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<p>This study aims to investigate the roles of gut microbiota and plasma metabolites in salt sensitivity (SS) of blood pressure (SSBP) and hypertension. A 23-day, multicenter, dietary salt intervention trial (the MetaSalt study) recruited 528 participants who underwent a baseline observation, low-salt, and high-salt interventions. SSBP was assessed and used as the primary outcome, and fecal shotgun metagenome and plasma targeted metabolome were measured. We found that high salt significantly altered 85 gut-microbial species (<i>p</i> &lt; 9.42 × 10<sup>−5</sup>) and 70 metabolites (<i>p</i> &lt; 2.26 × 10<sup>−4</sup>). Among them, the changes in 22 species and 8 metabolites were associated with SSBP (<i>p</i> &lt; 0.05), and a gut microbiota-acylcarnitine network implicated in SSBP was identified, with a gut microbiota-derived metabolite, isovalerylcarnitine, as the core metabolite. Isovalerylcarnitine was also inversely associated with SSBP in the GenSalt study (<i>p</i> = 0.0102). Importantly, increased isovalerylcarnitine attenuated SS hypertension and improved endothelial function in rats, and was associated with reduced risk (ranging from 13% to 19%) of BP progression and incident hypertension in a prospective cohort (n = 3907, median follow-up = 5.5 years). This study demonstrated that the gut-acylcarnitine axis may play roles in the development of SS hypertension. Trial number: ChiCTR1900025171.</p>

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Gut microbiota-derived metabolite isovalerylcarnitine modulates salt sensitivity of blood pressure and incident hypertension: a multicenter dietary salt intervention trial

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月26日

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  • Zhennan Lin,
  • Shujie Li,
  • Mengyao Liu,
  • Jianxin Li,
  • Fangchao Liu,
  • Jie Cao,
  • Shufeng Chen,
  • Keyong Huang,
  • Yaqin Wang,
  • Hongfan Li,
  • Yan Wang,
  • Bin Yang,
  • Dongmei Xing,
  • Qing Wang,
  • Xu Ji,
  • Xingqiang Bai,
  • Dongsheng Hu,
  • Ming Zhang,
  • Dongshuang Guo,
  • Jianfeng Huang,
  • Bin Geng,
  • Dongfeng Gu,
  • Xiangfeng Lu

摘要

This study aims to investigate the roles of gut microbiota and plasma metabolites in salt sensitivity (SS) of blood pressure (SSBP) and hypertension. A 23-day, multicenter, dietary salt intervention trial (the MetaSalt study) recruited 528 participants who underwent a baseline observation, low-salt, and high-salt interventions. SSBP was assessed and used as the primary outcome, and fecal shotgun metagenome and plasma targeted metabolome were measured. We found that high salt significantly altered 85 gut-microbial species (p < 9.42 × 10−5) and 70 metabolites (p < 2.26 × 10−4). Among them, the changes in 22 species and 8 metabolites were associated with SSBP (p < 0.05), and a gut microbiota-acylcarnitine network implicated in SSBP was identified, with a gut microbiota-derived metabolite, isovalerylcarnitine, as the core metabolite. Isovalerylcarnitine was also inversely associated with SSBP in the GenSalt study (p = 0.0102). Importantly, increased isovalerylcarnitine attenuated SS hypertension and improved endothelial function in rats, and was associated with reduced risk (ranging from 13% to 19%) of BP progression and incident hypertension in a prospective cohort (n = 3907, median follow-up = 5.5 years). This study demonstrated that the gut-acylcarnitine axis may play roles in the development of SS hypertension. Trial number: ChiCTR1900025171.