Prophylactic Supplementation with Lactobacillus Reuteri or Its Metabolite GABA Protects Against Acute Ischemic Cardiac Injury

• Published in: Advanced science Vol. 11; no. 18; pp. e2307233 - n/a
• Main Authors: Wang, Jiawan, Zhang, Hao, Yuan, Hailong, Chen, Siqi, Yu, Ying, Zhang, Xuan, Gao, Zeyu, Du, Heng, Li, Weitao, Wang, Yaohui, Xia, Pengyan, Wang, Jun, Song, Moshi
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01-05-2024; John Wiley and Sons Inc; Wiley
• Subjects: acute ischemic cardiac injury; Animals; Antibiotics; Cardiac function; Cardiovascular disease; Coronary vessels; Disease Models, Animal; Disease prevention; Ejection fraction; GABA; gamma-Aminobutyric Acid - metabolism; Gastrointestinal Microbiome; Heart attacks; Heart failure; Inflammation; Ischemia; Lactobacillus reuteri; Limosilactobacillus reuteri - metabolism; Macrophages - metabolism; Male; Metabolism; Metabolites; Mice; Mice, Inbred C57BL; Microbiota; microbiota‐derived metabolite; Myocardial Ischemia - metabolism; Myocardial Ischemia - prevention & control; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - prevention & control; Probiotics; Probiotics - administration & dosage; Probiotics - therapeutic use; prophylactic supplementation; Student's t-test; GABA; Lactobacillus reuteri; acute ischemic cardiac injury; prophylactic supplementation; microbiota‐derived metabolite
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202307233

The gut microbiome has emerged as a potential target for the treatment of cardiovascular disease. Ischemia/reperfusion (I/R) after myocardial infarction is a serious complication and whether certain gut bacteria can serve as a treatment option remains unclear. Lactobacillus reuteri (L. reuteri) is a well‐studied probiotic that can colonize mammals including humans with known cholesterol‐lowering properties and anti‐inflammatory effects. Here, the prophylactic cardioprotective effects of L. reuteri or its metabolite γ‐aminobutyric acid (GABA) against acute ischemic cardiac injury caused by I/R surgery are demonstrated. The prophylactic gavage of L. reuteri or GABA confers cardioprotection mainly by suppressing cardiac inflammation upon I/R. Mechanistically, GABA gavage results in a decreased number of proinflammatory macrophages in I/R hearts and GABA gavage no longer confers any cardioprotection in I/R hearts upon the clearance of macrophages. In vitro studies with LPS‐stimulated bone marrow‐derived macrophages (BMDM) further reveal that GABA inhibits the polarization of macrophages toward the proinflammatory M1 phenotype by inhibiting lysosomal leakage and NLRP3 inflammasome activation. Together, this study demonstrates that the prophylactic oral administration of L. reuteri or its metabolite GABA attenuates macrophage‐mediated cardiac inflammation and therefore alleviates cardiac dysfunction after I/R, thus providing a new prophylactic strategy to mitigate acute ischemic cardiac injury.
The gut microbiome has emerged as a potential target for the treatment of cardiovascular disease. It is found that the prophylactic oral administration of Lactobacillus reuteri or its metabolite GABA attenuates macrophage‐mediated cardiac inflammation and therefore alleviates cardiac dysfunction after myocardial ischemia reperfusion, thus providing a new prophylactic strategy to mitigate acute ischemic cardiac injury.