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

Yu-Chen S H Yang1, Hsuen-Wen Chang2, I-Hsuan Lin3

  • 1Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan.

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|January 23, 2020
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Summary
This summary is machine-generated.

Long-term proton pump inhibitor (PPI) use alters gut microbes and metabolites, mimicking a high-fat diet. This study reveals precancerous bile duct changes, highlighting potential risks of prolonged PPI medication.

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Area of Science:

  • Gastroenterology and Hepatology
  • Microbiome Research
  • Drug Safety and Toxicology

Background:

  • Proton pump inhibitors (PPIs) are widely used for acid reflux and gastroesophageal disorders.
  • Concerns exist regarding the misuse, overuse, and potential adverse effects of long-term PPI therapy.
  • Existing research lacks comprehensive in vivo models to assess these long-term impacts.

Purpose of the Study:

  • To develop and validate a novel animal model for investigating the in vivo effects of long-term proton pump inhibitor (PPI) exposure.
  • To analyze the impact of omeprazole on gut microbiota, host metabolism, and biliary system pathology.
  • To explore potential links between PPI-induced changes and precancerous conditions.

Main Methods:

  • Administered omeprazole to Wistar rats for 30 days, with caerulein as a positive control.
  • Utilized mass spectrometry (MS) for quantitative metabolite analysis in serum and stool.
  • Performed 16S rRNA gene sequencing for fecal microbiota profiling and assessed bile acid metabolism regulators (FXR, RXRα).

Main Results:

  • Long-term PPI exposure significantly altered fecal microbial composition, resembling patterns seen in high-fat diet studies.
  • Significant changes in serum and fecal metabolite concentrations were observed.
  • Morphological analysis revealed precancerous bile duct lesions, including epithelial proliferation, micropapillary growth, stricture, and obstruction.
  • Reduced FXR and RXRα expression correlated with cholangiocarcinoma signatures in public databases.

Conclusions:

  • Established a novel rat model demonstrating that long-term omeprazole use induces significant gut microbiome and metabolic alterations.
  • The observed changes create an in vivo environment conducive to high-fat diet-like conditions.
  • Crucially, the model identified biliary epithelial hyperplasia, a precancerous indicator, suggesting potential long-term risks associated with PPIs.