Antihypertensive Effects of Probiotics

  • Iñaki Robles-Vera
  • Marta Toral
  • Miguel Romero
  • Rosario Jiménez
  • Manuel Sánchez
  • Francisco Pérez-Vizcaíno
  • Juan DuarteEmail author
Gut Microbiome, Sympathetic Nervous System, and Hypertension (MK Raizada and EM Richards, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Gut Microbiome, Sympathetic Nervous System, and Hypertension


Purpose of Review

The present review focuses in the hypertension-associated changes in the microbiota and the current insights regarding the impact of probiotics on blood pressure in animal models and in human hypertensive patients.

Recent Findings

Gut dysbiosis in hypertension is characterized by (i) the gut microbioma that is less diverse and less rich with an increased Firmicutes/Bacteroidetes ratio and (ii) a decrease in acetate- and butyrate-producing bacteria and an increase in lactate-producing bacterial populations. The meta-analysis of the human studies supports that supplementation with probiotics reduces blood pressure. The mechanism of this antihypertensive effect of probiotics and its protective effect on endothelial function has not been fully elucidated.


Further investigations are needed to clarify if the effects of probiotic bacteria result from the changes in the gut microbiota and its metabolic by-products; the restoration of the gut barrier function; and the effects on endotoxemia, inflammation, and renal sympathetic nerve activity.


Probiotic bacteria Gut microbiota Hypertension Endothelial dysfunction 



This work was supported by Grants from Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad (SAF2014-55523-R); Junta de Andalucía (Proyecto de excelencia P12-CTS-2722 and CTS 164) with funds from the European Union; and by the Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (RIC, RD12/0042/0011, CIBER-Enfermedades Cardiovasculares), Spain. M.S. is a postdoctoral fellow of Junta de Andalucía, and M.R. is a postdoctoral fellow of University of Granada.

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Wong ND, Glovaci D, Wong K, Malik S, Franklin SS, Wygant G, Iloeje U. Global cardiovascular disease risk assessment in United States adults with diabetes. Diab Vasc Dis Res. 2012;9:146–52.CrossRefPubMedGoogle Scholar
  2. 2.
    Turnbull F. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet. 2003;362:1527–35.CrossRefPubMedGoogle Scholar
  3. 3.
    Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, et al. 2013 ESH/ESC practice guidelines for the management of arterial hypertension. Blood Press. 2014;23:3–16.CrossRefPubMedGoogle Scholar
  4. 4.
    Tamargo J, Duarte J, Ruilope LM. New antihypertensive drugs under development. Curr Med Chem. 2015;22:305–42.CrossRefPubMedGoogle Scholar
  5. 5.
    • Yang T, Santisteban MM, Rodriguez V, Li E, Ahmari N, Carvajal JM, et al. Gut dysbiosis is linked to hypertension. Hypertension. 2015;65:1331–40. This article described for the first time the characteristic of gut dysbiosis in animal and human with hypertension. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    • Santisteban MM, Qi Y, Zubcevic J, Kim S, Yang T, Shenoy V, et al. Hypertension-linked pathophysiological alterations in the gut. Circ Res. 2016a; doi: 10.1161/CIRCRESAHA.116.309006. This article shows a hypothesis linking gut microbiota dysbiosis and high blood pressure. A dysfunctional sympathetic-gut communication is associated with gut pathology, dysbiosis, and inflammation, and plays a key role in hypertension. PubMedCentralGoogle Scholar
  7. 7.
    Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59–65.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    • Karbach SH, Schönfelder T, Brandão I, Wilms E, Hörmann N, Jäckel S, et al. Gut microbiota promote angiotensin II-induced arterial hypertension and vascular dysfunction. J Am Heart Assoc. 2016;5:e003698. This article described that gut microbiota facilitate angiotensin II-induced vascular dysfunction and hypertension involving vascular Th17 immune cell infiltration and inflammation. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    • Pluznick JL, Protzko RJ, Gevorgyan H, Peterlin Z, Sipos A, Han J, et al. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci U S A. 2013;110:4410–5. This article described how gut microbiota, through metabolic byproducts such as short chain fatty acids, regulated blood pressure involving olfactory receptors. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Qi Y, Aranda JM, Rodriguez V, Raizada MK, Pepine CJ. Impact of antibiotics on arterial blood pressure in a patient with resistant hypertension—a case report. Int J Cardiol. 2015;201:157–8.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Durgan DJ, Ganesh BP, Cope JL, Ajami NJ, Phillips SC, Petrosino JF, et al. Role of the gut microbiome in obstructive sleep apnea-induced hypertension. Hypertension. 2016;67:469–74.PubMedGoogle Scholar
  12. 12.
    Xu P, Li M, Zhang J, Zhang T. Correlation of intestinal microbiota with overweight and obesity in Kazakh school children. BMC Microbiol. 2012;12:283.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Gomez-Arango LF, Barrett HL, McIntyre HD, Callaway LK, Morrison M, Dekker Nitert M, et al. Increased systolic and diastolic blood pressure is associated with altered gut microbiota composition and butyrate production in early pregnancy. Hypertension. 2016;68:974–81.CrossRefPubMedGoogle Scholar
  14. 14.
    • Gómez-Guzmán M, Toral M, Romero M, Jiménez R, Galindo P, Sánchez M, et al. Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats. Mol Nutr Food Res. 2015;59:2326–36. This article described for the first time the blood pressure lowering properties of probiotics in genetic hypertension. CrossRefPubMedGoogle Scholar
  15. 15.
    Grangette C. Bifidobacteria and subsets of dendritic cells: friendly players in immune regulation! Gut. 2012;61:331–2.CrossRefPubMedGoogle Scholar
  16. 16.
    Bomfim GF, Dos Santos RA, Oliveira MA, Giachini FR, Akamine EH, Tostes RC, et al. Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats. Clin Sci (Lond). 2012;122:535–43.CrossRefGoogle Scholar
  17. 17.
    Xu J, Ahrén IL, Prykhodko O, Olsson C, Ahrné S, Molin G. Intake of blueberry fermented by Lactobacillus plantarum affects the gut microbiota of L-NAME treated rats. Evid Based Complement Alternat Med. 2013;2013:809128.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Petriz BA, Castro AP, Almeida JA, Gomes CP, Fernandes GR, Kruger RH, et al. Exercise induction of gut microbiota modifications in obese, non-obese and hypertensive rats. BMC Genomics. 2014;15:511.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Lyte M. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. BioEssays. 2011;33:574–81.CrossRefPubMedGoogle Scholar
  20. 20.
    Bennett BJ, de Aguiar Vallim TQ, Wang Z, Shih DM, Meng Y, Gregory J, et al. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab. 2013;17:49–60.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Cani PD, Osto M, Geurts L, Everard A. Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes. 2012;3:279–88.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    • Toral M, Gómez-Guzmán M, Jiménez R, Romero M, Sánchez M, Utrilla MP, et al. The probiotic Lactobacillus coryniformis CECT5711 reduces the vascular pro-oxidant and pro-inflammatory status in obese mice. Clin Sci (Lond). 2014;127:33–45. This article established a link among endotoxaemia, endothelial dysfunction and hypertension, and their regulation by probiotics. CrossRefGoogle Scholar
  23. 23.
    Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci U S A. 2008;105:16767–72.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461:1282–6.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Lathrop SK, Bloom SM, Rao SM, Nutsch K, Lio CW, Santacruz N, et al. Peripheral education of the immune system by colonic commensal microbiota. Nature. 2011;478:250–4.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Iraporda C, Errea A, Romanin DE, Cayet D, Pereyra E, Pignataro O, et al. Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells. Immunobiology. 2015;220:1161–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Chang PV, Hao L, Offermanns S, Medzhitov R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci U S A. 2014;111:2247–52.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Park J, Kim M, Kang SG, Jannasch AH, Cooper B, Patterson J, et al. Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway. Mucosal Immunol. 2015;8:80–93.CrossRefPubMedGoogle Scholar
  29. 29.
    Madhur MS, Lob HE, McCann LA, Iwakura Y, Blinder Y, Guzik TJ, et al. Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction. Hypertension. 2010;55:500–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Martin FP, Wang Y, Sprenger N, Yap IK, Lundstedt T, Lek P, et al. Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model. Mol Syst Biol. 2008;4:157.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Kim S, Wang G, Lobaton G, Li E, Yang T, Raizada M. OS 05–10 The microbial metabolite, butyrate attenuates angiotensin II-induced hypertension and dysbiosis. J Hypertens. 2016;34-ISH 2016 Abstract Book:e60-e61.Google Scholar
  32. 32.
    Marques FZ, Nelson EM, Chu PY, Horlock D, Fiedler A, Ziemann M, et al. High fibre diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in DOCA-salt hypertensive mice. Circulation. 2016; doi: 10.1161/CIRCULATIONAHA.116.024545.Google Scholar
  33. 33.
    Miyamoto J, Kasubuchi M, Nakajima A, Irie J, Itoh H, Kimura I. The role of short-chain fatty acid on blood pressure regulation. Curr Opin Nephrol Hypertens. 2016;25:379–83.CrossRefPubMedGoogle Scholar
  34. 34.
    Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761–72.CrossRefPubMedGoogle Scholar
  35. 35.
    Dinh QN, Drummond GR, Sobey CG, Chrissobolis S. Roles of inflammation, oxidative stress, and vascular dysfunction in hypertension. Biomed Res Int. 2014;2014:406960.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Eissler R, Schmaderer C, Rusai K, Kühne L, Sollinger D, Lahmer T, et al. Hypertension augments cardiac toll-like receptor 4 expression and activity. Hypertens Res. 2011;34:551–8.CrossRefPubMedGoogle Scholar
  37. 37.
    Sollinger D, Eißler R, Lorenz S, Strand S, Chmielewski S, Aoqui C, et al. Damage-associated molecular pattern activated toll-like receptor 4 signalling modulates blood pressure in L-NAME-induced hypertension. Cardiovasc Res. 2014;101:464–72.CrossRefPubMedGoogle Scholar
  38. 38.
    Liang CF, Liu JT, Wang Y, Xu A, Vanhoutte PM. Toll-like receptor 4 mutation protects obese mice against endothelial dysfunction by decreasing NADPH oxidase isoforms 1 and 4. Arterioscler Thromb Vasc Biol. 2013;33:777–84.CrossRefPubMedGoogle Scholar
  39. 39.
    Santisteban MM, Kim S, Pepine CJ, Raizada MK. Brain-gut-bone marrow axis: implications for hypertension and related therapeutics. Circ Res. 2016b;118:1327–36. ReviewCrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11:506–14.CrossRefPubMedGoogle Scholar
  41. 41.
    Cani PD, Delzenne NM. The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des. 2009;15:1546–58.CrossRefPubMedGoogle Scholar
  42. 42.
    Singh VP, Sharma J, Babu S, Rizwanulla SA. Role of probiotics in health and disease: a review. J Pak Med Assoc. 2013;63:253–7.PubMedGoogle Scholar
  43. 43.
    Rerksuppaphol S, Rerksuppaphol L. A randomized double-blind controlled trial of Lactobacillus acidophilus plus Bifidobacterium bifidum versus placebo in patients with hypercholesterolemia. J Clin Diagn Res. 2015;9:KC01–4.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Ishimwe N, Daliri EB, Lee BH, Fang F, Du G. The perspective on cholesterol-lowering mechanisms of probiotics. Mol Nutr Food Res. 2015;59:94–105.CrossRefPubMedGoogle Scholar
  45. 45.
    Chan YK, Brar MS, Kirjavainen PV, Chen Y, Peng J, Li D, et al. High fat diet induced atherosclerosis is accompanied with low colonic bacterial diversity and altered abundances that correlates with plaque size, plasma A-FABP and cholesterol: a pilot study of high fat diet and its intervention with Lactobacillus rhamnosus GG (LGG) or telmisartan in ApoE(−/−) mice. BMC Microbiol. 2016a;16:264.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Chan YK, El-Nezami H, Chen Y, Kinnunen K, Kirjavainen PV. Probiotic mixture VSL#3 reduce high fat diet induced vascular inflammation and atherosclerosis in ApoE(−/−) mice. AMB Express. 2016b;6:61.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Gan XT, Ettinger G, Huang CX, Burton JP, Haist JV, Rajapurohitam V, et al. Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat. Circ Heart Fail. 2014;7:491–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Thushara RM, Gangadaran S, Solati Z, Moghadasian MH. Cardiovascular benefits of probiotics: a review of experimental and clinical studies. Food Funct. 2016;7:632–42.CrossRefPubMedGoogle Scholar
  49. 49.
    Upadrasta A, Madempudi RS. Probiotics and blood pressure: current insights. Integr Blood Press Control. 2016;9:33–42.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Daliri EB, Lee BH, Oh DH. Current perspectives on antihypertensive probiotics. Probiotics Antimicrob Proteins. 2016; doi: 10.1007/s12602-016-9241-y.PubMedGoogle Scholar
  51. 51.
    de Brito Alves JL, de Sousa VP, Cavalcanti Neto MP, Magnani M, Braga VA, da Costa-Silva JH, et al. New insights on the use of dietary polyphenols or probiotics for the management of arterial hypertension. Front Physiol. 2016;7:448.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Tanida M, Yamano T, Maeda K, Okumura N, Fukushima Y, Nagai K. Effects of intraduodenal injection of Lactobacillus johnsonii La1 on renal sympathetic nerve activity and blood pressure in urethane-anesthetized rats. Neurosci Lett. 2005;389:109–14.CrossRefPubMedGoogle Scholar
  53. 53.
    Tanida M, Imanishi K, Akashi H, Kurata Y, Chonan O, Naito E, et al. Injection of Lactobacillus casei strain Shirota affects autonomic nerve activities in a tissue-specific manner, and regulates glucose and lipid metabolism in rats. J Diabetes Investig. 2014;5:153–61.CrossRefPubMedGoogle Scholar
  54. 54.
    Matsuzaki T, Takagi A, Ikemura H, Matsuguchi T, Yokokura T. Intestinal microflora: probiotics and autoimmunity. J Nutr. 2007;137:798S–802S.PubMedGoogle Scholar
  55. 55.
    Arribas B, Rodríguez-Cabezas ME, Comalada M, Bailón E, Camuesco D, Olivares M, et al. Evaluation of the preventative effects exerted by Lactobacillus fermentum in an experimental model of septic shock induced in mice. Br J Nutr. 2009;101:51–8.CrossRefPubMedGoogle Scholar
  56. 56.
    Arribas B, Garrido-Mesa N, Perán L, Camuesco D, Comalada M, Bailón E, et al. The immunomodulatory properties of viable Lactobacillus salivarius ssp. salivarius CECT5713 are not restricted to the large intestine. Eur J Nutr. 2012;51:365–74.CrossRefPubMedGoogle Scholar
  57. 57.
    Yap WB, Ahmad FM, Lim YC, Zainalabidin S. Lactobacillus casei strain C1 attenuates vascular changes in spontaneously hypertensive rats. Korean J Physiol Pharmacol. 2016;20:621–8.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Friques AG, Arpini CM, Kalil IC, Gava AL, Leal MA, Porto ML, et al. Chronic administration of the probiotic kefir improves the endothelial function in spontaneously hypertensive rats. J Transl Med. 2015;13:390.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Blanton C, He Z, Gottschall-Pass KT, Sweeney MI. Probiotics blunt the anti-hypertensive effect of blueberry feeding in hypertensive rats without altering hippuric acid production. PLoS One. 2015;10:e0142036.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    • 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. A meta-analysis of nine trials showed that consuming probiotics decreased blood pressure. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Iñaki Robles-Vera
    • 1
  • Marta Toral
    • 1
  • Miguel Romero
    • 1
    • 2
  • Rosario Jiménez
    • 1
    • 2
  • Manuel Sánchez
    • 1
  • Francisco Pérez-Vizcaíno
    • 3
  • Juan Duarte
    • 1
    • 2
    Email author
  1. 1.Department of Pharmacology, School of PharmacyUniversity of Granada, CIBER-Enfermedades Cardiovasculares (CiberCV)GranadaSpain
  2. 2.Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA)GranadaSpain
  3. 3.Department of Pharmacology, School of MedicineComplutense University of Madrid; CIBER Enfermedades Respiratorias (Ciberes) and Instituto de Investigación Sanitaria Gregorio Marañón (IISGM)MadridSpain

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