Gut Liver.  2016 Nov;10(6):896-901. 10.5009/gnl15529.

Impact of Long-Term Proton Pump Inhibitor Therapy on Gut Microbiota in F344 Rats: Pilot Study

Affiliations
  • 1Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. nayoungkim49@empas.com
  • 2Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  • 3Gastroenterology and Digestive Disease Research Institute, Wonkwang University School of Medicine, Iksan, Korea.
  • 4Department of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, Korea.
  • 5Life Science R&D Center, SK Chemicals, Seongnam, Korea.
  • 6NAR Center, Inc., Daejeon Oriental Hospital of Daejeon University, Daejeon, Korea.

Abstract

BACKGROUND/AIMS
To evaluate changes in gut microbiota composition following long-term proton pump inhibitor (PPI) treatment.
METHODS
Twenty-four-week-old F344 rats were fed diets with (n=6) or without (n=5) lansoprazole for 50 weeks. Profiles of luminal microbiota in the terminal ileum were then analyzed. Pyrosequencing of the 16S rRNA gene was performed using an FLX genome sequencer (454 Life Sciences/Roche).
RESULTS
Rats treated with lansoprazole showed significantly reduced body weights compared to controls (lansoprazole-treated rats and controls, 322.3±15.3 g vs 403.2±5.2 g, respectively, p<0.001). However, stool frequencies and consistencies did not differ between the two groups. The composition of the gut microbiota in lansoprazole-treated rats was quite different from that of the controls. In the controls, the microbiota profiles obtained from the terminal ileum showed a predominance of Proteobacteria (93.9%) due to the abundance of Escherichia and Pasteurella genera. Conversely, lansoprazole-treated rats showed an elevated population of Firmicutes (66.9%), which was attributed to an increased ratio of Clostridium g4 to Lactobacillus genera.
CONCLUSIONS
This preliminary study suggests that long-term administration of PPI may cause weight loss and changes to the microbiota in the terminal ileum.

Keyword

Proton pump inhibitors; Gastrointestinal microbiome; Small bowel intestinal overgrowth; Clostridium

MeSH Terms

Animals
Gastrointestinal Microbiome/*drug effects
Ileum/drug effects/microbiology
Lansoprazole/*pharmacology
Male
Pilot Projects
Proton Pump Inhibitors/*pharmacology
RNA, Ribosomal, 16S/genetics
Rats
Rats, Inbred F344
Sequence Analysis, DNA/methods
Time
Proton Pump Inhibitors
RNA, Ribosomal, 16S
Lansoprazole
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