Host-microbiota interactions regulate gut serotonergic signaling: implications for hypertension

Serotonin (5-hydroxytryptamine, 5-HT) is a highly conserved signaling molecule present across diverse taxa, including plants, invertebrates, and vertebrates. In mammals, the majority of peripheral serotonin is synthesized in the gastrointestinal tract by enteric neurons and enterochromaffin cells via tryptophan hydroxylases. Its biosynthesis and release are influenced by dietary components and microbial metabolites, particularly short-chain fatty acids produced by the gut microbiota. Once released into the periphery, serotonin exerts pleiotropic effects, regulating intestinal motility and secretion, modulating vascular tone, and influencing blood pressure through both direct actions and vagal sensory pathways engaging central and autonomic circuits. Dysregulation of colonic serotonin production or signaling has been implicated in metabolic, neuropsychiatric, and cardiovascular disorders, including postprandial blood pressure abnormalities and hypertension. Emerging evidence highlights a bidirectional relationship between gut microbes and host serotonergic pathways, suggesting that microbiota-targeted interventions may hold therapeutic potential for cardiometabolic regulation. Advancing our understanding of gut serotonergic signaling, particularly the interplay between host and microbial factors, could inform the development of innovative strategies to treat hypertension and related conditions.