MICROBIOME CHANGES INDUCED BY OMEPRAZOLE AND VONOPRAZAN: AN ANIMAL MODEL
Maria Cristina Riascos*1, Rodrigo C. Edelmuth1,2, Hala Al Asadi1, Alexander Grier1, Abhinay Tumati1, Carl V. Crawford1, Brendan M. Finnerty1, Thomas J. Fahey1, Rasa Zarnegar1
1Weill Cornell Medicine, New York, NY; 2Sociedade Beneficente Israelita Brasileira Albert Einstein, Sao Paulo, São Paulo, Brazil
Introduction
Proton pump inhibitors (PPIs) are commonly used for the treatment of peptic ulcers and gastroesophageal reflux disease. Vonoprazan (VPZ) is a novel potassium-competitive acid blocker is reported to be highly effective in treating reflux. Recent studies have identified associated changes between GI microbiota and PPI use showing lower abundance in gut commensals and lower microbial diversity. We aim to evaluate the impact of VPZ as compared to PPIs on gut microbiome.
Methods
A prospective randomized long-term (12 weeks) experiment with 18 Wistar rats was conducted. At six weeks of age, rats were randomly assigned to one of 3 groups: (1) saline as control group, (2) oral Omeprazole (OPZ) (4 mg/kg), and (3) oral VPZ (4 mg/kg) for 12 weeks. Each group consisted of 6 animals. The goal of this study was to assess microbiome changes upon long-term administration of OPZ and VPZ. Alpha and beta diversity were calculated using Observed features and Bray Curtis methods, respectively. Differential abundance and log fold changes by taxonomy levels were calculated.
Results
Compared to the control group, OPZ had a significantly higher microbial pairwise beta diversity between time points week 0 and 12 (p=0.04) while VPZ showed no difference (p=0.82). However, compared to the control group, the microbiota's beta diversity between groups at week 12 showed OPZ and VPZ were significantly different (p=0.003 and p=0.001, respectively), Moreover, OPZ and VPZ were significantly different from each other (p=0.02). Compared to the control group, OPZ had significantly lower alpha diversity at week 12 (p=0.04), however, VPZ showed no diversity difference (p=0.2). When comparing taxonomic differences between the control and OPZ after 12 weeks of treatment, at the strain level, OPZ showed a decrease of Adlercreutzia caecimuris and Coriobacteriia bacterium and an increase of Bacteroidales bacterium; meanwhile at the species level, Adlercreutzia caecimuris decreased. After 12 weeks of VPZ treatment, on the strain level, Coriobacteriia bacterium and Turicibacter decreased and Prevotella and Bacteroidales bacterium increased compared to the control; meanwhile, at the family level Lactobacillaceae showed to be increased compared to the control at week 12. All taxonomic differences showed statistical significance (p=<0.001).
Conclusion
Long term treatment with OPZ or VPZ provoke significant changes in the gut's microbiota, each of them individually inducing a different set variation of the bacterial flora. Further studies investigating the impact of these variations may be warranted.
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