ArticleScientific reports2020
Long-term Proton Pump Inhibitor Administration Caused Physiological and Microbiota Changes in Rats.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Efficacy and safety of probiotics combined with bismuth-containing quadruple therapy forFrontiers in microbiology · 2025Pooled it
- Using proton pump inhibitors increases the risk of hepato-biliary-pancreatic cancer. A systematic review and meta-analysis.Frontiers in pharmacology · 2022Pooled it
- Preoperative proton pump inhibitor therapy and its influence on postoperative complications following major liver resection.Langenbeck's archives of surgery · 2026Article
- Association Between Long-Term Proton Pump Inhibitor Use and Low-Risk Gastric Neuroendocrine Tumors.Annals of surgical oncology · 2026Article
- The association of proton pump inhibitors and inflammatory bowel disease from the perspective of gut microbiota perturbation.NPJ biofilms and microbiomes · 2025Review
- Matcha Green Tea Improves Cafeteria-Diet-Induced NAFLD by Modulating the Gut Microbiota in Rats.Nutrients · 2025Article
- Proton Pump Inhibitor Use in Older Adult Patients with Multiple Chronic Conditions: Clinical Risks and Best Practices.Journal of clinical medicine · 2025Review
- Proton Pump Inhibitors and Oral-Gut Microbiota: From Mechanism to Clinical Significance.Biomedicines · 2024Review
- Linking GERD and the Peptide Bombesin: A New Therapeutic Strategy to Modulate Inflammatory, Oxidative Stress and Clinical Biochemistry Parameters.Antioxidants (Basel, Switzerland) · 2024Article
- Gastric development of pancreatic acinar cell metaplasia after Vonoprazan therapy in rats.Surgical endoscopy · 2023Article
- Long-term potassium-competitive acid blockers administration causes microbiota changes in rats.Surgical endoscopy · 2023Article
- Intranasal administration of Lactobacillus johnsonii attenuates hyperoxia-induced lung injury by modulating gut microbiota in neonatal mice.Journal of biomedical science · 2023Article
- Long-Term Use of Proton Pump Inhibitors Disrupts Intestinal Tight Junction Barrier and Exaggerates Experimental Colitis.Journal of Crohn's & colitis · 2023Article
- A network perspective on the ecology of gut microbiota and progression of type 2 diabetes: Linkages to keystone taxa in a Mexican cohort.Frontiers in endocrinology · 2023Article
- Proton pump inhibitors may enhance the risk of digestive diseases by regulating intestinal microbiota.Frontiers in pharmacology · 2023Review
- Gut Microbiota Alterations in Trace Amine-Associated Receptor 9 (TAAR9) Knockout Rats.Biomolecules · 2022Article
- Uteroplacental Insufficiency Causes Microbiota Disruption and Lung Development Impairment in Growth-Restricted Newborn Rats.Nutrients · 2022Article
- Clinical significance and intestinal microbiota composition in immunocompromised children with norovirus gastroenteritis.PloS one · 2022Article
- Proton Pump Inhibitor Use Increases Pyogenic Liver Abscess Risk: A Nationwide Cohort Study.Journal of neurogastroenterology and motility · 2021Article
- Maternal antibiotic exposure disrupts microbiota and exacerbates hyperoxia-induced lung injury in neonatal mice.Pediatric research · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.