Impact of short-term proton pump inhibitors vs. histamine-2 receptor antagonists on gut microbiota in patients with acute coronary syndrome: A multicenter randomized trial

Chen Chen; Huizhu Liang; Meibo He; Ruqiao Duan; Yu Guan; Fangfang Wang; Liping Duan

doi:10.1097/CM9.0000000000003148

Impact of short-term proton pump inhibitors vs. histamine-2 receptor antagonists on gut microbiota in patients with acute coronary syndrome: A multicenter randomized trial

Chin Med J (Engl). 2024 Sep 23. doi: 10.1097/CM9.0000000000003148. Online ahead of print.

Authors

Chen Chen¹, Huizhu Liang², Meibo He³, Ruqiao Duan¹, Yu Guan⁴, Fangfang Wang⁵, Liping Duan¹

Affiliations

¹ Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China.
² Department of Cardiology, Peking University People's Hospital, Beijing 100044, China.
³ Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
⁴ Department of Cardiology, Beijing Haidian Hospital, Beijing 100080, China.
⁵ Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing 100191, China.

PMID: 39307932
DOI: 10.1097/CM9.0000000000003148

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Registration: www.chictr.org.cn/ (ChiCTR2000029552).