Choi Hyun Seok, Kim Min Seob, Yu Myeong Hwan, You Jisong, Seon Dahyun, Ko Gwangpyo, Unno Tatsuya, Lee Moon Young, Kim Yong Sung
Department of Physiology, Wonkwang University School of Medicine, Iksan, Jeollabuk-do, Korea.
Digestive Disease Research Institute, Wonkwang University School of Medicine, Iksan, Jeollabuk-do, Korea.
J Neurogastroenterol Motil. 2025 Jul 30;31(3):384-395. doi: 10.5056/jnm25024.
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.
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.
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 and in the small intestine. However, with prolonged administration, these differences in microbiota composition gradually diminished.
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.
背景/目的：质子泵抑制剂（PPIs）被广泛用于抑制胃酸分泌，但会引发如高胃泌素血症和胃排空延迟（GE）等不良反应。钾离子竞争性酸阻滞剂（P-CABs）作为一类新型的抑酸剂，能快速且持续地抑制胃酸分泌。我们在大鼠模型中比较了不同P-CABs和PPIs对胃pH值、血清胃泌素水平、胃排空及小肠微生物群的长期影响。
72只雄性Sprague-Dawley大鼠被分为对照组、埃索美拉唑组、替戈拉赞组或沃克索拉唑组，通过灌胃给药1、2或4周。处死大鼠后，测量胃pH值、血清胃泌素水平和胃排空情况，并使用16S核糖体RNA测序分析小肠微生物群。
所有药物治疗组的胃pH值均显著高于对照组。替戈拉赞在第2周时达到最高pH值，超过了埃索美拉唑和沃克索拉唑。所有药物治疗组的血清胃泌素水平均显著升高，但从第1周到第4周保持稳定，表明存在平台效应。所有药物治疗组的胃排空在第2周时短暂延迟，但在第4周时恢复到基线水平。长期给予P-CABs和PPI均导致微生物多样性降低，以及小肠中特定分类群的丰度变化和明显的分类学转变。然而，随着给药时间延长，这些微生物群组成的差异逐渐减小。
长期给予P-CABs和PPIs会改变胃泌素水平、胃排空和肠道微生物群。因此，预计P-CABs和PPIs与抑酸相关的不良反应相似。
