Gut microbiota and arterial hypertension (a literature review)
DOI:
https://doi.org/10.14739/2310-1210.2020.4.208409Keywords:
gut microbiota, hypertension, Firmicutes/Bacteroidetes, endotoxinemia, trimethylamine N-oxide, short chain fatty acids, butyrateAbstract
The aim of the work was to analyze and collate literature data on the role of the gut microbiota disorders in the pathogenesis of arterial hypertension and to determine the prospects for further research.
Results. The article presents the results of studies that indicate the significant role of various components of the gut microbiota disorders in the development of arterial hypertension in experimental animals and humans. The accumulated data allow for consideration of the gut microiota as a part of a complex system involved in the regulation of blood pressure. Studies using fecal microbiota transplantation showed that the fecal microbiome transfer from hypertensive animals or patients with arterial hypertension to normotensive animals led to an increase in blood pressure in the latter. At the same time, transplantation of microbiota from normotensive animals to hypertensive resulted in a decrease in blood pressure in recipients. It was revealed that the leading dysbiotic factors that play the most significant role in the mechanisms of arterial hypertension development are the composition of the gut microbiota, the Firmicutes/Bacteroidetes ratio, the state of the tight junction proteins in the gut epithelium, the gut epithelial permeability to lipopolysaccharides, endotoxinemia, subclinical systemic inflammation, the levels of trimethylamine N-oxide and short-chain fatty acids production, as well as the relationship between the latter and specific Olfr and GPR receptors.
Conclusions. The analyzed results of the studies indicate the involvement of gut microbiota disorders in the pathogenesis of arterial hypertension. However, the role of individual components of the gut microbiota in the mechanisms of blood pressure regulation and the development of hypertensive damage to target organs and complications remains poorly understood. Promising areas of the research are the development of informative methods for assessing the state of gut microbiota and fundamentally new approaches for reducing the risk of hypertension development and progression by the correction of occurring disorders.
References
- Williams, B., Mancia, G., Spiering, W., Agabiti Rosei, E., Azizi, M., Burnier, M., Clement, D. L., Coca, A., de Simone, G., Dominiczak, A., Kahan, T., Mahfoud, F., Redon, J., Ruilope, L., Zanchetti, A., Kerins, M., Kjeldsen, S. E., Kreutz, R., Laurent, S., Lip, G., … ESC Scientific Document Group. (2018). 2018 ESC/ESH Guidelines for the management of arterial hypertension. European heart journal, 39(33), 3021-3104. https://doi.org/10.1093/eurheartj/ehy339
- Camm, A., Lüscher, T., Maurer, G., & Serruys, P. (Eds.). (2019). The ESC textbook of cardiovascular medicine (3rd ed.). Oxford University Press/European Society of Cardiology. https://doi.org/10.1093/med/9780199566990.001.0001
- Kovalenko, V. M., Lutai, M. I., Sirenko, Yu. M., & Sychov, O. S. (Eds.). (2018). Sertsevo-sudynni zakhvoriuvannia. Klasyfikatsiia, standarty diahnostyky ta likuvannia [Cardiovascular diseases. Classification, standards of diagnostic and therapeutic standards] (3rd ed.). Morion. [in Ukrainian].
- Koval, S., Iushko, K., & Starchenko, T. (2018). Relations of Apelin with Cardiac Remodeling in Patients with Hypertension and Type 2 Diabetes. Folia Medica, 60(1), 117-123. https://doi.org/10.1515/folmed-2017-0066
- Koval, S. M., Yushko, K. O., Snihurska, I. O., Starchenko, T. G., Pankiv, V. I., Lytvynova, O. M., & Mysnychenko, O. V. (2019). Relations of angiotensin-(1-7) with hemodynamic and cardiac structural and functional parameters in patients with hypertension and type 2 diabetes. Arterial Hypertension, 23(3), 183-189. https://doi.org/10.5603/ah.a2019.0012
- Koval, S., Snihurska, I., Yushko, K., Lytvynova, O., & Berezin, A. (2019). Plasma microRNA-133а level in patients with essential arterial hypertension. Georgian medical news, (290), 52-59.
- Mancia, G., Grassi, G., Tsioufis, K. P., Dominiczak, A. F., & Rosei, E. A. (Eds.). (2019). Manual of Hypertension of the European Society of Hypertension (3rd ed.). CRC Press. https://doi.org/10.1201/9780429199189
- Xu, H., Wang, X., Feng, W., Liu, Q., Zhou, S., Liu, Q., & Cai, L. (2020). The gut microbiota and its interactions with cardiovascular disease. Microbial biotechnology, 13(3), 637-656. https://doi.org/10.1111/1751-7915.13524
- Kazemian, N., Mahmoudi, M., Halperin, F., Wu, J. C., & Pakpour, S. (2020). Gut microbiota and cardiovascular disease: opportunities and challenges. Microbiome, 8(1), Article 36. https://doi.org/10.1186/s40168-020-00821-0
- Tang, W. H., Kitai, T., & Hazen, S. L. (2017). Gut Microbiota in Cardiovascular Health and Disease. Circulation research, 120(7), 1183-1196. https://doi.org/10.1161/CIRCRESAHA.117.309715
- Richards, E. M., Pepine, C. J., Raizada, M. K., & Kim, S. (2017). The Gut, Its Microbiome, and Hypertension. Current Hypertension Reports, 19(4), Article 36. https://doi.org/10.1007/s11906-017-0734-1
- Katsimichas, T., Antonopoulos, A. S., Katsimichas, A., Ohtani, T., Sakata, Y., & Tousoulis, D. (2019). The intestinal microbiota and cardiovascular disease. Cardiovascular Research, 115(10), 1471-1486. https://doi.org/10.1093/cvr/cvz135
- Nikonov, E. L., & E. N., Popova. (Eds.). (2019). Mikrobiota [Microbiota]. Media Sfera. [in Russian].
- Busnelli, M., Manzini, S., & Chiesa, G. (2019). The Gut Microbiota Affects Host Pathophysiology as an Endocrine Organ: A Focus on Cardiovascular Disease. Nutrients, 12(1), Article 79. https://doi.org/10.3390/nu12010079
- Sánchez, B., Delgado, S., Blanco-Míguez, A., Lourenço, A., Gueimonde, M., & Margolles, A. (2017). Probiotics, gut microbiota, and their influence on host health and disease. Molecular Nutrition & Food Research, 61(1), Article 1600240. https://doi.org/10.1002/mnfr.201600240
- Miro-Blanch, J., & Yanes, O. (2019). Epigenetic Regulation at the Interplay Between Gut Microbiota and Host Metabolism. Frontiers in Genetics, 10, Article 638. https://doi.org/10.3389/fgene.2019.00638
- Mithieux, G. (2018). Gut Microbiota and Host Metabolism: What Relationship. Neuroendocrinology, 106(4), 352-356. https://doi.org/10.1159/000484526
- Costea, P. I., Hildebrand, F., Arumugam, M., Bäckhed, F., Blaser, M. J., Bushman, F. D., de Vos, W. M., Ehrlich, S. D., Fraser, C. M., Hattori, M., Huttenhower, C., Jeffery, I. B., Knights, D., Lewis, J. D., Ley, R. E., Ochman, H., O'Toole, P. W., Quince, C., Relman, D. A., Shanahan, F., … Bork, P. (2018). Enterotypes in the landscape of gut microbial community composition. Nature Microbiology, 3(1), 8-16. https://doi.org/10.1038/s41564-017-0072-8
- Koliada, A., Syzenko, G., Moseiko, V., Budovska, L., Puchkov, K., Perederiy, V., Gavalko, Y., Dorofeyev, A., Romanenko, M., Tkach, S., Sineok, L., Lushchak, O., & Vaiserman, A. (2017). Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population. BMC Microbiology, 17(1), Article 120. https://doi.org/10.1186/s12866-017-1027-1
- Mushtaq, N., Hussain, S., Zhang, S., Yuan, L., Li, H., Ullah, S., Wang, Y., & Xu, J. (2019). Molecular characterization of alterations in the intestinal microbiota of patients with grade 3 hypertension. International Journal of Molecular Medicine, 44(2), 513-522. https://doi.org/10.3892/ijmm.2019.4235
- Oyama, J. I., & Node, K. (2019). Gut microbiota and hypertension. Hypertension Research, 42(5), 741-743. https://doi.org/10.1038/s41440-018-0203-5
- Kang, Y., & Cai, Y. (2018). Gut microbiota and hypertension: From pathogenesis to new therapeutic strategies. Clinics and Research in Hepatology and Gastroenterology, 42(2), 110-117. https://doi.org/10.1016/j.clinre.2017.09.006
- Pevsner-Fischer, M., Blacher, E., Tatirovsky, E., Ben-Dov, I. Z., & Elinav, E. (2017). The gut microbiome and hypertension. Current Opinion in Nephrology and Hypertension, 26(1), 1-8. https://doi.org/10.1097/MNH.0000000000000293
- Hsu, C. N., Hou, C. Y., Lee, C. T., Chan, J., & Tain, Y. L. (2019). The Interplay between Maternal and Post-Weaning High-Fat Diet and Gut Microbiota in the Developmental Programming of Hypertension. Nutrients, 11(9), Article 1982. https://doi.org/10.3390/nu11091982
- Sun, S., Lulla, A., Sioda, M., Winglee, K., Wu, M. C., Jacobs, D. R., Jr, Shikany, J. M., Lloyd-Jones, D. M., Launer, L. J., Fodor, A. A., & Meyer, K. A. (2019). Gut Microbiota Composition and Blood Pressure. Hypertension, 73(5), 998-1006. https://doi.org/10.1161/HYPERTENSIONAHA.118.12109
- Li, J., Zhao, F., Wang, Y., Chen, J., Tao, J., Tian, G., Wu, S., Liu, W., Cui, Q., Geng, B., Zhang, W., Weldon, R., Auguste, K., Yang, L., Liu, X., Chen, L., Yang, X., Zhu, B., & Cai, J. (2017). Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome, 5(1), Article 14. https://doi.org/10.1186/s40168-016-0222-x
- Yang, T., Santisteban, M. M., Rodriguez, V., Li, E., Ahmari, N., Carvajal, J. M., Zadeh, M., Gong, M., Qi, Y., Zubcevic, J., Sahay, B., Pepine, C. J., Raizada, M. K., & Mohamadzadeh, M. (2015). Gut dysbiosis is linked to hypertension. Hypertension, 65(6), 1331-1340. https://doi.org/10.1161/HYPERTENSIONAHA.115.05315
- Kanbay, M., Onal, E. M., Afsar, B., Dagel, T., Yerlikaya, A., Covic, A., & Vaziri, N. D. (2018). The crosstalk of gut microbiota and chronic kidney disease: role of inflammation, proteinuria, hypertension, and diabetes mellitus. International Urology and Nephrology, 50(8), 1453-1466. https://doi.org/10.1007/s11255-018-1873-2
- Silveira-Nunes, G., Durso, D. F., Jr, L., Cunha, E., Maioli, T. U., Vieira, A. T., Speziali, E., Corrêa-Oliveira, R., Martins-Filho, O. A., Teixeira-Carvalho, A., Franceschi, C., Rampelli, S., Turroni, S., Brigidi, P., & Faria, A. (2020). Hypertension Is Associated With Intestinal Microbiota Dysbiosis and Inflammation in a Brazilian Population. Frontiers in Pharmacology, 11, Article 258. https://doi.org/10.3389/fphar.2020.00258
- Jama, H. A., Kaye, D. M., & Marques, F. Z. (2019). The gut microbiota and blood pressure in experimental models. Current Opinion in Nephrology and Hypertension, 28(2), 97-104. https://doi.org/10.1097/MNH.0000000000000476
- Karbach, S. H., Schönfelder, T., Brandão, I., Wilms, E., Hörmann, N., Jäckel, S., Schüler, R., Finger, S., Knorr, M., Lagrange, J., Brandt, M., Waisman, A., Kossmann, S., Schäfer, K., Münzel, T., Reinhardt, C., & Wenzel, P. (2016). Gut Microbiota Promote Angiotensin II-Induced Arterial Hypertension and Vascular Dysfunction. Journal of the American Heart Association, 5(9), Article e003698. https://doi.org/10.1161/JAHA.116.003698
- Toral, M., Robles-Vera, I., de la Visitación, N., Romero, M., Yang, T., Sánchez, M., Gómez-Guzmán, M., Jiménez, R., Raizada, M. K., & Duarte, J. (2019). Critical Role of the Interaction Gut Microbiota - Sympathetic Nervous System in the Regulation of Blood Pressure. Frontiers in Physiology, 10, Article 231. https://doi.org/10.3389/fphys.2019.00231
- Santisteban, M. M., Qi, Y., Zubcevic, J., Kim, S., Yang, T., Shenoy, V., Cole-Jeffrey, C. T., Lobaton, G. O., Stewart, D. C., Rubiano, A., Simmons, C. S., Garcia-Pereira, F., Johnson, R. D., Pepine, C. J., & Raizada, M. K. (2017). Hypertension-Linked Pathophysiological Alterations in the Gut. Circulation Research, 120(2), 312-323. https://doi.org/10.1161/CIRCRESAHA.116.309006
- Adnan, S., Nelson, J. W., Ajami, N. J., Venna, V. R., Petrosino, J. F., Bryan, R. M., Jr., & Durgan, D. J. (2017). Alterations in the gut microbiota can elicit hypertension in rats. Physiological Genomics, 49(2), 96-104. https://doi.org/10.1152/physiolgenomics.00081.2016
- Nowiński, A., & Ufnal, M. (2018). Trimethylamine N-oxide: A harmful, protective or diagnostic marker in lifestyle diseases? Nutrition, 46, 7-12. https://doi.org/10.1016/j.nut.2017.08.001
- Cho, C. E., & Caudill, M. A. (2017). Trimethylamine-N-Oxide: Friend, Foe, or Simply Caught in the Cross-Fire? Trends in Endocrinology & Metabolism, 28(2), 121-130. https://doi.org/10.1016/j.tem.2016.10.005
- Tang, W. H., & Hazen, S. L. (2017). Microbiome, trimethylamine N-oxide, and cardiometabolic disease. Translational Research, 179, 108-115. https://doi.org/10.1016/j.trsl.2016.07.007
- Ge, X., Zheng, L., Zhuang, R., Yu, P., Xu, Z., Liu, G., Xi, X., Zhou, X., & Fan, H. (2020). The Gut Microbial Metabolite Trimethylamine N-Oxide and Hypertension Risk: A Systematic Review and Dose-Response Meta-analysis. Advances in Nutrition, 11(1), 66-76. https://doi.org/10.1093/advances/nmz064
- Li, Z., Wu, Z., Yan, J., Liu, H., Liu, Q., Deng, Y., Ou, C., & Chen, M. (2019). Gut microbe-derived metabolite trimethylamine N-oxide induces cardiac hypertrophy and fibrosis. Laboratory Investigation, 99(3), 346-357. https://doi.org/10.1038/s41374-018-0091-y
- Huc, T., Drapala, A., Gawrys, M., Konop, M., Bielinska, K., Zaorska, E., Samborowska, E., Wyczalkowska-Tomasik, A., Pączek, L., Dadlez, M., & Ufnal, M. (2018). Chronic, low-dose TMAO treatment reduces diastolic dysfunction and heart fibrosis in hypertensive rats. American journal of Physiology-Heart and Circulatory Physiology, 315(6), H1805-H1820. https://doi.org/10.1152/ajpheart.00536.2018
- Chambers, E. S., Preston, T., Frost, G., & Morrison, D. J. (2018). Role of Gut Microbiota-Generated Short-Chain Fatty Acids in Metabolic and Cardiovascular Health. Current Nutrition Reports, 7(4), 198-206. https://doi.org/10.1007/s13668-018-0248-8
- Louis, P., & Flint, H. J. (2017). Formation of propionate and butyrate by the human colonic microbiota. Environmental Microbiology, 19(1), 29-41. https://doi.org/10.1111/1462-2920.13589
- Miyamoto, J., Kasubuchi, M., Nakajima, A., Irie, J., Itoh, H., & Kimura, I. (2016). The role of short-chain fatty acid on blood pressure regulation. Current Opinion in Nephrology and Hypertension, 25(5), 379-383. https://doi.org/10.1097/MNH.0000000000000246
- Chen, Y., Xu, C., Huang, R., Song, J., Li, D., & Xia, M. (2018). Butyrate from pectin fermentation inhibits intestinal cholesterol absorption and attenuates atherosclerosis in apolipoprotein E-deficient mice. The Journal of Nutritional Biochemistry, 56, 175-182. https://doi.org/10.1016/j.jnutbio.2018.02.011
- Liu, H., Wang, J., He, T., Becker, S., Zhang, G., Li, D., & Ma, X. (2018). Butyrate: A Double-Edged Sword for Health? Advances in Nutrition, 9(1), 21-29. https://doi.org/10.1093/advances/nmx009
- Wang, L., Zhu, Q., Lu, A., Liu, X., Zhang, L., Xu, C., Liu, X., Li, H., & Yang, T. (2017). Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of renal (pro)renin receptor and intrarenal renin-angiotensin system. Journal of Hypertension, 35(9), 1899-1908. https://doi.org/10.1097/HJH.0000000000001378
- Yang, T., Magee, K. L., Colon-Perez, L. M., Larkin, R., Liao, Y. S., Balazic, E., Cowart, J. R., Arocha, R., Redler, T., Febo, M., Vickroy, T., Martyniuk, C. J., Reznikov, L. R., & Zubcevic, J. (2019). Impaired butyrate absorption in the proximal colon, low serum butyrate and diminished central effects of butyrate on blood pressure in spontaneously hypertensive rats. Acta Physiologica, 226(2), Article e13256. https://doi.org/10.1111/apha.13256
- Gomez-Arango, L. F., Barrett, H. L., McIntyre, H. D., Callaway, L. K., Morrison, M., Dekker Nitert, M., & SPRING Trial Group. (2016). Increased Systolic and Diastolic Blood Pressure Is Associated With Altered Gut Microbiota Composition and Butyrate Production in Early Pregnancy. Hypertension, 68(4), 974-981. https://doi.org/10.1161/HYPERTENSIONAHA.116.07910
- Maßberg, D., & Hatt, H. (2018). Human Olfactory Receptors: Novel Cellular Functions Outside of the Nose. Physiological Reviews, 98(3), 1739-1763. https://doi.org/10.1152/physrev.00013.2017
- Natarajan, N., Hori, D., Flavahan, S., Steppan, J., Flavahan, N. A., Berkowitz, D. E., & Pluznick, J. L. (2016). Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41. Physiological Genomics, 48(11), 826-834. https://doi.org/10.1152/physiolgenomics.00089.2016
- Natarajan, N., & Pluznick, J. L. (2016). Olfaction in the kidney: 'smelling' gut microbial metabolites. Experimental Physiology, 101(4), 478-481. https://doi.org/10.1113/EP085285
- Pluznick, J. L. (2017). Microbial Short-Chain Fatty Acids and Blood Pressure Regulation. Current Hypertension Reports, 19(4), Article 25. https://doi.org/10.1007/s11906-017-0722-5
- Onyszkiewicz, M., Gawrys-Kopczynska, M., Konopelski, P., Aleksandrowicz, M., Sawicka, A., Koźniewska, E., Samborowska, E., & Ufnal, M. (2019). Butyric acid, a gut bacteria metabolite, lowers arterial blood pressure via colon-vagus nerve signaling and GPR41/43 receptors. Pflügers Archiv - European Journal of Physiology, 471(11-12), 1441-1453. https://doi.org/10.1007/s00424-019-02322-y
- Di Lorenzo, F., De Castro, C., Silipo, A., & Molinaro, A. (2019). Lipopolysaccharide structures of Gram-negative populations in the gut microbiota and effects on host interactions. FEMS Microbiology Reviews, 43(3), 257-272. https://doi.org/10.1093/femsre/fuz002
- Moludi, J., Maleki, V., Jafari-Vayghyan, H., Vaghef-Mehrabany, E., & Alizadeh, M. (2020). Metabolic endotoxemia and cardiovascular disease: A systematic review about potential roles of prebiotics and probiotics. Clinical and Experimental Pharmacology and Physiology, 47(6), 927-939. https://doi.org/10.1111/1440-1681.13250
- Aune, D., Giovannucci, E., Boffetta, P., Fadnes, L. T., Keum, N., Norat, T., Greenwood, D. C., Riboli, E., Vatten, L. J., & Tonstad, S. (2017). Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality-a systematic review and dose-response meta-analysis of prospective studies. International Journal of Epidemiology, 46(3), 1029-1056. https://doi.org/10.1093/ije/dyw319
- Marques, F. Z., Nelson, E., Chu, P. Y., Horlock, D., Fiedler, A., Ziemann, M., Tan, J. K., Kuruppu, S., Rajapakse, N. W., El-Osta, A., Mackay, C. R., & Kaye, D. M. (2017). High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice. Circulation, 135(10), 964-977. https://doi.org/10.1161/CIRCULATIONAHA.116.024545
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