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Long-term Proton Pump Inhibitor Administration Caused Physiological and Microbiota Changes in Rats

ABSTRACT: Long-term Proton Pump Inhibitor Administration Caused Physiological and Microbiota Changes in Rats

PROVIDER: PRJEB28574 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR2785660_1.fastq.gz	Fastqsanger.gz
	ERR2785660_2.fastq.gz	Fastqsanger.gz
	ERR2785651_1.fastq.gz	Fastqsanger.gz
	ERR2785651_2.fastq.gz	Fastqsanger.gz
	ERR2785661_1.fastq.gz	Fastqsanger.gz

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Transcript profiling of Arabidopsis plasma membrane proton pump mutants

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Transcript profiling of Arabidopsis plasma membrane proton pump mutants

Project description:Plasma membrane proton pump maintains proton electrochemical gradient and provides energy to secondary transporters. Arabidopsis mutant plants with reduced proton pump activity grow normal under ideal growth conditions; however their growth are reduced compared with wildtype plants when placed under the conditions that stress on protonmotive force (high external pH or high external potassium). Seedlings of wildtype, aha1, and aha2 mutant plants were grown under ideal growth condition. Total RNA from those seedlings were subjected to transcriptome analyses using Affymetrix Gene Chip.

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Proton pump inhibitors modulate the barrier dysfunction caused by IL-13 in the epithelium in eosinophilic esophagitis

Project description:Proton pump inhibitors modulate the barrier dysfunction caused by IL-13 in the epithelium in eosinophilic esophagitis

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Proton pump inhibitors modulate the barrier dysfunction caused by IL-13 in the epithelium in eosinophilic esophagitis

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

Long-term Proton Pump Inhibitor Administration Caused Physiological and Microbiota Changes in Rats.

Project description:Proton pump inhibitors (PPIs) are used for the long-term treatment of gastroesophageal disorders and the non-prescription medicines for acid reflux. However, there is growing concerns about PPI misuse, overuse and abuse. This study aimed to develop an animal model to examine the effects of long-term use of PPI in vivo. Twenty one Wistar rats were given omeprazole orally or intravenously for 30 days, and caerulein as a positive control. After euthanization, the serum and stool were collected to perform MS-based quantitative analysis of metabolites. We carried out 16S-based profiling of fecal microbiota, assessed the expression of bile acid metabolism regulators and examined the immunopathological characteristics of bile ducts. After long-term PPI exposure, the fecal microbial profile was altered and showed similarity to those observed in high-fat diet studies. The concentrations of several metabolites were also changed in various specimens. Surprisingly, morphological changes were observed in the bile duct, including ductal epithelial proliferation, micropapillary growth of biliary epithelium, focal bile duct stricture formation and bile duct obstruction. These are characteristics of precancerous lesions of bile duct. FXR and RXRα expressions were significantly reduced, which were similar to that observed in cholangiocarcinoma in TCGA and Oncomine databases. We established a novel animal model to examine the effects of long-term use of omeprazole. The gut microbes and metabolic change are consequences of long-term PPI exposure. And the results showed the environment in vivo tends to a high-fat diet. More importantly, we observed biliary epithelial hyperplasia, which is an indicator of a high-fat diet.

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Proton pump inhibitor treatment aggravates bacterial translocation in patients with advanced liver cirrhosis and portal hypertension

Project description:Blood microbiome and proton pump inhibitor treatment

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Expression data from young and senescent HCAECs treated with proton pump inhibitors (omeprazole and lansoprazole)

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

Targeting ATP12A, a non-gastric proton pump alpha subunit, for idiopathic pulmonary fibrosis treatment

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Transcriptional profiling of Mycobacterium tuberculosis exposed to proton pump inhibitor treatment in broth culture.

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Targeting ATP12A, a non-gastric proton pump alpha subunit, for idiopathic pulmonary fibrosis treatment

Project description:Idiopathic Pulmonary Fibrosis (IPF) is a pathological condition of unknown etiology which results from injury to the lung and an ensuing fibrotic response that leads to thickening of the alveolar walls and obliteration of the alveolar space. The pathogenesis is not clear and there are currently no effective therapies for IPF. Small airway disease and mucus accumulation are prominent features in IPF lungs, similar to Cystic Fibrosis (CF) lung disease. The ATP12A gene encodes the alpha-subunit of the non-gastric H+, K+-ATPase, which functions to acidify the airway surface fluid and impairs mucociliary transport function in cystic fibrosis patients. We hypothesize that the ATP12A protein may play a role in the pathogenesis of IPF. Our studies demonstrate that ATP12A protein is overexpressed in distal small airways from IPF patient lungs compared to normal human lungs. In addition, overexpression of the ATP12A protein in mouse lungs worsened the bleomycin (BLEO)-induced experimental pulmonary fibrosis. This was prevented by a potassium-competitive proton pump blocker, vonoprazan (VON). This data supports the concept that the ATP12A protein plays an important role in the pathogenesis of lung fibrosis. Inhibition of the ATP12A protein has the potential as a novel therapeutic strategy in IPF.

2023-04-01 | GSE205849 | GEO

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