Long-term Proton Pump Inhibitor Administration Caused Physiological and Microbiota Changes in Rats
| العنوان: | Long-term Proton Pump Inhibitor Administration Caused Physiological and Microbiota Changes in Rats |
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| المؤلفون: | Li-Nien Chien, Yun Yen, Wei Jia, Guoxiang Xie, Peiguo G. Chu, Min-Ju Wu, Vincent H.S. Chang, Yun-Ru Liu, Yu-Chen S. H. Yang, I-Hsuan Lin, Hsuen-Wen Chang, Fangcong Dong |
| المصدر: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-11 (2020) |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.drug_class, alpha-Tocopherol, lcsh:Medicine, Proton-pump inhibitor, Administration, Oral, Microbial communities, Pharmacology, Article, Cholangiocarcinoma, 03 medical and health sciences, Feces, 0302 clinical medicine, In vivo, RNA, Ribosomal, 16S, medicine, Animals, Humans, Epithelial proliferation, Rats, Wistar, lcsh:Science, Omeprazole, Multidisciplinary, Cholestasis, Retinoid X Receptor alpha, Bile duct, business.industry, Biliary epithelial hyperplasia, lcsh:R, Reflux, RNA-Binding Proteins, Proton Pump Inhibitors, Gastrointestinal Microbiome, Experimental models of disease, 030104 developmental biology, medicine.anatomical_structure, Cell Transformation, Neoplastic, Bile Duct Neoplasms, Gene Expression Regulation, 030220 oncology & carcinogenesis, Tyrosine, lcsh:Q, Bile Ducts, business, medicine.drug |
| الوصف: | 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. |
| وصف الملف: | application/pdf; application/msword |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::54fc446444cd9f0ff33ab2ac77084aadTest https://pubmed.ncbi.nlm.nih.gov/31964941Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....54fc446444cd9f0ff33ab2ac77084aad |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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