The Protective Role of Gut Microbiota Metabolites in Cardiovascular Disease

Abstract

Cardiovascular disease (CVD) continues to rank among the primary drivers of human mortality, creating an urgent requirement for multifaceted prevention and clinical intervention plans. Apart from conventional medications, surgical operations, and, interventional therapies, therapeutic strategies centered on gut microbiota and its metabolites have exhibited outstanding translational prospects for CVD management in recent decades. The present review explores the intrinsic mechanisms through which gut microbial metabolites exert cardioprotective impacts, aiming to systematically interpret their functional pathways. Key biologically active compounds synthesized by intestinal microbiota include short-chain fatty acids (SCFAs), secondary bile acids, amino acids, and relevant metabolites like indole-3-propionic acid, hydrogen sulfide, and polyamines. Numerous studies confirm these microbial metabolites exert combined cardiac protection through distinct biological pathways. SCFAs lower blood pressure, improve metabolism and protect endothelium by activating GPR41/GPR43. Secondary bile acids regulate lipid metabolism and inflammation primarily through farnesoid X receptor (FXR) and G protein-coupled receptor TGR5 signaling. Meanwhile, indole-3-propionic acid, hydrogen sulfide, and polyamines boost myocardial contraction, alleviate oxidative injury and retard myocardial fibrosis. Clinical data indicate endogenous levels of these metabolites closely relate to risks of atherosclerosis, acute coronary syndrome and stroke. Collectively, gut microbial metabolites provide critical cardioprotection across all CVD pathological stages via immune regulation, metabolic balance, endothelial protection, and anti-fibrosis effects. This review puts forward innovative research perspectives and potential therapeutic targets for the prevention and clinical treatment of cardiometabolic disorders.