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Long-term potassium-competitive acid blockers administration causes microbiota changes in rats

  • 2023 SAGES Oral
  • Published:
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Abstract

Background

Vonoprazan is a new potassium-competitive acid blocker (P-CAB) that was recently approved by the FDA. It is associated with a fast onset of action and a longer acid inhibition time. Vonoprazan-containing therapy for helicobacter pylori eradication is highly effective and several studies have demonstrated that a vonoprazan-antibiotic regimen affects gut microbiota. However, the impact of vonoprazan alone on gut microbiota is still unclear.

Methods

We conducted a prospective randomized 12-week experimental trial with 18 Wistar rats. Rats were randomly assigned to one of 3 groups: (1) drinking water as negative control group, (2) oral vonoprazan (4 mg/kg) for 12 weeks, and (3) oral vonoprazan (4 mg/kg) for 4 weeks, followed by 8 weeks off vonoprazan. To investigate gut microbiota, we carried out a metagenomic shotgun sequencing of fecal samples at week 0 and week 12.

Results

For alpha diversity metrics at week 12, both long and short vonoprazan groups had lower Pielou’s evenness index than the control group (p = 0.019); however, observed operational taxonomic units (p = 0.332) and Shannon’s diversity index (p = 0.070) were not statistically different between groups. Beta diversity was significantly different in the three groups, using Bray–Curtis (p = 0.003) and Jaccard distances (p = 0.002). At week 12, differences in relative abundance were observed at all levels. At phylum level, short vonoprazan group had less of Actinobacteria (log fold change = − 1.88, adjusted p-value = 0.048) and Verrucomicrobia (lfc = − 1.76, p = 0.009).

At the genus level, long vonoprazan group had more Bacteroidales (lfc = 5.01, p = 0.021) and Prevotella (lfc = 7.79, p = 0.001). At family level, long vonoprazan group had more Lactobacillaceae (lfc = 0.97, p = 0.001), Prevotellaceae (lfc = 8.01, p < 0.001), and less Erysipelotrichaceae (lfc = − 2.9, p = 0.029).

Conclusion

This study provides evidence that vonoprazan impacts the gut microbiota and permits a precise delineation of the composition and relative abundance of the bacteria at all different taxonomic levels.

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Funding

This study was internally funded.

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Author notes

  1. Haythem Najah and Rodrigo C. L. Edelmuth have contributed equally to this work.

Authors and Affiliations

  1. Division of Endocrine & Minimally Invasive Surgery, Department of Surgery, New York-Presbyterian Hospital, Weill Cornell Medical College, 525 East 68th Street, K-836, New York, NY, 10065, USA

    Haythem Najah, Rodrigo C. L. Edelmuth, Maria Cristina Riascos, Hala Al Asadi, Jacques A. Greenberg, Brendan M. Finnerty, Thomas J. Fahey III & Rasa Zarnegar

  2. Microbiome Core Lab of Weill Cornell Medicine, New York, NY, USA

    Alex Grier

  3. Laboratory of Comparative Pathology (LCP), Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, The Rockefeller University, New York, NY, USA

    Ileana Miranda

  4. Division of Gastroenterology and Hepatology, Department of Medicine, New York-Presbyterian Hospital, Weill Cornell Medical College, New York, NY, USA

    Carl V. Crawford

  5. Hospital Israelita Albert Einstein, São Paulo, Brazil

    Rodrigo C. L. Edelmuth

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Correspondence to Haythem Najah.

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Dr. Rasa Zarnegar works as a consultant for Bard (BD). Drs. Haythem Najah, Rodrigo C.L. Edelmuth, Maria Cristina Riascos, Alex Grier, Hala Al Asadi, Jacques A. Greenberg, Ileana Miranda, Carl V. Crawford, Brendan M. Finnerty, and Thomas J. Fahey III have no conflicts of interest or financial ties to disclose.

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Najah, H., Edelmuth, R.C.L., Riascos, M.C. et al. Long-term potassium-competitive acid blockers administration causes microbiota changes in rats. Surg Endosc 37, 7980–7990 (2023). https://doi.org/10.1007/s00464-023-10269-6

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