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, 10 (6), 896-901

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


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

Cheol Min Shin et al. Gut Liver.


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.

Keywords: Clostridium; Gastrointestinal microbiome; Proton pump inhibitors; Small bowel intestinal overgrowth.


Fig. 1
Fig. 1
Distribution of the phyla in different samples from the terminal ileum. (A) C2-13, C2-14, C2-15, C2-16 and C2-17 belong to the control group, and L2-B1, L2-B3, L2-B5, L2-H2, L2-H4, L2-H8 belong to the proton pump inhibitor (PPI)-treated group. (B) The composition of the gut microbiota in PPI-treated rats was quite different from that of the controls. The major phyla were Proteobacteria in the controls and Firmicutes in the PPI-treated rats.
Fig. 2
Fig. 2
Fast UniFrac analysis for the comparison of the microbial communities (unweighted pair group method with arithmetic mean dendrogram) that identified four distinct groups (I, II, III, and IV).
Fig. 3
Fig. 3
Circular heat map analysis of phyla (A) and genera (B). Each taxon and its proportion are represented by a circle (area), with a minimum ratio for inclusion of 5%. PPI, proton pump inhibitor.

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