Hypertension: Microbiota-Targeting Treatment
Hypertension, the most prevalent cardiovascular disease (CVD), affects a significant portion of the global population. In 2015, it was estimated that approximately 1.13 billion people worldwide suffered from hypertension, with a prevalence exceeding 27.9% among Chinese adults aged over 18 years. Despite lifestyle modifications and medical interventions, a third of patients fail to achieve adequate control of their blood pressure (BP). Recent research has highlighted the role of the human gut microbiota in regulating immunity, inflammation, and metabolism. This has provided new insights into the mechanisms underlying hypertension, particularly through the influence of gut microbiota on blood lipid and glucose levels.
The gut microbiota has been found to monitor BP in various ways. Changes in BP are associated with alterations in the abundance or composition of gut microbiota. Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, exert direct effects on BP or indirect effects through various cytokines. Trimethylamine oxide has also been identified as an indicator of BP. Studies have demonstrated that probiotics, either used singly or in combination, can protect the heart against hypertension. Additionally, fecal microbiota transplantation (FMT) has shown potential in treating hypertension. This paper outlines the mechanisms linking hypertension and gut microbiota, discusses the use of probiotics in hypertension treatment, and explores the prospects of FMT as a novel therapeutic strategy beyond traditional antihypertensive drugs.
Probiotics, derived from traditional fermented foods and beneficial symbiotic biomass, have been shown to exert therapeutic effects on various diseases by restoring gut dysbiosis. Dysbiosis, or imbalance in gut microbiota, has been linked to an increased risk of hypertension. Although probiotics have not yet been widely adopted in clinical practice, their efficacy in treating CVDs, including hypertension, is a promising area of research.
SCFAs, produced by gut microbiota from indigestible polysaccharides, play a crucial role in regulating BP. These fatty acids are absorbed from the colon into the bloodstream, where they influence metabolic and inflammatory responses. For instance, propionate, when added to drinking water at a concentration of 200 mmol/L, significantly inhibits myocardial hypertrophy, fibrosis, vascular dysfunction, and hypertension in angiotensin II-infused wild-type Naval Medical Research Institute (NMRI) mice or apolipoprotein E gene knockout mice. BP reduction was observed in the late phase of angiotensin II infusion in wild-type NMRI mice, suggesting a beneficial effect of propionate on hypertension. Furthermore, kefir, a probiotic beverage, has been shown to prevent atherosclerosis and reduce BP in mice. Oral administration of kefir for nine weeks reduced mean arterial pressure and normalized heart rate in spontaneously hypertensive rats (SHRs). This reduction was attributed to decreased cardiac hypertrophy, improved cardiac contractility and calcium-handling proteins, and enhanced sympathetic activity mediated by the central nervous system.
Research on the relationship between Lactobacillus and hypertension has also yielded promising results. Lactobacillus fermentum CECT5716 (LC40) supplementation, while not directly inhibiting hypertension induced by NG-nitro-L-arginine methyl ester, has been shown to prevent gut microbiota imbalance, oxidative stress, vascular inflammation, T-helper type 17 (Th17)/regulatory T (Treg)-cell imbalance in mesenteric lymph nodes, and slightly improve endothelial cell function. Animal studies have demonstrated that probiotics can reverse pathological changes caused by gut microbiota disturbance, with similar findings observed in clinical trials. Probiotics have shown therapeutic efficacy in various metabolic diseases, including diabetes and hyperlipidemia, and their potential benefits in hypertension are increasingly recognized.
Meta-analyses have further supported the role of probiotics in reducing BP. A meta-analysis of 14 randomized placebo-controlled trials involving 702 participants found that probiotic fermented milk exerted antihypertensive effects in both pre-hypertensive and hypertensive patients, reducing systolic BP by 3.10 mmHg and diastolic BP by 1.09 mmHg. Another meta-analysis suggested that probiotic consumption may improve BP, particularly when baseline BP is elevated, multiple species of probiotics are consumed, the intervention duration is at least eight weeks, or the daily consumption dose is ≥1011 colony-forming units. However, some studies have reported contradictory results. For example, a clinical study found that the efficacy of probiotic yogurt or capsules containing Lactobacillus acidophilus La5 and Bifidobacterium animalis subsp. lactis BB-12 on BP was not significant, indicating that probiotics may not counter cardiovascular risk factors in all cases. This highlights the need for selective microbiota-based treatments for heart diseases and hypertension.
FMT, a core therapy for remodeling gut microbiota, has gained global attention in recent years. FMT has been used for various conditions, including Clostridium difficile infection, inflammatory bowel disease, neuron diseases, and metabolic diseases. Its potential in treating CVDs has been primarily investigated in animal models. In a mouse model of myocarditis, FMT led to an increase in microbial richness and diversity, as well as the Firmicutes/Bacteroidetes ratio. Treatment with fecal contents from untreated male mice reduced myocardial damage, inhibited inflammatory infiltration, balanced gut microbiota, and restored the number of Bacteroides and the composition of gut microbiota in experimental autoimmune myocarditis mice. In another study involving hypertensive mice, FMT from normotensive Wistar-Kyoto (WKY) rats to SHRs resulted in decreased basal systolic and diastolic BP, while FMT from SHRs to WKY rats increased BP. These findings suggest that FMT can modulate BP by altering gut microbiota composition.
Despite the promising results from animal studies, the application of FMT in clinical hypertension treatment remains limited. Future research should focus on conducting more clinical studies to validate the efficacy and safety of FMT. Standardization of the FMT process, such as the development of “washed microbiota transplantation,” is crucial to ensure its safe and effective use in clinical practice.
In conclusion, the gut microbiota plays a significant role in the development and progression of hypertension. Probiotics have shown potential in reducing BP and improving cardiovascular health, although their efficacy varies across studies. FMT, with its ability to modulate gut microbiota, holds promise as a novel therapeutic approach for hypertension. Further research is needed to fully understand the mechanisms underlying the gut microbiota-hypertension relationship and to develop effective microbiota-targeting treatments for hypertension.
doi.org/10.1097/CM9.0000000000000657
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