and population-based studies, nor in men or women.ConclusionsWe found no association between yoghurt and GC in the main adjusted models, despite sensitivity analyses suggesting a protective effect. Additional studies should further address this association.

Aim: The main objective of this study is to determine the response to the firstline treatment regimen with triple standard therapy (amoxicillin, clarithromycin, omeprazole), to eradicate Helicobacter pylori in a certain population. The goal is to determine if the proposed regimen in international guidelines services is still a suitable option for patients in a certain region of Costa Rica.Methods: The study took place in San Francisco de Asís Hospital, Grecia, Alajuela, Costa Rica. All patients with a Helicobacter pylori infection that were given first- line treatment with triple therapy (amoxicillin, clarithromycin and omeprazole) for its eradication for 14 days, in the period between February of 2017 and February of 2019, were included in the study. Results: A total of 369 cases were identified. The diagnosis was made with biopsy in 96.4% of patients. Response to first-line treatment was achieved in 90.5% corroborated by fecal antigen in 92.1% of all cases.Conclusions: This study shows that triple therapy with amoxicillin, clarithromycin and omeprazole for 14 days maintains an adequate level of efficacy. However, it must be considered that these results are from a specific area and may not reflect the reality of the entire country., Objetivo: Este estudio tiene como objetivo principal determinar la respuesta al esquema de tratamiento de primera línea con triple terapia estándar (amoxicilina, claritromicina, omeprazol), para erradicación de Helicobacter pylori en una determinada población, para determinar si este esquema propuesto en guías internacionales es aún una opción adecuada para pacientes en una determinada región de Costa Rica.Métodos: Se realizó una búsqueda en el servicio de gastroenterología del Hospital San Francisco de Asís, Grecia, Alajuela, Costa Rica; de todos los pacientes con infección por Helicobacter pylori y que recibieron tratamiento de primera línea con triple terapia (amoxicilina, claritromicina y omeprazol) por 14 días, en el periodo comprendido entre febrero 2017 a febrero 2019, incluyendo para el análisis solamente en los que se contaba con una prueba confirmatoria posterior a tratamiento, ya fuera por antígeno fecal de H. pylori o biopsia convencional.Resultados: Se identificaron un total de 369 casos. El diagnóstico se realizó con biopsiaen el 96,4% de los pacientes. La respuesta al tratamiento de primera línea se alcanzó enun 90.5% corroborada por antígeno fecal en el 92.1% de los casos.Conclusiones: Este estudio muestra que la terapia triple con amoxicilina, claritromicina e Inhibidor de bomba de protones por 14 días mantiene un adecuado nivel de eficacia. Sin embargo, hay que tomar en cuenta que estos datos son únicamente de un área de atracción determinada y puede que no reflejen la realidad de todo el país.

Aim: The main objective of this study is to determine the response to the firstline treatment regimen with triple standard therapy (amoxicillin, clarithromycin, omeprazole), to eradicate Helicobacter pylori in a certain population. The goal is to determine if the proposed regimen in international guidelines services is still a suitable option for patients in a certain region of Costa Rica.Methods: The study took place in San Francisco de Asís Hospital, Grecia, Alajuela, Costa Rica. All patients with a Helicobacter pylori infection that were given first- line treatment with triple therapy (amoxicillin, clarithromycin and omeprazole) for its eradication for 14 days, in the period between February of 2017 and February of 2019, were included in the study. Results: A total of 369 cases were identified. The diagnosis was made with biopsy in 96.4% of patients. Response to first-line treatment was achieved in 90.5% corroborated by fecal antigen in 92.1% of all cases.Conclusions: This study shows that triple therapy with amoxicillin, clarithromycin and omeprazole for 14 days maintains an adequate level of efficacy. However, it must be considered that these results are from a specific area and may not reflect the reality of the entire country., Objetivo: Este estudio tiene como objetivo principal determinar la respuesta al esquema de tratamiento de primera línea con triple terapia estándar (amoxicilina, claritromicina, omeprazol), para erradicación de Helicobacter pylori en una determinada población, para determinar si este esquema propuesto en guías internacionales es aún una opción adecuada para pacientes en una determinada región de Costa Rica.Métodos: Se realizó una búsqueda en el servicio de gastroenterología del Hospital San Francisco de Asís, Grecia, Alajuela, Costa Rica; de todos los pacientes con infección por Helicobacter pylori y que recibieron tratamiento de primera línea con triple terapia (amoxicilina, claritromicina y omeprazol) por 14 días, en el periodo comprendido entre febrero 2017 a febrero 2019, incluyendo para el análisis solamente en los que se contaba con una prueba confirmatoria posterior a tratamiento, ya fuera por antígeno fecal de H. pylori o biopsia convencional.Resultados: Se identificaron un total de 369 casos. El diagnóstico se realizó con biopsiaen el 96,4% de los pacientes. La respuesta al tratamiento de primera línea se alcanzó enun 90.5% corroborada por antígeno fecal en el 92.1% de los casos.Conclusiones: Este estudio muestra que la terapia triple con amoxicilina, claritromicina e Inhibidor de bomba de protones por 14 días mantiene un adecuado nivel de eficacia. Sin embargo, hay que tomar en cuenta que estos datos son únicamente de un área de atracción determinada y puede que no reflejen la realidad de todo el país.

Levodopa is the gold standard for the symptomatic treatment of Parkinson's disease (PD). There are well documented motor and non-motor fluctuations, however, that occur almost inevitably once levodopa is started after a variable period in people with PD. Whilst brain neurodegenerative processes play a part in the pathogenesis of these fluctuations, a range of barriers across the gastrointestinal (GI) tract can alter levodopa pharmacokinetics, ultimately contributing to non-optimal levodopa response and symptoms fluctuations. GI barriers to levodopa transport and absorption include dysphagia, delayed gastric emptying, constipation, Helicobacter pylori infection, small intestinal bacterial overgrowth and gut dysbiosis. In addition, a protein-rich diet and concomitant medication intake can further alter levodopa pharmacokinetics. This can result in unpredictable or sub-optimal levodopa response, 'delayed on' or 'no on' phenomena. In this narrative review, we provided an overview on the plethora of GI obstacles to levodopa transport and absorption in PD and their implications on levodopa pharmacokinetics and development of motor fluctuations. In addition, management strategies to address GI dysfunction in PD are highlighted, including use of non-oral therapies to bypass the GI tract.

BackgroundEvidence from epidemiological studies on the role of tea drinking in gastric cancer risk remains inconsistent. We aimed to investigate and quantify the relationship between tea consumption and gastric cancer in the Stomach cancer Pooling (StoP) Project consortium.MethodsA total of 9438 cases and 20,451 controls from 22 studies worldwide were included. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of gastric cancer for regular versus non-regular tea drinkers were estimated by one and two-stage modelling analyses, including terms for sex, age and the main recognised risk factors for gastric cancer.ResultsCompared to non-regular drinkers, the estimated adjusted pooled OR for regular tea drinkers was 0.91 (95% CI: 0.85-0.97). When the amount of tea consumed was considered, the OR for consumption of 1-2 cups/day was 1.01 (95% CI: 0.94-1.09) and for >3 cups/day was 0.91 (95% CI: 0.80-1.03). Stronger inverse associations emerged among regular drinkers in China and Japan (OR: 0.67, 95% CI: 0.49-0.91) where green tea is consumed, in subjects with H. pylori infection (OR: 0.68, 95% CI: 0.58-0.80), and for gastric cardia cancer (OR: 0.64, 95% CI: 0.49-0.84).ConclusionOur results indicate a weak inverse association between tea consumption and gastric cancer.

The role of the gastric mucosal microbiome in Helicobacter pylori-negative gastric cancer (GC) remains unclear. Therefore, we aimed to characterize the microbial alterations and host inflammatory cytokine responses in H. pylori-negative GC. Gastric mucosal samples were obtained from 137 H. pylori-negative patients with GC (n = 45) and controls (chronic gastritis or intestinal metaplasia, n = 92). We performed 16S rRNA gene sequencing (n = 67), a quantitative reverse transcription-polymerase chain reaction to determine the relative mRNA expression levels of TNF (tumor necrosis factor), IL1B (interleukin 1 beta), IL6 (interleukin 6), CXCL8 (C-X-C motif chemokine ligand 8), IL10 (interleukin 10), IL17A (interleukin 17A), TGFB1 (transforming growth factor beta 1) (n = 113), and the correlation analysis between sequencing and expression data (n = 47). Gastric mucosal microbiota in patients with GC showed reduced diversity and a significantly different composition compared to that of the controls. Lacticaseibacillus was significantly enriched, while Haemophilus and Campylobacter were depleted in the cancer group compared to the control group. These taxa could distinguish the two groups in a random forest algorithm. Moreover, the combined relative abundance of these taxa, a GC microbiome index, significantly correlated with gastric mucosal IL1B expression, which was elevated in the cancer group. Overall, altered gastric mucosal microbiota was found to be associated with increased mucosal IL1B expression in H. pylori-negative GC.

Gastric cancer is the third leading cause of cancer-related deaths, with more than one million new cases and approximately 841,000 deaths annually worldwide. We report a case of a young patient (25 years old) with an aggressive form of gastric cancer. The patient had previously been treated for Helicobacter pylori (H. pylori), which is a main risk factor for developing gastric cancer. Genetic testing showed an E-cadherin (CDH1) germline mutation of unknown significance. After eight cycles of chemotherapy, a positron emission tomography (PET) scan showed disease progression with an enlarging hypermetabolic right adnexal mass suspicious for metastatic disease. Tumor pathology demonstrated invasive and poorly differentiated gastric carcinoma. The analysis of the tumor biopsy indicated the very high expression of a chemokine, C-X-C motif chemokine 5 (CXCL5). The combination of H. pylori infection with an existence of a rare CDH1 mutation could have contributed to this aggressive gastric cancer.

Carbohydrate antigen 19-9 (CA 19-9) is a biological marker used to diagnose and monitor the progression of various cancers. Elevated CA 19-9 has also been sporadically observed in Helicobacter pylori infected patients. Similar to H. pylori, animalhosted non-H. pylori Helicobacter (NHPH) species can induce gastroduodenal lesions in humans. We report the first case of CA 19-9 elevation related to H. suis gastritis and its normalisation after eradication. A CA 19-9 screening prescribed as part of a regular check up by the general practitioner was found elevated in a 68-year-old man presenting chronic dyspeptic symptoms. Medical investigations were negative for presence of neoplasia or biliary obstruction. Upper gastrointestinal endoscopy confirmed the presence of chronic gastritis and H. suis was identified in gastric biopsies. The standard treatment for H. pylori successfully eradicated H. suis with normalisation of CA 19-9 levels. In addition to H. pylori, infection with NHPH species should be considered as an additional cause of elevated CA19-9.

Helicobacter pylori is the major risk factor for gastric cancer. H. pylori harboring the type IV secretion system (T4SS) and its effector CagA encoded on the cag pathogenicity Island (cagPAI) increases the risk. H. pylori PMSS1 has a multi-cagA genotype, modulating cagA copy number dynamically from zero to four copies. To examine the effect of the immune response on cagA copy number change, we utilized a mouse model with different immune status. PMSS1 recovered from Rag1-/- mice, lacking functional T or B cells, retained more cagA copies. PMSS1 recovered from Il10-/- mice, showing intense inflammation, had fewer cagA copies compared to those recovered from wild-type mice. Moreover, cagA copy number of PMSS1 recovered from wild-type and Il10-/- mice was positively correlated with the capacity to induce IL-8 secretion at four weeks of infection. Since recombination in cagY influences T4SS function, including CagA translocation and IL-8 induction, we constructed a multiple linear regression model to predict H. pylori-induced IL-8 expression based on cagA copy number and cagY recombination status; H. pylori induces more IL-8 secretion when the strain has more cagA copies and intact cagY. This study shows that H. pylori PMSS1 in mice with less intense immune response possess higher cagA copy number than those infected in mice with more intense immune response and thus the multi-cagA genotype, along with cagY recombination, functions as an immune-sensitive regulator of H. pylori virulence.

BackgroundHelicobacter pylori is the most important risk factor for non-cardia gastric cancer (NCGC); however, the magnitude of the association varies across epidemiological studies. This study aimed to quantify the association between H. pylori infection and NCGC, using different criteria to define infection status.MethodsA pooled analysis of individual-level H. pylori serology data from eight international studies (1325 NCGC and 3121 controls) from the Stomach Cancer Pooling (StoP) Consortium was performed. Cases and controls with a negative H. pylori infection status were reclassified as positive considering the presence of anti-Cag A antibodies, gastric atrophy, or advanced stage at diagnosis, as available and applicable. A two-stage approach was used to pool study-specific adjusted odds ratios (OR), and 95% confidence intervals (95% CI). A meta-analysis of published prospective studies assessing H. pylori seropositivity in NCGCs was conducted.ResultsThe OR for the association between serology-defined H. pylori and NCGC was 1.45 (95% CI: 0.87-2.42), which increased to 4.79 (95% CI: 2.39-9.60) following the reclassification of negative H. pylori infection. The results were consistent across strata of sociodemographic characteristics, clinical features and lifestyle factors, though significant differences were observed according to geographic region-a stronger association in Asian studies. The pooled risk estimates from the literature were 3.01 (95% CI: 2.22-4.07) for ELISA or EIA and 9.22 (95% CI: 3.12-27.21) for immunoblot or multiplex serology.ConclusionThe NCGC risk estimate from StoP based on the reclassification of H. pylori seronegative individuals is consistent with the risk estimates obtained from the literature. Our classification algorithm may be useful for future studies.

BackgroundPrior epidemiologic studies on the association between diabetes and gastric cancer risk provided inconclusive findings, while traditional, aggregate data meta-analyses were characterized by high between-study heterogeneity.ObjectiveTo investigate the association between type 2 diabetes and gastric cancer using data from the 'Stomach Cancer Pooling (StoP) Project', an international consortium of more than 30 case-control and nested case-control studies, which is large and provides harmonized definition of participants' characteristics across individual studies. The data have the potential to minimize between-study heterogeneity and provide greater statistical power for subgroup analysis.MethodsWe included 5592 gastric cancer cases and 12 477 controls from 14 studies from Europe, Asia, North America, and South America in a two-stage individual-participant data meta-analysis. Random-effect models were used to estimate summary odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) by pooling study-specific ORs.ResultsWe did not find an overall association between diabetes and gastric cancer (pooled OR = 1.01, 95% CI, 0.94-1.07). However, the risk of cardia gastric cancer was significantly higher among individuals with type 2 diabetes (OR = 1.16, 95% CI, 1.02-1.33). There was no association between diabetes and gastric cancer risk in strata of Helicobacter pylori infection serostatus, age, sex, BMI, smoking status, alcohol consumption, fruit/vegetable intake, gastric cancer histologic type, and source of controls.ConclusionThis study provides additional evidence that diabetes is unrelated to gastric cancer overall but may be associated with excess cardia gastric cancer risk.

Gastric carcinogenesis is mediated by complex interactions among Helicobacter pylori, host, and environmental factors. Here, we demonstrate that H. pylori augmented gastric injury in INS-GAS mice under iron-deficient conditions. Mechanistically, these phenotypes were not driven by alterations in the gastric microbiota; however, discovery-based and targeted metabolomics revealed that bile acids were significantly altered in H. pylori-infected mice with iron deficiency, with significant upregulation of deoxycholic acid (DCA), a carcinogenic bile acid. The severity of gastric injury was further augmented when H. pylori-infected mice were treated with DCA, and, in vitro, DCA increased translocation of the H. pylori oncoprotein CagA into host cells. Conversely, bile acid sequestration attenuated H. pylori-induced injury under conditions of iron deficiency. To translate these findings to human populations, we evaluated the association between bile acid sequestrant use and gastric cancer risk in a large human cohort. Among 416,885 individuals, a significant dose-dependent reduction in risk was associated with cumulative bile acid sequestrant use. Further, expression of the bile acid receptor transmembrane G protein-coupled bile acid receptor 5 (TGR5) paralleled the severity of carcinogenic lesions in humans. These data demonstrate that increased H. pylori-induced injury within the context of iron deficiency is tightly linked to altered bile acid metabolism, which may promote gastric carcinogenesis.

Helicobacter pylori is the major risk factor for gastric cancer. H. pylori harboring the type IV secretion system (T4SS) and its effector CagA encoded on the cag pathogenicity Island (cagPAI) increases the risk. H. pylori PMSS1 has a multi-cagA genotype, modulating cagA copy number dynamically from zero to four copies. To examine the effect of the immune response on cagA copy number change, we utilized a mouse model with different immune status. PMSS1 recovered from Rag1-/- mice, lacking functional T or B cells, retained more cagA copies. PMSS1 recovered from Il10-/- mice, showing intense inflammation, had fewer cagA copies compared to those recovered from wild-type mice. Moreover, cagA copy number of PMSS1 recovered from wild-type and Il10-/- mice was positively correlated with the capacity to induce IL-8 secretion at four weeks of infection. Since recombination in cagY influences T4SS function, including CagA translocation and IL-8 induction, we constructed a multiple linear regression model to predict H. pylori-induced IL-8 expression based on cagA copy number and cagY recombination status; H. pylori induces more IL-8 secretion when the strain has more cagA copies and intact cagY. This study shows that H. pylori PMSS1 in mice with less intense immune response possess higher cagA copy number than those infected in mice with more intense immune response and thus the multi-cagA genotype, along with cagY recombination, functions as an immune-sensitive regulator of H. pylori virulence.

BackgroundPrior epidemiologic studies on the association between diabetes and gastric cancer risk provided inconclusive findings, while traditional, aggregate data meta-analyses were characterized by high between-study heterogeneity.ObjectiveTo investigate the association between type 2 diabetes and gastric cancer using data from the 'Stomach Cancer Pooling (StoP) Project', an international consortium of more than 30 case-control and nested case-control studies, which is large and provides harmonized definition of participants' characteristics across individual studies. The data have the potential to minimize between-study heterogeneity and provide greater statistical power for subgroup analysis.MethodsWe included 5592 gastric cancer cases and 12 477 controls from 14 studies from Europe, Asia, North America, and South America in a two-stage individual-participant data meta-analysis. Random-effect models were used to estimate summary odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) by pooling study-specific ORs.ResultsWe did not find an overall association between diabetes and gastric cancer (pooled OR = 1.01, 95% CI, 0.94-1.07). However, the risk of cardia gastric cancer was significantly higher among individuals with type 2 diabetes (OR = 1.16, 95% CI, 1.02-1.33). There was no association between diabetes and gastric cancer risk in strata of Helicobacter pylori infection serostatus, age, sex, BMI, smoking status, alcohol consumption, fruit/vegetable intake, gastric cancer histologic type, and source of controls.ConclusionThis study provides additional evidence that diabetes is unrelated to gastric cancer overall but may be associated with excess cardia gastric cancer risk.

Gastric carcinogenesis is mediated by complex interactions among Helicobacter pylori, host, and environmental factors. Here, we demonstrate that H. pylori augmented gastric injury in INS-GAS mice under iron-deficient conditions. Mechanistically, these phenotypes were not driven by alterations in the gastric microbiota; however, discovery-based and targeted metabolomics revealed that bile acids were significantly altered in H. pylori-infected mice with iron deficiency, with significant upregulation of deoxycholic acid (DCA), a carcinogenic bile acid. The severity of gastric injury was further augmented when H. pylori-infected mice were treated with DCA, and, in vitro, DCA increased translocation of the H. pylori oncoprotein CagA into host cells. Conversely, bile acid sequestration attenuated H. pylori-induced injury under conditions of iron deficiency. To translate these findings to human populations, we evaluated the association between bile acid sequestrant use and gastric cancer risk in a large human cohort. Among 416,885 individuals, a significant dose-dependent reduction in risk was associated with cumulative bile acid sequestrant use. Further, expression of the bile acid receptor transmembrane G protein-coupled bile acid receptor 5 (TGR5) paralleled the severity of carcinogenic lesions in humans. These data demonstrate that increased H. pylori-induced injury within the context of iron deficiency is tightly linked to altered bile acid metabolism, which may promote gastric carcinogenesis.

Background: Managing Helicobacter pylori infection requires constant decision making, and each decision is open to possible errors. Aim: The aim was to evaluate common mistakes in the eradication of H. pylori, based on the "European Registry on Helicobacter pylori management". Methods: European Registry on Helicobacter pylori management is an international multicentre prospective noninterventional registry evaluating the decisions and outcomes of H. pylori management by European gastroenterologists in routine clinical practice. Results: Countries recruiting more than 1000 patients were included (26,340 patients). The most common mistakes (percentages) were: (1) To use the standard triple therapy where it is ineffective (46%). (2) To prescribe eradication therapy for only 7 to 10 days (69%). (3) To use a low dose of proton pump inhibitors (48%). (4) In patients allergic to penicillin, to prescribe always a triple therapy with clarithromycin and metronidazole (38%). (5) To repeat certain antibiotics after eradication failure (>15%). (6) Failing to consider the importance of compliance with treatment (2%). (7) Not to check the eradication success (6%). Time-trend analyses showed progressive greater compliance with current clinical guidelines. Conclusion: The management of H. pylori infection by some European gastroenterologists is heterogeneous, frequently suboptimal and discrepant with current recommendations. Clinical practice is constantly adapting to updated recommendations, although this shift is delayed and slow.