# Gut microbiota–derived polyamine pathways associated with mean blood pressure

**Authors:** Yasuo Ikagawa, Shigefumi Okamoto, Kouki Taniguchi, Ren Mizoguchi, Atsushi Hashimoto, Rikako Imamura, Hiroshi Arakawa, Kohei Ogura, Masashi Yanagihara, Hiromasa Tsujiguchi, Akinori Hara, Hiroyuki Nakamura, Kazuyoshi Hosomichi, Shigehiro Karashima

PMC · DOI: 10.1038/s41440-025-02490-8 · Hypertension Research · 2025-12-18

## TL;DR

This study explores how gut microbiota and polyamine metabolism may influence blood pressure, especially in relation to salt sensitivity.

## Contribution

The study identifies specific gut microbial metabolic traits linked to blood pressure regulation and salt sensitivity.

## Key findings

- Salt-sensitive and non-salt-sensitive hypertensive groups showed significant differences in gut microbiota α-diversity.
- Normotensive individuals had higher levels of spermidine synthase, a key antihypertensive enzyme, regardless of salt intake.
- Bacterial species with polyamine metabolic genes varied significantly between groups, indicating group-specific traits.

## Abstract

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.

## Linked entities

- **Chemicals:** sodium chloride (PubChem CID 5234), spermidine (PubChem CID 1102)

## Full-text entities

- **Genes:** SRM (spermidine synthase) [NCBI Gene 6723] {aka PAPT, SPDSY, SPS1, SRML1}
- **Diseases:** Hypertension (MESH:D006973)
- **Chemicals:** spermidine (MESH:D013095), arginine (MESH:D001120), NaCl (MESH:D012965), polyamine (MESH:D011073), salt (MESH:D012492)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12960250/full.md

## References

1 references — full list in the complete paper: https://tomesphere.com/paper/PMC12960250/full.md

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Source: https://tomesphere.com/paper/PMC12960250