Gut Feeling: Microbiota as a Hidden Regulator of Hypertension

Emerging evidence identifies the gut microbiota as a key regulator of blood pressure (BP) through its role in metabolizing dietary substrates into bioactive compounds that influence vascular, immune, and neurohumoral pathways. This review synthesizes recent mechanistic, preclinical, and clinical evidence linking gut microbial dysbiosis to hypertension, with particular emphasis on nutrition-dependent microbial metabolism and its translational implications. Experimental studies demonstrate that depletion of short-chain fatty-acid (SCFA)-producing bacteria and enrichment of proinflammatory and trimethylamine-producing taxa contribute to endothelial dysfunction, immune activation, and renin-angiotensin-aldosterone system dysregulation. Fecal microbiota transplantation and germ-free animal models provide causal evidence that hypertensive microbiota can directly elevate BP. Human multiomics and metabolomic studies further show that microbial functional capacity and metabolite production, rather than taxonomic composition alone, are strongly associated with hypertensive phenotypes and therapeutic responsiveness. Importantly, dietary interventions, including high-fiber diets, resistant starch, and the Dietary Approaches to Stop Hypertension diet, modulate microbial composition and enhance SCFA production, providing a mechanistic basis for their antihypertensive effects. Microbiota-drug interactions have also emerged as a novel determinant of antihypertensive treatment efficacy. Collectively, these findings support a metabolite-centered framework in which diet-microbiota interactions influence BP regulation. Targeting the gut microbiota through nutritional and microbiome-based strategies represents a promising adjunctive approach for hypertension prevention and personalized management. However, large-scale longitudinal and interventional human studies are needed to establish causality and optimize microbiota-targeted therapies.