The gut-heart dialogue: an epigenetic perspective on myocardial infarction

Myocardial infarction (MI) remains a leading cause of global mortality, with adverse cardiac remodeling and heart failure presenting persistent metabolic and clinical challenges. While traditional pharmacotherapies have improved outcomes, there is an urgent need to elucidate how lifestyle and nutritional factors influence disease progression. Emerging evidence underscores the critical interplay between natural bioactive compounds (e.g., dietary fibers, polyphenols), the gut microbiota, and host metabolic regulation. This review systematically clarifies the “gut microbiota-epigenetic axis” as a pivotal mechanism linking nature-derived bioactives to cardiac repair. We delineate how the gut microbiota transforms specific bioactives into functional metabolites, such as short-chain fatty acids (SCFAs) from fibers and urolithin A from ellagitannins, which act as potent epigenetic modulators. These microbial metabolites remodel the epigenetic landscape of the host heart via histone modification and DNA methylation, thereby regulating gene networks governing inflammation, energy metabolism, and fibrosis. Synthesizing evidence from in vivo animal studies and clinical observations, we explore therapeutic strategies centered on natural bioactives, including high-fiber dietary interventions and polyphenol supplementation, alongside probiotics and postbiotics. By integrating the metabolic potential of the gut microbiome with epigenetic regulation, this review offers novel insights into how natural bioactive compounds can be leveraged for precision prevention and therapeutic strategies in myocardial infarction.