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

Abstract

Background/AimsTo evaluate changes in gut microbiota composition following long-term proton pump inhibitor (PPI) treatment.MethodsTwenty-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).ResultsRats 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.ConclusionsThis preliminary study suggests that long-term administration of PPI may cause weight loss and changes to the microbiota in the terminal ileum.

RETRACTED ARTICLE: Repertoire of the gut microbiota from stomach to colon using culturomics and next-generation sequencing

“…Moreover, PPI treatment results in modifications in the gut microbiota, with an increase in the Firmicutes population associated with a decrease in Bacteroidetes . Similarly, previous studies have revealed important microbiota changes in the terminal ileum with PPI administration, which can be summarized as an increase in Firmicutes ( Lactobacillus or Clostridium ) and/or a decrease in Bacteroidetes [ 34 , 35 ]. Furthermore, alterations in the gut microbiota (a decrease in Akkermansia and Coprococcus and an increase in Bacteroidales ) and weight loss after the administration of omeprazole in C57BL/6 J mice has been reported [ 36 ].…”

The protective effect of Bifidobacterium bifidum G9-1 against mucus degradation by Akkermansia muciniphila following small intestine injury caused by a proton pump inhibitor and aspirin

“…To examine the effects of PPIs in detail, we focused on the analysis of the microbiota in the jejunum. Prior studies have shown that PPI causes dysbiosis, increasing the levels of Lactobacillus and Streptococcus in ileum and fecal samples [27][28][29] while reducing Bifidobacteria levels in fecal samples; 30 we made a similar observation ( Figure S1, Figure 2, Figure S5). In the clinical study as shown in Figure 2a and S1, the relative abundance of Akkermansia was not changed.…”

The Gastric and Intestinal Microbiome: Role of Proton Pump Inhibitors

“…[116] In rat models, long-term use of lansoprazole (50 weeks) was associated with significant shift in terminal ileum bacterial composition: a predominance of Proteobacteria (93.9%, mainly Escherichia and Pasteurella genera) in the controls and the abundance of Firmicutes (66.9%, mainly Clostridium and Lactobacillus genera) in the treatment group. [117]…”