Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Key Laboratory of Gut Microbiota Translational Medicine Research, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
J Gastroenterol Hepatol. 2022 Oct;37(10):1935-1945. doi: 10.1111/jgh.15973. Epub 2022 Aug 22.
The influence of gastric acid inhibitors (GAIs) on nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy is controversial. Herein, the influences of different GAIs on NSAID-induced intestinal injury and the underlying mechanisms are clarified.
Indomethacin (IND; 10 mg/kg/day) was administered to mice to induce small intestinal injury. Disease activity was examined macroscopically and histologically. The permeability of small intestine was evaluated by measuring plasma lipopolysaccharide levels. 16S rDNA sequencing was performed to determine the composition of intestinal flora.
Among the four GAIs, ilaprazole (IPZ) significantly attenuated IND-induced small intestinal injury and maintained the integrity of the mucosal barrier. Omeprazole (OPZ) and vonoprazan (VPZ) ameliorated ulceration without significant differences, while rabeprazole (RPZ) failed to protect against the injury. To explore the potential mechanism, we investigated changes in the gut microbiota mediated by GAIs. After 5-day administration, GAIs significantly altered the composition of the gut microbiota. The IND group had a significant decrease in alpha diversity compared with the control group, and this decrease was reversed by OPZ and IPZ treatment, respectively. After IPZ treatment, the community membership was more assembled in the control group than the IND group. Further, we found that Lactobacillus was significantly increased in the groups of OPZ, IPZ, and VPZ, while Bacteroides was significantly increased in the RPZ group.
Our results indicated that GAIs have different influences on the mucosal barrier, possibly by altering the composition of intestinal microbiota, and the impacts mediated by various GAIs in the IND-induced intestinal damage model seem different.
胃酸抑制剂（GAIs）对非甾体抗炎药（NSAID）诱导的肠病的影响存在争议。本文旨在阐明不同 GAIs 对 NSAID 诱导的肠道损伤的影响及其潜在机制。
采用吲哚美辛（IND；10mg/kg/天）灌胃诱导小鼠小肠损伤模型，宏观和组织学检查评估疾病活动度，检测血浆内毒素水平评估小肠通透性，16S rDNA 测序分析肠道菌群组成。
在四种 GAIs 中，艾普拉唑（IPZ）可显著减轻 IND 诱导的小肠损伤，维持黏膜屏障的完整性。奥美拉唑（OPZ）和沃诺拉赞（VPZ）可改善溃疡，但无显著差异，而雷贝拉唑（RPZ）则不能保护肠损伤。为了探究潜在机制，我们研究了 GAIs 介导的肠道菌群变化。GAIs 给药 5 天后，肠道菌群组成发生显著改变。与对照组相比，IND 组的 alpha 多样性显著降低，OPZ 和 IPZ 处理分别逆转了这一下调。IPZ 处理后，控制组的群落组成比 IND 组更具聚集性。进一步发现，OPZ、IPZ 和 VPZ 组的乳杆菌显著增加，而 RPZ 组的拟杆菌显著增加。
我们的研究结果表明，GAIs 对黏膜屏障具有不同的影响，可能通过改变肠道菌群的组成，而不同 GAIs 介导的 IND 诱导的肠道损伤模型中的影响似乎不同。
