Long-term Effects of Potassium-competitive Acid Blockers and Proton Pump Inhibitors on Gastrin, Gastric Emptying Rate, and Small Intestinal Microbiota in Rats.

Background/aims: Proton pump inhibitors (PPIs) are widely used for gastric acid suppression but are associated with adverse effects such as hypergastrinemia and delayed gastric emptying (GE). Potassium-competitive acid blockers (P-CABs), a new class of acid suppressants, rapidly and sustainably inhibit gastric acid secretion. We compared the long-term effects of different P-CABs and PPIs on gastric pH, serum gastrin levels, GE, and small intestinal microbiota in a rat model.

Methods: Seventy-two male Sprague-Dawley rats were assigned to receive control, esomeprazole, tegoprazan, or vonoprazan by oral gavage for 1, 2, or 4 weeks. After sacrifice, gastric pH, serum gastrin levels, and GE were measured, and the small intestinal microbiota were analyzed using 16S ribosomal RNA sequencing.

Results: All drug-treated groups exhibited significantly higher gastric pH than the control group. Tegoprazan achieved the highest pH at week 2, surpassing those of esomeprazole and vonoprazan. Serum gastrin levels were significantly elevated in all drug-treated groups but remained stable from weeks 1 to 4, indicating a plateau effect. GE was transiently delayed at week 2 but returned to baseline by week 4 in all drug-treated groups. Long-term administration of both P-CABs and PPI led to reduced microbial diversity and distinct taxonomic shifts with changes in the abundance of Prevotella and Acetatifactor in the small intestine. However, with prolonged administration, these differences in microbiota composition gradually diminished.

Conclusions: Long-term administration of P-CABs and PPIs altered gastrin levels, GE, and gut microbiota. Therefore, the acid suppression-related adverse effects of P-CABs and PPIs are expected to be similar.