Long-term changes in microbiome of infant users of proton-pump inhibitors
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PROVIDER: PRJEB56662 | ENA |
REPOSITORIES: ENA
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Project description:Eosinophilic esophagitis (EoE) is a chronic immune-mediated disorder triggered by specific food antigens, characterized by eosinophil-rich multicellular inflammation and structural changes in the epithelium. Treatment options for EoE include dietary therapy, pharmacological therapy, or a combination of both, chosen based on the patient's preference and clinical progression. Pharmacological options include proton pump inhibitors (PPIs), corticosteroids, and biologic therapy. Although PPI therapy is used for EoE management, its underlying mechanism of action remains unclear. To investigate the effects of omeprazole, an orally bioavailable PPI commonly used for EoE therapy, on the dynamics of esophageal epithelial barrier function and inflammation, we employed air-liquid interface (ALI) culture. We examined how omeprazole affects gene expression changes caused by IL-13 treatment. ALI cultures were treated with 100 ng/ml of IL-13 and/or 50 µM of acid-activated omeprazole for 96 hours, and bulk RNA sequencing was performed to analyze the epithelial-specific transcriptomes of IL-13 and/or omeprazole-treated ALI. Our findings suggest potential gene interactions where omeprazole may mitigate transcriptional changes induced by IL-13, indicating that omeprazole may attenuate IL-13 mediated epithelial dysfunction relevant to EoE pathophysiology by modulating pathways associated with inflammation, tissue repair, and cell-cell communication.
2024-09-13 | GSE273039 | GEO
Project description:Proton pump inhibitors (PPIs) are among the most frequently prescribed drugs, especially in older people. Although these drugs are usually considered safe, recent evidence suggests that high dose and/or long term use of PPIs may have several detrimental effects, including increased risk of adverse cardiovascular events. The impact of PPI in the aging host environment still need to be characterized. Aged tissues, including vascular tissues, accumulate senescent cells that can communicate with their environment by secreting a myriad of cytokines and growth factors. Human coronary artery endothelial cells (HCAECs) provide an excellent model system to study â??in vitroâ?? most aspects of cardiovascular function and disease related to cellular senescence. The purpose of this study is thus to investigate the in vitro effects of two well-known PPIs (Omeprazole and Lansoprazole) on endothelial gene expression in senescent e non-senescent HCAECs. We used a cDNA microarray method to compare gene expression profiles of young and senescent HCAECs treated with omeprazole and lansoprazole. Young cells were cultured in medium supplemented with vehicle (CTRL) or 100μM PPIs (Omeprazole or Lansoprazole) and grown for subsequent passages until they evidenced senescence-associated phenotypes. Total mRNA was extracted and gene expression profiles were analyzed in senescent endothelial cells (P12) compared to the non-senescent cells (P6) in both untreated (CTRL) and PPI-treated groups by cDNA microarray. All experiments were performed in triplicate for each treatment group.
2017-04-18 | E-GEOD-77239 | biostudies-arrayexpress
Project description:Proton pump inhibitors (PPIs) are among the most frequently prescribed drugs, especially in older people. Although these drugs are usually considered safe, recent evidence suggests that high dose and/or long term use of PPIs may have several detrimental effects, including increased risk of adverse cardiovascular events. The impact of PPI in the aging host environment still need to be characterized. Aged tissues, including vascular tissues, accumulate senescent cells that can communicate with their environment by secreting a myriad of cytokines and growth factors. Human coronary artery endothelial cells (HCAECs) provide an excellent model system to study “in vitro” most aspects of cardiovascular function and disease related to cellular senescence. The purpose of this study is thus to investigate the in vitro effects of two well-known PPIs (Omeprazole and Lansoprazole) on endothelial gene expression in senescent e non-senescent HCAECs. We used a cDNA microarray method to compare gene expression profiles of young and senescent HCAECs treated with omeprazole and lansoprazole.
2017-04-18 | GSE77239 | GEO
Project description:Proton pump inhibitors (PPIs) and corticosteroids are commonly prescribed drugs; however, each has been associated with fracture and community-acquired pneumonia. How physicians select patients for co-therapy may have implications for potential additive or synergistic toxicities.We conducted a retrospective cohort study of 13?749 incident corticosteroid users with no prior PPI exposure using the HealthCore Integrated Research Database(SM) . We used logistic regression to evaluate the association between PPI initiation in the first 30?days of steroid therapy and corticosteroid dose, clinical risk factors including comorbid diseases, and medication use including prescription nonsteroidal anti-inflammatory drugs (NSAIDs).A new PPI prescription within 30?days of starting corticosteroids was filled by 1050 patients (7.6%). PPI use was associated with the number of baseline comorbid conditions (OR?=?1.21 for each additional condition, 95%CI?=?1.13-1.28), recent hospitalization (OR?=?4.71, 95%CI?=?4.02-5.52), prednisone dose higher than 40?mg/day (OR?=?1.87, 95%CI?=?1.45-2.41), history of gastroesophageal reflux or gastric ulcer disease (OR?=?1.54, 95%CI?=?1.24-1.91), renal insufficiency (OR?=?2.06, 95%CI?=?1.73-2.46), and liver disease (OR?=?1.82, 95%CI?=?1.45-2.28). The concomitant use of prescription NSAIDs was also associated with PPI use (OR?=?1.89, 95%CI?=?1.32-2.70); however, the total use of PPIs in this group was low (6.3%, 95%CI?=?4.4-8.2%).Overall, PPI therapy among corticosteroid users was uncommon, even among those with risk factors for gastrointestinal toxicity. PPI use was significantly more common among patients who had recently been hospitalized, had a greater burden of comorbid illness, or were receiving high daily doses of corticosteroids.
| S-EPMC3970554 | biostudies-literature
Project description:There is controversy and little information about whether individual proton pump inhibitors (PPIs) differentially alter the effectiveness of clopidogrel in reducing ischemic stroke risk. We, therefore, aimed to elucidate the risk of ischemic stroke among concomitant users of clopidogrel and individual PPIs.We conducted a propensity score-adjusted cohort study of adult new users of clopidogrel, using 1999 to 2009 Medicaid claims from 5 large states. Exposures were defined by prescriptions for esomeprazole, lansoprazole, omeprazole, rabeprazole, and pantoprazole-with pantoprazole serving as the referent. The end point was hospitalization for acute ischemic stroke, defined by International Classification of Diseases Ninth Revision Clinical Modification codes in the principal position on inpatient claims, within 180 days of concomitant therapy initiation.Among 325 559 concomitant users of clopidogrel and a PPI, we identified 1667 ischemic strokes for an annual incidence of 2.4% (95% confidence interval, 2.3-2.5). Adjusted hazard ratios for ischemic stroke versus pantoprazole were 0.98 (0.82-1.17) for esomeprazole; 1.06 (0.92-1.21) for lansoprazole; 0.98 (0.85-1.15) for omeprazole; and 0.85 (0.63-1.13) for rabeprazole.PPIs of interest did not increase the rate of ischemic stroke among clopidogrel users when compared with pantoprazole, a PPI thought to be devoid of the potential to interact with clopidogrel.
| S-EPMC4342326 | biostudies-literature
Project description:ObjectivesProton pump inhibitors (PPIs) are widely prescribed medications for gastric acid-induced diseases. Despite the effectiveness of PPIs, recent evidence suggested an increased risk of various bacterial infections in PPI users. The current study was conducted to evaluate the risk of biliary infection after endoscopic biliary stent placement in regular users of PPIs.MethodsConsecutive patients with a native papilla who underwent endoscopic retrograde cholangiopancreatography and stent placement for biliary stricture between January 2010 and August 2019 were included in this retrospective study. The cumulative incidences of biliary infection were compared between regular and non-regular PPI users.ResultsDuring the study period, 270 regular PPI users and 146 non-regular PPI users were included in the analyses. Age, gender, and indication of endoscopic retrograde cholangiopancreatography were not different between the two groups. The incidences of biliary infection were 43% in regular PPI users and 36% in non-regular PPI users but the time to biliary infection was significantly shorter in regular PPI users than in non-regular users (28 vs. 87 days, p = 0.01). The cumulative incidence of biliary infection was significantly higher in regular PPI users compared with non-regular users (p = 0.008). The multivariable Cox regression analysis also showed a significantly higher hazard ratio of biliary infection in regular PPI users (1.62 [95% confidence interval 1.16-2.26; p = 0.005]).ConclusionsRegular PPI use was associated with a higher risk of biliary infection after endoscopic biliary drainage. Inappropriate PPI use should be avoided.
| S-EPMC9307719 | biostudies-literature
Project description:RATIONALE:Proton pump inhibitors (PPIs) are popular drugs for gastroesophageal reflux, which are now available for long-term use without medical supervision. Recent reports suggest that PPI use is associated with cardiovascular, renal, and neurological morbidity. OBJECTIVE:To study the long-term effect of PPIs on endothelial dysfunction and senescence and investigate the mechanism involved in PPI-induced vascular dysfunction. METHODS AND RESULTS:Chronic exposure to PPIs impaired endothelial function and accelerated human endothelial senescence by reducing telomere length. CONCLUSIONS:Our data may provide a unifying mechanism for the association of PPI use with increased risk of cardiovascular, renal, and neurological morbidity and mortality.
| S-EPMC4902745 | biostudies-literature
Project description:ObjectiveDetermine the adherence to recommendations of concomitant proton-pump inhibitor (PPI) treatment in regular low-dose of aspirin (LDASA) users, taking factors associated with the probability of receiving a PPI into account.DesignCohort study.SettingData were obtained from 120 Dutch primary care centres participating in the Netherlands Information Network of Primary Care (LINH).ParticipantsPatients 18 years and older who were regularly prescribed LDASA (30-325 mg) in 2008-2010 were included.Main outcome measuresRegular medication use was defined as receiving each consecutive prescription within 6 months after the previous one. Based on national guidelines, we categorised LDASA users into low and high gastrointestinal (GI) risk. A multilevel multivariable logistic regression analysis was applied to identify patient characteristics that influenced on the probability of regular PPI prescriptions.ResultsWe identified 12 343 patients who started LDASA treatment, of whom 3213 (26%) were at increased risk of GI complications. In this group, concomitant regular use of PPI was 46%, 36% did not receive PPI prescriptions and 18% obtained prescriptions irregularly (p<0.0001). The chance to obtain regularly PPI prescriptions versus no PPI was significantly influenced by, among others, previous GI complications (OR 13.9 (95% CI 11.8 to 16.4)), use of non-steroidal anti-inflammatory drugs (OR 5.2 (4.3 to 6.3)), glucocorticosteroids (6.1 (4.6 to 8.0)), selective serotonin reuptake inhibitors (9.1 (6.7 to 12.2)), drugs for functional GI disorders (2.4 (1.9 to 3.0)) and increased age.ConclusionsPrimary care physicians do not fully adhere to the current recommendations to prescribe PPIs regularly to LDASA users with an increased GI risk. More than 50% of the patients with an increased GI risk are not treated sufficiently with a concomitant PPI, increasing the risk of GI side effects. This finding underlines the necessity to consider merging recommendations into one common, standard and frequently used recommendation by primary care physicians.
| S-EPMC3731714 | biostudies-literature
Project description:ObjectivesTo estimate associations between long-term use of proton pump inhibitors (PPIs) and pneumonia incidence in older adults in primary care.DesignLongitudinal analyses of electronic medical records.SettingEngland PARTICIPANTS: Individuals aged 60 and older in primary care receiving PPIs for 1 year or longer (N=75,050) and age- and sex-matched controls (N=75,050).MeasurementsNet hazard ratios for pneumonia incidence in Year 2 of treatment were estimated using the prior event rate ratio (PERR), which adjusts for pneumonia incidence differences before initiation of treatment. Inverse probability weighted models adjusted for 78 demographic, disease, medication, and healthcare usage measures.ResultsDuring the second year after initiating treatment, PPIs were associated with greater hazard of incident pneumonia (PERR-adjusted hazard ratio=1.82, 95% confidence interval=1.27-2.54), accounting for pretreatment pneumonia rates. Estimates were similar across age and comorbidity subgroups. Similar results were also obtained from propensity score- and inverse probability-weighted models.ConclusionIn a large cohort of older adults in primary care, PPI prescription was associated with greater risk of pneumonia in the second year of treatment. Results were robust across alternative analysis approaches. Controversies about the validity of reported short-term harms of PPIs should not divert attention from potential long-term effects of PPI prescriptions on older adults.
| S-EPMC6099478 | biostudies-literature
Project description:BackgroundProton pump inhibitors (PPIs) are a first-line treatment for EoE, but data are limited concerning response durability. We aimed to determine long-term outcomes in EoE patients responsive to PPI-therapy.MethodsWe conducted a retrospective cohort study of newly diagnosed adults with EoE who had initial histologic response (<15 eosinophils per high-power-field) to PPI-only therapy. We extracted data regarding their subsequent clinical course and outcomes. We compared findings between the initial PPI-response endoscopy and the final endoscopy, and assessed factors associated with loss of PPI response.ResultsOf 138 EoE patients with initial histologic response to PPI, 50 had long-term endoscopic follow-up, 40 had clinical follow-up, 10 changed treatments, and 38 had no long-term follow-up. Of those with endoscopic follow-up, mean follow-up-time was 3.6 ± 2.9 years; 30 and 32 patients (60%; 64%) maintained histologic and symptom responses, respectively. However, fibrotic endoscopic findings of EoE were unchanged. Younger age (aOR 1.05, 95% CI: 1.01-1.11) and dilation prior to PPI treatment (aOR 0.21, 95% CI: 0.05-0.83) were the only factors associated with long-term loss of PPI response.ConclusionsLong-term histologic and clinical response rates for PPI therapy were 60% and 64%, respectively. Younger age and dilation at baseline were associated with histologic loss of response. These data can inform long-term EoE treatment selection.
| S-EPMC9427674 | biostudies-literature