Gut microbiota–derived polyamine pathways associated with mean blood pressure

Hypertension is a common lifestyle-related disease and is influenced by various factors, including excessive salt intake. Recently, the gut microbiota (GM) has gained attention for its potential involvement in blood pressure regulation; however, polyamine metabolism involvement remains poorly understood. Sixty participants aged ≥40 years from Shika Town, Japan, were stratified into four groups (n = 15 each) based on mean blood pressure and urinary sodium chloride (u-NaCl) excretion. The clinical parameters were evaluated, and fecal samples were analyzed using shotgun metagenomic sequencing to assess the microbial composition and abundance of genes related to arginine-polyamine metabolism. Three major findings were observed: (1) Significant differences in the α-diversity of GM were observed between salt-sensitive and non-salt-sensitive hypertensive groups; (2) The abundance of spermidine synthase (EC 2.5.1.16), a key enzyme in polyamine metabolism with known antihypertensive effects, was significantly higher in normotensive individuals, independent of u-NaCl excretion; and (3) Bacterial species harboring polyamine metabolic enzyme genes, including EC 2.5.1.16, differed significantly between groups, suggesting group-specific microbial metabolic traits. These findings suggest that GM-mediated polyamine metabolism may contribute to the regulation of salt-sensitive blood pressure. While variations in spermidine-producing bacteria and the involvement of EC 2.5.1.16 were observed, these factors alone do not fully account for the intergroup differences related to salt intake. Thus, polyamine metabolism likely plays a part in salt sensitivity, but additional microbial and host factors are also involved. Further studies are needed to validate these findings and to explore microbiota-targeted strategies for the prevention and treatment of hypertension.