The potential of exercise-induced bile acid metabolism remodeling in cardiovascular protection

Abstract

Cardiovascular diseases (CVDs) persist as a predominant global health burden, necessitating the refinement of accessible preventive strategies beyond conventional pharmacotherapy. While physical exercise is universally acknowledged as a cornerstone of cardiovascular prevention, its precise molecular mechanisms extend beyond direct hemodynamic improvements to encompass systemic metabolic remodeling. This review synthesizes emerging evidence delineating the exercise-BA axis as a critical, yet historically underappreciated, mediator of cardioprotection. We first elucidate the physiological nuances of BA homeostasis, highlighting the intricate interplay between hepatic synthesis, microbial biotransformation, and enterohepatic circulation. Subsequently, we examine how exercise induces specific shifts in the circulating BA pool and gut microbial composition, thereby modulating the signaling capacity of key receptors, including the farnesoid X receptor (FXR) and takeda G protein-coupled receptor (TGR5). These exercise-induced metabolic adaptations confer cardiovascular benefits by mitigating atherosclerotic progression, regulating blood pressure through vascular and renal mechanisms, preserving myocardial function in heart failure, and ameliorating diabetic cardiomyopathy (DbCM). Finally, we identify critical knowledge gaps and propose future research directions aimed at translating these insights into novel clinical strategies for CVD management. The potential of exercise-induced BA metabolism remodeling in cardiovascular protection