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

Abstract

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 effect of probiotics is insufficiently understood. Herein, we investigated the antihypertensive effect of 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 significantly 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 affect 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. Elevated blood pressure affects 40% of the adult population, which accounts for high cardiovascular disease risk and further high mortality yearly. The global understanding of the gut microbiome for hypertension may provide important insights into the prevention. Bifidobacterium lactis M8 and Lactobacillus rhamnosus M9 originated from human breast milk, were able to decrease blood pressure, and modified metabolites in a high fructose-induced elevated blood pressure mouse model. Moreover, we found there was a close relationship between unexplored gut microbes and elevated blood pressure. Also, subsequently, the cross-link was explored among gut microbes, metabolites, and some metabolic pathways in gut microbial environment through introducing novel prediction methodology and bioinformatic analysis. It allowed us to hypothesize that probiotics can prevent elevated blood pressure via gut microbiota and related metabolism.Thus, utilization of dietary strategies (such as probiotics) to maintain the blood pressure level is of crucial importance.

Evidence from mendelian randomization identifies several causal relationships between primary membranous nephropathy and gut microbiota

“…Ongoing research indicates a disrupted ecological balance of Alistipes , which can prove advantageous or detrimental. Specifically, Alistipes proved to be beneficial in investigations concerning liver fibrosis, cancer immunotherapy, and cardiovascular disease [ 24–26 ]. On the other hand, previous findings have demonstrated the association of Alistipes with depression and its pathogenic role in colorectal cancer [ 27 , 28 ].…”

The Networked Interaction between Probiotics and Intestine in Health and Disease: A Promising Success Story

“…Streptococcus thermophilus is commonly used in combination with other probiotics or as a starter culture in dairy fermentation. It has been studied for its potential health benefits [ 58 , 62 , 75 ]. E. coli Nissle 1917 is a specific strain of Escherichia coli which has demonstrated probiotic properties and has been studied for its efficacy in treating various gut disorders [ 63 , 64 ] ( Table 3 ).…”

Microbial influence on blood pressure: unraveling the complex relationship for health insights

“…For instance, a study discovered that raised BP was linked to the prevalence of Firmicutes and Bacteroidetes in gut by using several hypertension models, including rats that were spontaneously hypertensive and Dahl salt-sensitive [35] . Numerous large-cohort investigations have revealed inconsistent microbiological indicators, and the connection between GM and hypertension still has to be clarified [36] . However, some studies have identified specific microbes and metabolic pathways that may help explain the protective effect of probiotics (live microorganisms, typically bacteria or yeast, that confer health benefits) in treating hypertension; in fact, the metagenomic analysis revealed that the increased Lawsonia and Pyrolobus, and reduced Alistipes and Alloprevotella levels were tightly correlated with lowered BP, suggesting that these bacteria could affect BP by changing steroid hormone levels [37] .…”

“…Global knowledge about the gut microbiome’s role in hypertension may offer crucial insights into its prevention. Recently, it was demonstrated that the human breast milk-derived bacteria, administered orally, could lower BP and alter metabolites in a mouse model of elevated BP induced by high fructose, suggesting a potential therapeutic approach [ 37 ] .…”

“…Probiotic supplements dramatically lowered systolic and diastolic BP, according to other studies [ 72 ] , notably in individuals with hypertension and type 2 diabetes. In addition, it has been discovered that two probiotic strains, Lactobacillus rhamnosus and Bifidobacterium lactis , which are found in foods like cheese and yogurt, may help decrease BP [ 37 ] . Utilizing both probiotics and prebiotics together offers a synergistic approach to optimally modify GM and potentially exert greater BP-reducing effects than either alone.…”