Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Review Series - Recent Advances in the Management of Secondary Hypertension
  • Published:

Role of the microbiota in hypertension and antihypertensive drug metabolism

Hypertension Research volume 45, pages 246–253 (2022)Cite this article

Abstract

Recent evidence suggests that the gut microbiota plays an important role in the development and pathogenesis of hypertension. Dysbiosis, an imbalance in the composition and function of the gut microbiota, was shown to be associated with hypertension in both animal models and humans. In this review, we provide insights into host–microbiota interactions and summarize the evidence supporting the importance of the microbiota in blood pressure (BP) regulation. Metabolites produced by the gut microbiota, especially short-chain fatty acids (SCFAs), modulate BP and vascular responses. Harmful gut-derived metabolites, such as trimethylamine N-oxide and several uremic toxins, exert proatherosclerotic, prothrombotic, and proinflammatory effects. High-salt intake alters the composition of the microbiota, and this microbial alteration contributes to the pathogenesis of salt-sensitive hypertension. In addition, the microbiota may impact the metabolism of drugs and steroid hormones in the host. The drug-metabolizing activities of the microbiota affect the pharmacokinetic parameters of antihypertensive drugs and contribute to the pathogenesis of licorice-induced pseudohyperaldosteronism. Furthermore, the oral microbiota plays a role in BP regulation by producing nitric oxide, which lowers BP via its vasodilatory effects. Thus, antihypertensive intervention strategies targeting the microbiota, such as the use of prebiotics, probiotics, and postbiotics (e.g., SCFAs), are considered new therapeutic options for the treatment of hypertension.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Oyama JI, Node K. Gut microbiota and hypertension. Hypertens Res. 2019;42:741–3.

    Article  PubMed  Google Scholar 

  2. Onal EM, Afsar B, Covic A, Vaziri ND, Kanbay M. Gut microbiota and inflammation in chronic kidney disease and their roles in the development of cardiovascular disease. Hypertens Res. 2019;42:123–40.

    Article  PubMed  Google Scholar 

  3. Muralitharan RR, Jama HA, Xie L, Peh A, Snelson M, Marques FZ. Microbial peer pressure: the role of the gut microbiota in hypertension and its complications. Hypertension. 2020;76:1674–87.

    CAS  PubMed  Google Scholar 

  4. Avery EG, Bartolomaeus H, Maifeld A, Marko L, Wiig H, Wilck N, et al. The gut microbiome in hypertension: recent advances and future perspectives. Circ Res. 2021;128:934–50.

    Article  CAS  PubMed  Google Scholar 

  5. Choi MS, Yu JS, Yoo HH, Kim DH. The role of gut microbiota in the pharmacokinetics of antihypertensive drugs. Pharm Res. 2018;130:164–71.

    Article  CAS  Google Scholar 

  6. Morris DJ, Brem AS. Role of gut metabolism of adrenal corticosteroids and hypertension: clues gut-cleansing antibiotics give us. Physiol Genomics. 2019;51:83–89.

    Article  CAS  PubMed  Google Scholar 

  7. Yano Y. Blood pressure management in an ecosystem context. Hypertens Res. 2020;43:989–94.

    Article  PubMed  Google Scholar 

  8. Sun S, Lulla A, Sioda M, Winglee K, Wu MC, Jacobs DR Jr, et al. Gut microbiota composition and blood pressure. Hypertension. 2019;73:998–1006.

    Article  CAS  PubMed  Google Scholar 

  9. Palmu J, Lahti L, Niiranen T. Targeting gut microbiota to treat hypertension: a systematic review. Int J Environ Res Public Health. 2021;18:1248.

  10. Louca P, Nogal A, Wells PM, Asnicar F, Wolf J, Steves CJ, et al. Gut microbiome diversity and composition is associated with hypertension in women. J Hypertens. 2021;39:1810–1816.

  11. Smiljanec K, Lennon SL. Sodium, hypertension, and the gut: does the gut microbiota go salty? Am J Physiol Heart Circ Physiol. 2019;317:H1173–H1182.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Louca P, Menni C, Padmanabhan S. Genomic determinants of hypertension with a focus on metabolomics and the gut microbiome. Am J Hypertens. 2020;33:473–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 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.

    Article  CAS  PubMed  Google Scholar 

  14. Verhaar BJH, Collard D, Prodan A, Levels JHM, Zwinderman AH, Backhed F, et al. Associations between gut microbiota, faecal short-chain fatty acids, and blood pressure across ethnic groups: the HELIUS study. Eur Heart J. 2020;41:4259–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Palmu J, Salosensaari A, Havulinna AS, Cheng S, Inouye M, Jain M, et al. Association between the gut microbiota and blood pressure in a population cohort of 6953 individuals. J Am Heart Assoc. 2020;9:e016641.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Karbach SH, Schonfelder T, Brandao I, Wilms E, Hormann N, Jackel S, et al. Gut microbiota promote angiotensin II-induced arterial hypertension and vascular dysfunction. J Am Heart Assoc. 2016;5:e003698.

  17. Joe B, McCarthy CG, Edwards JM, Cheng X, Chakraborty S, Yang T, et al. Microbiota introduced to germ-free rats restores vascular contractility and blood pressure. Hypertension. 2020;76:1847–55.

    Article  CAS  PubMed  Google Scholar 

  18. Li J, Zhao F, Wang Y, Chen J, Tao J, Tian G, et al. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome. 2017;5:14.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Adnan S, Nelson JW, Ajami NJ, Venna VR, Petrosino JF, Bryan RM Jr, et al. Alterations in the gut microbiota can elicit hypertension in rats. Physiol Genomics. 2017;49:96–104.

    Article  CAS  PubMed  Google Scholar 

  20. Toral M, Robles-Vera I, de la Visitacion N, Romero M, Sanchez M, Gomez-Guzman M, et al. Role of the immune system in vascular function and blood pressure control induced by faecal microbiota transplantation in rats. Acta Physiol (Oxf). 2019;227:e13285.

    Article  CAS  Google Scholar 

  21. Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, et al. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci USA. 2009;106:3698–703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Mishima E, Fukuda S, Mukawa C, Yuri A, Kanemitsu Y, Matsumoto Y, et al. Evaluation of the impact of gut microbiota on uremic solute accumulation by a CE-TOFMS-based metabolomics approach. Kidney Int. 2017;92:634–45.

    Article  CAS  PubMed  Google Scholar 

  23. Kanemitsu Y, Mishima E, Maekawa M, Matsumoto Y, Saigusa D, Yamaguchi H, et al. Comprehensive and semi-quantitative analysis of carboxyl-containing metabolites related to gut microbiota on chronic kidney disease using 2-picolylamine isotopic labeling LC-MS/MS. Sci Rep. 2019;9:19075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Mishima E. Gut Microbiota and Systemic Uremic Solute Accumulation. Uremic Toxins and Organ Failure. Springer, Singapore. 2020. https://doi.org/10.1007/978-981-15-7793-2_3.

  25. Cheema MU, Pluznick JL. Gut microbiota plays a central role to modulate the plasma and fecal metabolomes in response to angiotensin II. Hypertension. 2019;74:184–93.

    Article  CAS  PubMed  Google Scholar 

  26. Marques FZ, Mackay CR, Kaye DM. Beyond gut feelings: how the gut microbiota regulates blood pressure. Nat Rev Cardiol. 2018;15:20–32.

    Article  PubMed  Google Scholar 

  27. Cummings JH, Pomare EW, Branch WJ, Naylor CP, Macfarlane GT. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut. 1987;28:1221–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Poll BG, Cheema MU, Pluznick JL. Gut microbial metabolites and blood pressure regulation: focus on SCFAs and TMAO. Physiol (Bethesda). 2020;35:275–84.

    CAS  Google Scholar 

  29. 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 USA. 2013;110:4410–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA. 2010;107:14691–6.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Bartolomaeus H, Balogh A, Yakoub M, Homann S, Marko L, Hoges S, et al. Short-chain fatty acid propionate protects from hypertensive cardiovascular damage. Circulation. 2019;139:1407–21.

    Article  CAS  PubMed  Google Scholar 

  32. Kim S, Goel R, Kumar A, Qi Y, Lobaton G, Hosaka K, et al. Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure. Clin Sci (Lond). 2018;132:701–18.

    Article  CAS  Google Scholar 

  33. Marques FZ, Nelson E, Chu PY, Horlock D, Fiedler A, Ziemann M, et al. High-fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice. Circulation. 2017;135:964–77.

    Article  CAS  PubMed  Google Scholar 

  34. Wu C, Chen Z, Zhang L, Zhu Y, Deng M, Huang C, et al. Sodium butyrate ameliorates deoxycorticosterone acetate/salt-induced hypertension and renal damage by inhibiting the MR/SGK1 pathway. Hypertens Res. 2021;44:168–78.

    Article  CAS  PubMed  Google Scholar 

  35. Aleixandre A, Miguel M. Dietary fiber and blood pressure control. Food Funct. 2016;7:1864–71.

    Article  CAS  PubMed  Google Scholar 

  36. Whelton SP, Hyre AD, Pedersen B, Yi Y, Whelton PK, He J. Effect of dietary fiber intake on blood pressure: a meta-analysis of randomized, controlled clinical trials. J Hypertens. 2005;23:475–81.

    Article  CAS  PubMed  Google Scholar 

  37. Kaye DM, Shihata WA, Jama HA, Tsyganov K, Ziemann M, Kiriazis H, et al. Deficiency of prebiotic fiber and insufficient signaling through gut metabolite-sensing receptors leads to cardiovascular disease. Circulation. 2020;141:1393–403.

    Article  CAS  PubMed  Google Scholar 

  38. 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.

    Article  CAS  PubMed  Google Scholar 

  39. Yang T, Magee KL, Colon-Perez LM, Larkin R, Liao YS, Balazic E, et al. Impaired butyrate absorption in the proximal colon, low serum butyrate and diminished central effects of butyrate on blood pressure in spontaneously hypertensive rats. Acta Physiol (Oxf). 2019;226:e13256.

    Article  CAS  Google Scholar 

  40. Yamashita T, Yoshida N, Emoto T, Saito Y, Hirata KI. Two gut microbiota-derived toxins are closely associated with cardiovascular diseases: a review. Toxins (Basel). 2021;13:297.

  41. Zhang WQ, Wang YJ, Zhang A, Ding YJ, Zhang XN, Jia QJ, et al. TMA/TMAO in hypertension: novel horizons and potential therapies. J Cardiovasc Transl Res. 2021. https://doi.org/10.1007/s12265-021-10115-x.

  42. Taguchi K, Fukami K, Elias BC, Brooks CR. Dysbiosis-related advanced glycation endproducts and trimethylamine n-oxide in chronic kidney disease. Toxins (Basel). 2021;13:361.

  43. Zhu W, Gregory JC, Org E, Buffa JA, Gupta N, Wang Z, et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell. 2016;165:111–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472:57–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19:576–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl J Med. 2013;368:1575–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ge X, Zheng L, Zhuang R, Yu P, Xu Z, Liu G, et al. The gut microbial metabolite trimethylamine N-oxide and hypertension risk: a systematic review and dose-response meta-analysis. Adv Nutr. 2020;11:66–76.

    PubMed  Google Scholar 

  48. Jiang S, Shui Y, Cui Y, Tang C, Wang X, Qiu X, et al. Gut microbiota dependent trimethylamine N-oxide aggravates angiotensin II-induced hypertension. Redox Biol. 2021;46:102115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ufnal M, Jazwiec R, Dadlez M, Drapala A, Sikora M, Skrzypecki J. Trimethylamine-N-oxide: a carnitine-derived metabolite that prolongs the hypertensive effect of angiotensin II in rats. Can J Cardiol. 2014;30:1700–5.

    Article  PubMed  Google Scholar 

  50. Lekawanvijit S, Kompa AR, Wang BH, Kelly DJ, Krum H. Cardiorenal syndrome: the emerging role of protein-bound uremic toxins. Circ Res. 2012;111:1470–83.

    Article  CAS  PubMed  Google Scholar 

  51. Mishima E, Fukuda S, Shima H, Hirayama A, Akiyama Y, Takeuchi Y, et al. Alteration of the intestinal environment by lubiprostone is associated with amelioration of adenine-induced CKD. J Am Soc Nephrol. 2015;26:1787–94.

    Article  CAS  PubMed  Google Scholar 

  52. Mishima E, Fukuda S, Kanemitsu Y, Saigusa D, Mukawa C, Asaji K, et al. Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model. Am J Physiol Ren Physiol. 2018;315:F824–F833.

    Article  CAS  Google Scholar 

  53. Vanholder R, Schepers E, Pletinck A, Nagler EV, Glorieux G. The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: a systematic review. J Am Soc Nephrol. 2014;25:1897–907.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Yamaguchi K, Yisireyili M, Goto S, Kato K, Cheng XW, Nakayama T, et al. Indoxyl sulfate-induced vascular calcification is mediated through altered notch signaling pathway in vascular smooth muscle cells. Int J Med Sci. 2020;17:2703–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Chao CT, Lin SH. Uremic vascular calcification: the pathogenic roles and gastrointestinal decontamination of uremic toxins. Toxins (Basel). 2020;12:812.

  56. Toda T, Saito N, Ikarashi N, Ito K, Yamamoto M, Ishige A, et al. Intestinal flora induces the expression of Cyp3a in the mouse liver. Xenobiotica. 2009;39:323–34.

    Article  CAS  PubMed  Google Scholar 

  57. Mishima E, Ichijo M, Kawabe T, Kikuchi K, Akiyama Y, Toyohara T, et al. Germ-free conditions modulate host purine metabolism, exacerbating adenine-induced kidney damage. Toxins (Basel). 2020;12:547.

  58. Noh K, Kang YR, Nepal MR, Shakya R, Kang MJ, Kang W, et al. Impact of gut microbiota on drug metabolism: an update for safe and effective use of drugs. Arch Pharm Res. 2017;40:1345–55.

    Article  CAS  PubMed  Google Scholar 

  59. Yoo HH, Kim IS, Yoo DH, Kim DH. Effects of orally administered antibiotics on the bioavailability of amlodipine: gut microbiota-mediated drug interaction. J Hypertens. 2016;34:156–62.

    Article  CAS  PubMed  Google Scholar 

  60. Kato R, Yuasa H, Inoue K, Iwao T, Tanaka K, Ooi K, et al. Effect of Lactobacillus casei on the absorption of nifedipine from rat small intestine. Drug Metab Pharmacokinet. 2007;22:96–102.

    Article  CAS  PubMed  Google Scholar 

  61. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Maier L, Pruteanu M, Kuhn M, Zeller G, Telzerow A, Anderson EE, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018;555:623–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Robles-Vera I, Toral M, de la Visitacion N, Sanchez M, Gomez-Guzman M, Munoz R, et al. Changes to the gut microbiota induced by losartan contributes to its antihypertensive effects. Br J Pharm. 2020;177:2006–23.

    Article  CAS  Google Scholar 

  64. Wu D, Tang X, Ding L, Cui J, Wang P, Du X, et al. Candesartan attenuates hypertension-associated pathophysiological alterations in the gut. Biomed Pharmacother. 2019;116:109040.

    Article  CAS  PubMed  Google Scholar 

  65. Honour J. The possible involvement of intestinal bacteria in steroidal hypertension. Endocrinology. 1982;110:285–7.

    Article  CAS  PubMed  Google Scholar 

  66. Honour JW. Historical perspective: gut dysbiosis and hypertension. Physiol Genomics. 2015;47:443–6.

    Article  CAS  PubMed  Google Scholar 

  67. Yao Z, Zhao M, Gong Y, Chen W, Wang Q, Fu Y, et al. Relation of gut microbes and L-thyroxine through altered thyroxine metabolism in subclinical hypothyroidism subjects. Front Cell Infect Microbiol. 2020;10:495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Farese RV Jr., Biglieri EG, Shackleton CH, Irony I, Gomez-Fontes R. Licorice-induced hypermineralocorticoidism. N Engl J Med. 1991;325:1223–7.

    Article  PubMed  Google Scholar 

  69. Sasaki K, Yonebayashi S, Yoshida M, Shimizu K, Aotsuka T, Takayama K. Improvement in the bioavailability of poorly absorbed glycyrrhizin via various non-vascular administration routes in rats. Int J Pharm. 2003;265:95–102.

    Article  CAS  PubMed  Google Scholar 

  70. Zhu Y, Liu Y, Wu C, Li H, Du H, Yu H, et al. Enterococcus faecalis contributes to hypertension and renal injury in Sprague-Dawley rats by disturbing lipid metabolism. J Hypertens. 2021;39:1112–24.

    Article  CAS  PubMed  Google Scholar 

  71. Ishiuchi K, Morinaga O, Ohkita T, Tian C, Hirasawa A, Mitamura M, et al. 18beta-glycyrrhetyl-3-O-sulfate would be a causative agent of licorice-induced pseudoaldosteronism. Sci Rep. 2019;9:1587.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Kurtz TW, DiCarlo SE, Pravenec M, Morris RC. Changing views on the common physiologic abnormality that mediates salt sensitivity and initiation of salt-induced hypertension: Japanese research underpinning the vasodysfunction theory of salt sensitivity. Hypertens Res. 2019;42:6–18.

    Article  CAS  PubMed  Google Scholar 

  73. Wilck N, Matus MG, Kearney SM, Olesen SW, Forslund K, Bartolomaeus H, et al. Salt-responsive gut commensal modulates TH17 axis and disease. Nature. 2017;551:585–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Norlander AE, Saleh MA, Kamat NV, Ko B, Gnecco J, Zhu L, et al. Interleukin-17A regulates renal sodium transporters and renal injury in angiotensin II-induced hypertension. Hypertension. 2016;68:167–74.

    Article  CAS  PubMed  Google Scholar 

  75. Yan X, Jin J, Su X, Yin X, Gao J, Wang X, et al. Intestinal flora modulates blood pressure by regulating the synthesis of intestinal-derived corticosterone in high salt-induced hypertension. Circ Res. 2020;126:839–53.

    Article  CAS  PubMed  Google Scholar 

  76. Nakamura T, Kurihara I, Kobayashi S, Yokota K, Murai-Takeda A, Mitsuishi Y, et al. Intestinal mineralocorticoid receptor contributes to epithelial sodium channel-mediated intestinal sodium absorption and blood pressure regulation. J Am Heart Assoc. 2018;7:e008259.

  77. Chen L, He FJ, Dong Y, Huang Y, Wang C, Harshfield GA, et al. Modest sodium reduction increases circulating short-chain fatty acids in untreated hypertensives: a randomized, double-blind, placebo-controlled trial. Hypertension. 2020;76:73–79.

    Article  CAS  PubMed  Google Scholar 

  78. Kapil V, Khambata RS, Robertson A, Caulfield MJ, Ahluwalia A. Dietary nitrate provides sustained blood pressure lowering in hypertensive patients: a randomized, phase 2, double-blind, placebo-controlled study. Hypertension. 2015;65:320–7.

    Article  CAS  PubMed  Google Scholar 

  79. Barbadoro P, Ponzio E, Coccia E, Prospero E, Santarelli A, Rappelli GGL, et al. Association between hypertension, oral microbiome and salivary nitric oxide: a case-control study. Nitric Oxide. 2021;106:66–71.

    Article  CAS  PubMed  Google Scholar 

  80. Kapil V, Haydar SM, Pearl V, Lundberg JO, Weitzberg E, Ahluwalia A. Physiological role for nitrate-reducing oral bacteria in blood pressure control. Free Radic Biol Med. 2013;55:93–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ko CY, Hu AK, Chou D, Huang LM, Su HZ, Yan FR, et al. Analysis of oral microbiota in patients with obstructive sleep apnea-associated hypertension. Hypertens Res. 2019;42:1692–1700.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Pignatelli P, Fabietti G, Ricci A, Piattelli A, Curia MC. How periodontal disease and presence of nitric oxide reducing oral bacteria can affect blood pressure. Int J Mol Sci. 2020;21:7538.

  83. Czesnikiewicz-Guzik M, Osmenda G, Siedlinski M, Nosalski R, Pelka P, Nowakowski D, et al. Causal association between periodontitis and hypertension: evidence from Mendelian randomization and a randomized controlled trial of non-surgical periodontal therapy. Eur Heart J. 2019;40:3459–70.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. 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.

    Article  CAS  PubMed  Google Scholar 

  85. Chi C, Li C, Wu D, Buys N, Wang W, Fan H, et al. Effects of probiotics on patients with hypertension: a systematic review and meta-analysis. Curr Hypertens Rep. 2020;22:34.

    Article  PubMed  Google Scholar 

  86. Maifeld A, Bartolomaeus H, Lober U, Avery EG, Steckhan N, Marko L, et al. Fasting alters the gut microbiome reducing blood pressure and body weight in metabolic syndrome patients. Nat Commun. 2021;12:1970.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Ahmed S, Spence JD. Sex differences in the intestinal microbiome: interactions with risk factors for atherosclerosis and cardiovascular disease. Biol Sex Differ. 2021;12:35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Muralitharan RR, Nakai ME, Marques FZ. The conundrum of the gut microbiome and blood pressure: the importance of studying sex and ethnicity. Eur Heart J. 2020;41:4268–70.

    Article  PubMed  Google Scholar 

  89. Marques FZ, Jama HA, Tsyganov K, Gill PA, Rhys-Jones D, Muralitharan RR, et al. Guidelines for transparency on gut microbiome studies in essential and experimental hypertension. Hypertension. 2019;74:1279–93.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Figures were created using BioRender (https://biorender.com/). This work was supported in part by Grants-in-Aid for Scientific Research (18K08198 and 20KK0363 to E.M.) from the Japan Society for the Promotion of Science (JSPS) and a grant from the Japan Foundation for Applied Enzymology (to E.M.).

Author information

Authors and Affiliations

  1. Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

    Eikan Mishima & Takaaki Abe

  2. Institute of Metabolism and Cell Death, Helmholtz Zentrum München, Neuherberg, Germany

    Eikan Mishima

  3. Department of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan

    Takaaki Abe

  4. Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine, Sendai, Japan

    Takaaki Abe

Authors
  1. Eikan Mishima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takaaki Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eikan Mishima.

Ethics declarations

Conflict of interest

The authors declare no competing interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mishima, E., Abe, T. Role of the microbiota in hypertension and antihypertensive drug metabolism. Hypertens Res 45, 246–253 (2022). https://doi.org/10.1038/s41440-021-00804-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-021-00804-0

Keywords

This article is cited by

Search

Advanced search

Quick links