Chen Chen, Liang Huizhu, He Meibo, Duan Ruqiao, Guan Yu, Wang Fangfang, Duan Liping
Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China.
Department of Cardiology, Peking University People's Hospital, Beijing 100044, China.
Chin Med J (Engl). 2024 Sep 23;138(5):542-52. doi: 10.1097/CM9.0000000000003148.
Several randomized controlled studies have suggested that the prophylactic use of proton pump inhibitors (PPIs) in intensive care unit (ICU) patients could not reduce the incidence of gastrointestinal bleeding (GIB) and may increase adverse events such as intestinal infection and pneumonia. Gut microbiota may play a critical role in the process. PPIs has been widely prescribed for GIB prophylaxis in patients with acute coronary syndrome (ACS). This study aimed to determine the short-term effects of PPI and histamine-2 receptor antagonist (H2RA) treatment on gut microbiota of ACS patients.
The study was designed as a single-blind, multicenter, three-parallel-arm, randomized controlled trial conducted at three centers in Beijing, China. We enrolled ACS patients at low-to-medium risk of GIB and randomized (2:2:1) them to either PPI (n = 40), H2RA (n = 31), or control group (n = 21). The primary outcomes were the alterations in gut microbiota after 7 days of acid suppressant therapy. Stool samples were collected at baseline and 7 days and analyzed by 16S rRNA gene sequencing.
There were no significant changes in the diversity of gut microbiota after the short-term use of acid suppressants, but the abundance of Fusobacterium significantly increased and that of Bifidobacterium significantly decreased, especially in PPI users. In addition, the abundance of some pathogenic bacteria, including Enterococcus and Desulfovibrio, was significantly elevated in the PPI users. The fecal microbiota of the PPI users included more arachidonic acid metabolism than that of control group.
PPIs may increase the risk of infection by adversely altering gut microbiota and elevating arachidonic acid metabolism, which may produce multiple proinflammatory mediators. For ACS patients at low-to-medium risk of GIB, sufficient caution should be paid when acid-suppressant drugs are prescribed, especially PPIs.
www.chictr.org.cn/ (ChiCTR2000029552).
多项随机对照研究表明，在重症监护病房（ICU）患者中预防性使用质子泵抑制剂（PPI）并不能降低胃肠道出血（GIB）的发生率，反而可能增加肠道感染和肺炎等不良事件的发生风险。肠道微生物群可能在此过程中起关键作用。PPI已被广泛用于急性冠状动脉综合征（ACS）患者的GIB预防。本研究旨在确定PPI和组胺2受体拮抗剂（H2RA）治疗对ACS患者肠道微生物群的短期影响。
本研究设计为一项单盲、多中心、三平行组、随机对照试验，在中国北京的三个中心进行。我们纳入了GIB低至中度风险的ACS患者，并将他们随机（2:2:1）分为PPI组（n = 40）、H2RA组（n = 31）或对照组（n = 21）。主要结局是抑酸治疗7天后肠道微生物群的变化。在基线和第7天采集粪便样本，并通过16S rRNA基因测序进行分析。
短期使用抑酸剂后，肠道微生物群的多样性没有显著变化，但梭杆菌属的丰度显著增加，双歧杆菌属的丰度显著降低，尤其是在使用PPI的患者中。此外，在使用PPI的患者中，包括肠球菌属和脱硫弧菌属在内的一些病原菌的丰度显著升高。使用PPI的患者的粪便微生物群比对照组含有更多的花生四烯酸代谢产物。
PPI可能通过不利地改变肠道微生物群和提高花生四烯酸代谢来增加感染风险，这可能产生多种促炎介质。对于GIB低至中度风险的ACS患者，在开具抑酸药物时应格外谨慎，尤其是PPI。
