Use of Probiotics in the Management of Hypertension - Exploring the Potential
Hypertension has become a common chronic medical condition affecting > 20% of adult population worldwide. It is certainly established to be a major contributing factor for increasing complications of metabolic syndrome by adding one or more comorbidities such as heart disease, stroke, chronic renal failure, myocardial infarction, blindness, and dementia. It is also known that hypertension is also often considered as a lifestyle disorder, and clinically classified as primary (essential) and secondary. Essential hypertension remains a major cause in about 90% - 95% of all cases of hypertension and it is believed to be caused due to genetic factors and nonspecific lifestyle, with exact aetiology and pathophysiology remains an opportunity yet to be fully defined. (1)
While by 2025, the total number of hypertensive patients is expected to increase to 1.56 billion globally (2) , emerging evidence is bringing out the important role of microbiota in hypertension and its treatment with probiotics. We review the spectrum of evidence reflecting the interplay of gut microbiota in the context of high blood pressure, hypertension associated co-morbidities and potential of probiotics in the therapeutic armamentarium of hypertension.
Gut Microbiota Interplay in Health & Hypertension
In a normal individual, the Firmicutes/ Bacteroidetes (F/B) ratio evolves across different phases of life. (3) In infants, adults, and elderly, the observed values of F/B ratio are around 0.4, 10.9, and 0.6, respectively (4). In a healthy person, the balanced F/B ratio helps to maintain the acetate-butyrate production, (5) and fermentation of carbohydrates, thus synthesizing volatile fatty acids as an energy source to host. (3) Numerable such functional roles have been attributed to balanced F/B ratio.
It has been reported that in hypertension, the patterns of microbial richness, diversity, and evenness decreased significantly, while the F/B ratio increases. Such evidence is in alignment with human data, and a similar pattern of Dysbiosis has been reported. Similar changes in gut microbiota were observed in the chronic angiotensin II infusion animal model, most notably decreased microbial richness and an increased F/B ratio. Interestingly, the F/B ratio increases in coronary artery disease patients.(6) And also altered in adiposity, obesity, diabetes, metabolic syndrome - all cardio-metabolic co-morbidities often coexist with hypertension in the real world. Therefore, there are huge chances that this ratio may also have altered significantly in the case of hypertension, as it is one of the cardio-metabolic disorders sharing many common etiological factors with these diseases and thereby disturbing normal gut flora, leading to the development and progression of hypertension to chronic threatening complications. (2)
Potential Therapeutic Role of Probiotics
To exert good pharmacotherapeutic action, probiotics need to possess certain characteristics as they need to be acid and bile resistant, metabolically active in the gut, able to adhere to the digestive tract lining, possess antimicrobial activity towards pathogenic bacteria; and reduce colon pH. (7). For therapeutic use, the most studied probiotics in hypertension include Enterococcus faecium, Bifidobacterium infantis, Bifidobacterium animalis lactis, Saccharomyces cerevisiae, Streptococcus thermophilus, and Lactobacillus (Lactobacillus helveticus, Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei, and Lactobacillus plantarum), while others are Lactobacillus GG, Bifidobacterium lactis Bb12, Saccharomyces boulardii, Lactobacillus agilis, and yeast Saccharomyces boulardii. (8)
Probiotics - Plausible Nitric Oxide Producing Action
Evidence indicates that in vascular smooth muscle cells, probiotic intake has been shown to increase intracellular calcium (Ca 2+ ) in endothelial cells to produce nitric oxide (NO) which ultimately causes vasodilatation and prevents the contractility of blood vessels, thus indicating its potential role in hypertension through its action on the vascular wall (9)
Probiotics in Hypertension – Overview of Action 1 & Evidence
The following gut and beyond gut actions of probiotics may be responsible for its positive influence in improving hypertension and hypertension associated risk factors, which are often culprits in sustaining the high blood pressure:
• Decrease gut permeability, toxemia and systemic inflammation
• Balancing Na + and energy metabolism
• F/B ratio and Ca 2+ homeostasis
• Vascular Dilatation
• Inhibiting fat accumulation in adipose tissue
• Decrease insulin resistance and obesity
A metaanalysis of nine randomized trials demonstrated a significant decrease in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with hypertension. A synergistic effect has been observed when multiple species of probiotics were administered. The interpretation drawn from this meta-analysis is that consuming probiotics may improve blood pressure, with a potentially greater effect when baseline blood pressure is elevated, multiple species of probiotics are consumed, and the duration of the intervention is ≥8 weeks (10)
Probiotics – Potentially Tackling Hypertension and its Associated Risk Factors
Cardio metabolic disorders such as hypertension involve many pathways and feedback loops for the maintenance of normal homeostatic balance. All the possible efforts to prevent hypertension and to halt the progression of hypertension so that other related comorbidities do not develop, and this approach needs prudent consideration. (2)
The legendary Heart Outcomes Prevention Evaluation (HOPE) study, which brought out that even modest reductions in systolic blood pressure (SBP) and diastolic blood pressure by 3.3 and 1.4 mmHg, respectively, were associated with a 22% reduction in the relative risk of cardiovascular mortality, myocardial infarction, or stroke. (11) In the light of such evidence, therapeutic modalities which are helpful to ensure the maintenance of normal homeostatic balance, have the potential to prevent as well as treat the disease with minimal or no side effects, have the highest nutritional value; and probiotics have exemplary body of evidence for such consideration.
Final Words
The burden of essential hypertension continues to remain huge, while its exact pathophysiology remains poorly defined. While medicine is taking strides in the direction of personalized care, hypertension management may be looked through as a cardio-metabolic disorder requiring a multi-pronged approach that may benefit high blood pressure and also, harmonize factors that breed and sustain high blood pressure and its long-term sequels. Emerging scientific findings have shed light on the important role of microbiota in high blood pressure and therapeutic potential with probiotics 1 in hypertension seems a step in the direction of holistic and individualized care.
The above article has been published by Medical Dialogues under the MD Brand Connect Initiative. For more details on probiotics, CLICK HERE
References
Adapted from:
1 Borse SP, Singh DP, Upadhyay D, Sharma V, Nivsarkar MA. Probiotic use in the management of hypertension: A new era of therapeutic management. Indian J Health Sci Biomed Res 2018;11:207-14
2 Sun J, Xu W, Wang G. The role of intestinal microflora and its possible mechanisms in hypertension. Lipid Cardiovasc Res 2016;2:8‑16
3 D'Argenio V, Salvatore F. The role of the gut microbiome in the healthy adult status. Clin Chim Acta 2015;451:97‑10
4 Mariat D, Firmesse O, Levenez F, Guimarăes V, Sokol H, Doré J, et al. The firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol 2009;9:123.
5 Pevsner‑Fischer M, Blacher E, Tatirovsky E, Ben‑Dov IZ, Elinav E. The gut microbiome and hypertension. Curr Opin Nephrol Hypertens 2017;26:1‑8
6 Emoto T, Yamashita T, Sasaki N, Hirota Y, Hayashi T, So A, et al. Analysis of gut microbiota in coronary artery disease patients: A possible link between gut microbiota and coronary artery disease. J Atheroscler Thromb 2016;23:908‑21.
7 Bengmark S. Colonic food: Pre‑ and probiotics. Am J Gastroenterol 2000;95:S5‑7.
8 Guandalini S. Probiotics for children with diarrhea: An update. J Clin Gastroenterol 2008;42 Suppl 2:S53‑7
9 Sobol C, Korotkov S, Belostotskaya G, Nesterov V. The influence of probiotics and probiotic product on respiration of mitochondria and intracellular calcium signal in cells of cardiovascular system. Biochem (Moscow) Suppl Ser A Membr Cell Biol 2013;7:294‑301
10 Khalesi S, Sun J, Buys N, Jayasinghe R. Effect of probiotics on blood pressure: A systematic review and meta‑analysis of randomized, controlled trials. Hypertension 2014;64:897‑903.
11 Sleight P, Yusuf S, Pogue J, Tsuyuki R, Diaz R, Probstfield J, et al. Blood‑pressure reduction and cardiovascular risk in HOPE study. Lancet 2001;358:2130‑1
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