Project description:Chronic acid suppression by proton pump inhibitor (PPI) has been hypothesized to alter the gut microbiota via a change in intestinal pH. To evaluate the changes in gut microbiota composition by long-term PPI treatment.
Project description:Chronic acid suppression by proton pump inhibitor (PPI) has been hypothesized to alter the gut microbiota via a change in intestinal pH. To evaluate the changes in gut microbiota composition by long-term PPI treatment. Twenty-four week old F344 rats were fed with (n = 5) or without (n = 6) lansoprazole (PPI) for 50 weeks. Then, profiles of luminal microbiota in the terminal ileum were analyzed. Pyrosequencing for 16S rRNA gene was performed by genome sequencer FLX (454 Life Sciences/Roche) and analyzed by metagenomic bioinformatics.
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.
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.
Project description:Recent clinical studies indicated Proton-pump inhibitors (PPIs) but not H2 Receptor Antagonists were associated with a decreased risk of esophageal adenocarcinoma. We’d like to clarify whether PPIs interfere with Barrett’s esophagus(BE) pathogenesis during BE treatment and explore the novel roles of omeprazole beyond acid suppression. RNA deep-sequencing was conducted in BE organoids exposed to periodic bile acids(400µM, pH 5.5) stimulation with or without omeprazole(40µM)treatment. A total of 129 long non-coding RNAs, 20 microRNAs, and 285 mRNAs were significantly regulated. Then, bioinformatics tools and databases were employed to explore the potential functions and relationships of these RNAs. Our data showed that the most significantly involved pathways modulated by omeprazole were Phenylalanine metabolism and Glycosaminoglycan biosynthesis - keratan sulfate. In addition, the miRNA-mRNA-lncRNA network regulated by omeprazole was constructed. We have demonstrated some novel acid-independent mechanisms of omeprazole that might yield valuable insight into clinical management of BE, irrespective of acid reflux symptoms.
Project description:Purpose: The goals of this study were to evaluate the effects of acid suppression on the brain transcriptomer in a murine model of stress. In addition, the effects of the proton pump inhibitor (PPI), esomeprazole, on the brain transcriptome were evaluted in the presence or absence of stress. Methods: Male C57BL/6 mice were subjected to three days of stress by hypothermic immobilization or control environment for three hours daily and either esomeprazole 2 mg/kg or saline by intraperitoneal injection daily. Standard RNA-seq methods were employed to assess mRNA expression in the hippocampus and frontal cortex. Results: There was no effect of stress or esomeprazole on the frontal cortex transcriptome. Stress had no impact on the hippocampus transcriptome, but the addition of esomeprazole induced differential expression of 124 genes, many of which are involved in cognitive and behavior pathways. Conclusions: Further studies are needed to evaluate the associations between microbiota, host gene expression, the abundance of CNS neurocognitive modulators, and their impact on cognition and behavior.
Project description:The effect on mucosal gene expression of potent acid inhibition with proton pump inhibitors (PPI’s) given to humans in ordinary, therapeutic doses is virtually unknown. Eight patients suffering from gastro-oesophageal reflux disease were included in this study. Endoscopic biopsies were taken from the corpus mucosa before and towards the end of a three-month treatment with the PPI esomeprazole 40 mg daily. Total RNA was extracted and samples (2 microgram total RNA) were labeled for microarray analysis. For each patient, RNA from both time points were labeled and hybridized to a single array. The gene expression patterns for 7700 genes were analyzed and differentially expressed genes were identified using one-sample Student t test. The aim of this study was, by use of cDNA microarray, to get an overview of the gene expression pattern in gastric corpus mucosa in patients after three months’ treatment with the proton pump inhibitor esomeprazole. Further characterization of the functional roles of genes whose expression is modulated by potent acid inhibition may give new insight into the molecular responses to this therapeutic intervention, including the mucosal response to the moderately increased gastrin levels encountered in clinical practice. Keywords: Repeat sample group, treatment analysis
2005-11-01 | GSE3240 | GEO
Project description:Effect of proton pump inhibitor on methanogenesis in anaerobic digestion of tryptone
Project description:Background & Aims: Because the pathophysiology of GERD is not fully understood, presently used drug target only one or more of the known underlying mechanisms but are not fully effective in all patients. 1Identifying novel central targets may pave the way to develop more effective agents. Methods: A surgical model of sub-chronic reflux esophagitis was developed. Wistar rats were pretreated for 7days with omeprazole (standard proton pump inhibitor) or STW5 (herbal preparation of established efficacy in gastro-intestinal disorders). Treatment was continued for 10days after surgery, rats were sacrificed and esophagi excised. Histological, proteomic and transcriptomic methods were applied to identify reflux induced changes and treatment responses. Results: Protection against reflux induced inflammation was achieved by both test drugs. Both reduced macroscopic and microscopic lesions of the esophagi as well as most measured pro-inflammatory cytokines without significantly affecting NF-kB activity. Proteomic and transcriptomic analysis identified CINC1-3, MIP-1/3α, MIG, RANTES and IL-1β as highly relevant mediators in GERD. Other highly regulated genes were those of IL-6, CCL3, CCL7 and LOX-1. Many affected cyto-/chemokines were involved in the TREM-1 signaling pathway. The fatty acid receptor GPR84 was highly up-regulated in esophagitis but down-regulated by both drugs. This was confirmed by Western blot and immune-histochemical staining, showing for the first time expression of this receptor in esophageal tissue and its possible involvement in GERD. Conclusion: STW5 and omeprazole target a broad spectrum of molecules involved in immunological and inflammatory processes, of which IL-8 (CINC1-3), TREM-1 pathway and GPR84 are proposed to be most promising novel targets for the treatment of GERD. Refluxesophagitis was surgically induced. Wistar rats were pretreated for 7 days with omeprazole or STW5. Treatment was continued for 10days after surgery, rats were sacrificed and esophagi exiced. The study had 5 groups. Group 1: sham operated, Group 2: esophagitis group, untreated, Group3: esophagitis treated with STW5 0.5ml/kg. Group 4: esophagitis treated with STW5 2ml/kg. Group 5: esophagitis treated with Omeprazole (30mg/kg). 4 microarrays from esophageal tissue and blood from 4 animals of each group were performed.