Probiotics Bifidobacterium lactis M8 and Lactobacillus rhamnosus M9 prevent high blood pressure via modulating the gut microbiota composition and host metabolic products

High-fructose intake is one of the high-risk factors for hypertension. Several probiotics have been reported to reduce high blood pressure (BP) via modulating gut microbiota, but the mechanism of the antihypertensive effecteffect of probiotics is insufficientlyciently understood. Herein, we investigated the antihypertensive effecteffect of Bifidobacte-Bifidobacterium lactis M8 and Lactobacillus rhamnosus M9 based on the integrative analysis of gut metagenome and serum metabolome in high-fructose-treated mice. After 16-week intervention, M8 and M9 significantlysignificantly reduced the median blood pressure by 16.92% and 15.39% in SBP, and 18.56% and 20.62% in DBP, respectively. Metagenomic analysis revealed that the increased Lawsonia and Pyrolobus, and reduced Alistipes and Alloprevotella levels were tightly correlated with lowered BP. Functionally, the decreased pathways of "base excision repair" (BER) and "D-glutamine and D-glutamate metabolism" were associated with BP reduction. Metabolomics data analysis further revealed that the probiotic interventions regulated vascular smooth muscle contraction, serotonergic synapse, cholinergic synapse, and lipid and vitamin metabolism in BP control. Additionally, association analyses indicated a strong negative correlation between Alistipes and "steroid hormone biosynthesis," suggesting that Alistipes could affectaffect blood pressure by changing steroid hormone levels. In conclusion, our findings indicate that the probiotic efficacies in alleviating hypertension are linked to specific gut microbes and metabolic pathways, which provide a potential mechanistic understanding of probiotics modulated blood pressure, paving the way for future assessment of the therapeutic potential of probiotics in hypertension management.