Journal Article

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

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

2025

Overview

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. Here, combining data from a clinical trial and animal models, the authors show a role for a gut-acylcarnitine axis in the development of salt-sensitive hypertension, and identify isovalerylcarnitine as a key microbiota-derived modulator and potential target for the precision prevention of hypertension.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 42/34 / 64/86 / 692/308/174 / 692/308/53/2423 / 692/4019/592/75/243 / 692/499 / 692/699/317 / 82/1 / 82/58 / 82/80 / Animal models / Animals / Biomarkers / Blood pressure / Blood Pressure - drug effects / Blood Pressure - physiology / Body mass index / Carnitine - analogs & derivatives / Carnitine - blood / Carnitine - metabolism / Cholesterol / Enzymes / Feces - microbiology / Female / Gastrointestinal Microbiome - drug effects / Gastrointestinal Microbiome - physiology / Genomes / Gut microbiota / High density lipoprotein / Humanities and Social Sciences / Humans / Hypertension / Hypertension - metabolism / Hypertension - microbiology / Intervention / Intestinal microflora / Male / Metabolites / Metabolome / Microbiota / Microorganisms / Middle Aged / multidisciplinary / Potassium / Rats / Risk management / Risk reduction / Salt / Salts / Science / Science (multidisciplinary) / Sensitivity / Shotguns / Sodium Chloride, Dietary - adverse effects / Variance analysis