心血管疾患における腸内マイクロバイオームの標的化：現在の治療戦略と将来の展望

The gut microbiota is increasingly recognized as an important modulator of cardiovascular health, demonstrating complicated interactions among diet, metabolism, immunology and host physiology. Evidence is accumulating that changes in the composition and function of the gut microbiome may contribute to the pathogenesis of atherosclerosis, hypertension, heart failure, thrombosis and other cardiovascular phenotypes through mechanisms involving microbial metabolites, intestinal barrier dysfunction, inflammation and metabolic dysregulation. In this context, the key question of this narrative review is: how far can modulation of the gut microbiome and its metabolic functions be a clinically meaningful approach in the prevention and treatment of cardiovascular disease, and which of the currently available microbiome-targeted approaches have sufficient mechanistic and clinical evidence to justify translation into cardiovascular practice? To answer this question, we review the evidence linking the gut microbiome to major cardiovascular phenotypes, such as atherosclerosis, hypertension, heart failure, thrombosis and atrial fibrillation, with particular focus on the mechanisms through which microbial metabolites, intestinal barrier dysfunction, inflammation and metabolic dysregulation may affect cardiovascular risk. We then review current and emerging strategies for microbiome modulation, including dietary interventions, prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation and targeted inhibition of microbial metabolic pathways such as trimethylamine (TMA)/trimethylamine -oxide (TMAO) production. We also examine bidirectional interactions between cardiovascular drugs and gut microbiome and the role of these interactions in the development of precision methods to cardiovascular prevention and treatment. Finally, we outline the major limitations of the current evidence and highlight goals for future mechanistic, translational and clinical research.