arthyperАртериальная гипертензия"Arterial’naya Gipertenziya" ("Arterial Hypertension")1607-419X2411-8524Antihypertensive League10.18705/1607-419X-2019-25-5-460-466arthyper-1879Research ArticleСтатьиArticlesАртериальная гипертензия: роль микробиоты кишечникаArterial hypertension: The role of gut microbiotaБаранцевичН. Е.BarantsevichN. E.

Баранцевич Наталья Евгеньевна — научный сотрудник научно-исследовательской лаборатории внутрибольничных инфекций.

Natalia E. Barantsevich - MD, Researcher, Unit of Nosocomial Infections.

St Petersburg

КонрадиА. О.KonradiA. O.

Конради Александра Олеговна—доктор медицинских наук, профессор, член-корреспондент РАН, заместитель генерального директора по научной работе.

Aleksandra O. Konradi - MD, PhD, DSc, Professor, Deputy Director General on Research.

St Petersburg

БаранцевичЕ. П.BarantsevichE. P.

Баранцевич Елена Петровна — доктор медицинских наук, заведующая научно-исследовательской лабораторией внутрибольничных инфекций.

Ул. Аккуратова, д. 2, Санкт-Петербург, 197341

Elena P. Barantsevich - MD, PhD, DSc, Head, Unit of Nosocomial Infections.

2 Akkuratov street, St Petersburg, 197341

lenabara2003@inbox.ruФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр имени В. А. Алмазова» Министерства здравоохранения Российской ФедерацииРоссияAlmazov National Medical Research CentreRussian Federation201929012020255460466Copyright © Баранцевич Н.Е., Конради А.О., Баранцевич Е.П., 20202020Баранцевич Н.Е., Конради А.О., Баранцевич Е.П.Barantsevich N.E., Konradi A.O., Barantsevich E.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://htn.almazovcentre.ru/jour/article/view/1879

Длительное время в патогенезе артериальной гипертензии (АГ) рассматривались преимущественно факторы, связанные с генетикой и эпигенетикой, окружающей средой и многочисленными нарушениями различных компонентов гомеостаза (вегетативная нервная система, иммунная система, ренин-ангиотензиновая система). Роль кишечной микробиоты как самостоятельного фактора, способного как благоприятствовать, так и противодействовать развитию АГ, получила признание относительно недавно. В обзоре представлены новые данные о влиянии кишечной бактериобиоты на развитие АГ, прямой регуляции артериального давления ее метаболитами, их влиянии на эпигенетические изменения, иммунитет и ренин-ангиотензин-альдостероновую систему.

Pathogenesis of arterial hypertension (HTN) was predominantly associated with genetics and epigenetics, environment and disturbances in homeostasis systems (autonomous nervous system, immunity, renin-angiotensin system) for a long time. Gut microbiota has recently emerged as a self-controlled factor contributing to or limiting the development of HTN. New data on the role of gut bacteria in the development of HTN, direct blood pressure regulation as well as impact on epigenetics, immunity and renin-angiotensin-aldosterone system of its metabolites are presented.

артериальная гипертензияпатогенезмикробиомдисбиозхроническое субклиническое воспалениемикроорганизмыиммунная системарецепторыкороткоцепочечные жирные кислоты (КЦЖК)hypertensionpathogenesismicrobiomechronic low-grade inflammationmicroorganismsimmune systemreceptorsshort chain fatty acids (SCFA)Исследование выполнялось при поддержке Гранта Президента Российской Федерации по государственной поддержке ведущих научных школ Российской Федерации НШ-5508.2018.7 (соглашение № 075-15-2019-161 от 23.05.2019)The study was supported by the Grant of the President of the Russian Federation for the Leading Scientific Schools of the Russian Federation НШ-5508.2018.7 (agreement № 075-15-2019-161, 23.05.2019)ReferencesWise IA, Charchar F J. Epigenetic modifications in essential hypertension. Int J Mol Sci. 2016;17(4):451. doi:10.3390/ijms17040451Wise IA, Charchar F J. Epigenetic modifications in essential hypertension. Int J Mol Sci. 2016;17(4):451. doi:10.3390/ijms17040451Ahn SY, Gupta C. Genetic programming of hypertension. Front Pediatr. 2017;5:285. doi:10.3389/fped.2017.00285Ahn SY, Gupta C. Genetic programming of hypertension. Front Pediatr. 2017;5:285. doi:10.3389/fped.2017.00285Aroor AR, Demarco VG, Jia G, Sun Z, Nistala R, Meinin-ger GA et al. The role of tissue Renin-Angiotensin aldosterone system in the development of endothelial dysfunction and arterial stiffness. Front Endocrinol. 2013;4:161. doi:10.3389/fendo.2013.00161Aroor AR, Demarco VG, Jia G, Sun Z, Nistala R, Meinin-ger GA et al. The role of tissue Renin-Angiotensin aldosterone system in the development of endothelial dysfunction and arterial stiffness. Front Endocrinol. 2013;4:161. doi:10.3389/fendo.2013.00161Young CN, Davisson RL. Angiotensin-II, the brain, and hypertension: an update. Hypertension. 2015;66(5):920-926.Young CN, Davisson RL. Angiotensin-II, the brain, and hypertension: an update. Hypertension. 2015;66(5):920-926.Mancia G, Grassi G. The autonomic nervous system and hypertension. Circ Res. 2014;114(11):1804-1814. doi:10.1161/HYPERTENSIONAHA.115.03624Mancia G, Grassi G. The autonomic nervous system and hypertension. Circ Res. 2014;114(11):1804-1814. doi:10.1161/HYPERTENSIONAHA.115.03624Harrison DG. The immune system in hypertension. Trans Am Clin Climatol Assoc. 2014;125:130-138. doi:10.1161/HYPERTENSIONAHA.115.03624Harrison DG. The immune system in hypertension. Trans Am Clin Climatol Assoc. 2014;125:130-138. doi:10.1161/HYPERTENSIONAHA.115.03624Zubcevic J, Richards EM, Yang T, Kim S, Sumners C, Pepine CJ et al. Impaired autonomic nervous system-microbiome circuit in hypertension. Circ Res. 2019;125(1): 104-116. doi:10.1161/CIRCRESAHA.119.313965Zubcevic J, Richards EM, Yang T, Kim S, Sumners C, Pepine CJ et al. Impaired autonomic nervous system-microbiome circuit in hypertension. Circ Res. 2019;125(1): 104-116. doi:10.1161/CIRCRESAHA.119.313965Roager HM, Licht TR, Poulsen SK, Larsen TM, Bahla MI. Microbial enterotypes, inferred by the prevotella-to-bacteroides ratio, remained stable during a 6-month randomized controlled diet intervention with the new Nordic diet. Appl Environ Microbiol. 2014;80(3):1142-1149. doi:10.1128/AEM.03549-13Roager HM, Licht TR, Poulsen SK, Larsen TM, Bahla MI. Microbial enterotypes, inferred by the prevotella-to-bacteroides ratio, remained stable during a 6-month randomized controlled diet intervention with the new Nordic diet. Appl Environ Microbiol. 2014;80(3):1142-1149. doi:10.1128/AEM.03549-13Yang T, Santisteban MM, Rodriguez V, Li E, Ahmari N, Car-vajal JM et al. Gut dysbiosis is linked to hypertension. Hypertension. 2015;65(6): 1331-1340. doi:10.1161/HYPERTENSIONAHA.115.05315Yang T, Santisteban MM, Rodriguez V, Li E, Ahmari N, Car-vajal JM et al. Gut dysbiosis is linked to hypertension. Hypertension. 2015;65(6): 1331-1340. doi:10.1161/HYPERTENSIONAHA.115.05315Mell B, Jala VR, Mathew AV, Byun J, Waghulde H, Zhang Y et al. Evidence for a link between gut microbiota and hypertension in the Dahl rat. Physiol Genom. 2015;47(6): 187-197. doi:10.1152/physiolgenomics.00136.2014Mell B, Jala VR, Mathew AV, Byun J, Waghulde H, Zhang Y et al. Evidence for a link between gut microbiota and hypertension in the Dahl rat. Physiol Genom. 2015;47(6): 187-197. doi:10.1152/physiolgenomics.00136.2014Durgan 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(2):469-474. doi:10.1161/HYPERTENSIONAHA.115.06672Durgan 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(2):469-474. doi:10.1161/HYPERTENSIONAHA.115.06672Li 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(1):14. doi:10.1186/s40168-016-0222-xLi 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(1):14. doi:10.1186/s40168-016-0222-xSantisteban MM, Qi Y, Zubcevic J, Kim S, Yang T, Shenoy V et al. Hypertension-linked pathophysiological alterations in the gut. Circ Res. 2017;120(2):312-323. doi:10.1161/CIRCRESAHA.116.309006Santisteban MM, Qi Y, Zubcevic J, Kim S, Yang T, Shenoy V et al. Hypertension-linked pathophysiological alterations in the gut. Circ Res. 2017;120(2):312-323. doi:10.1161/CIRCRESAHA.116.309006Wilck 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(7682):585-589. doi:10.1038/nature24628Wilck 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(7682):585-589. doi:10.1038/nature24628Toral M, Robles-Vera I, de la Visitacion N, Romero M, Yang T, Sanchez M et al. Critical role of interaction gut microbiota — sympathetic nervous system in regulation of blood pressure. Front Physiol. 2019;10:231. doi:10.3389/fphys.2019.00231Toral M, Robles-Vera I, de la Visitacion N, Romero M, Yang T, Sanchez M et al. Critical role of interaction gut microbiota — sympathetic nervous system in regulation of blood pressure. Front Physiol. 2019;10:231. doi:10.3389/fphys.2019.00231Yang T, Richards EM, Pepine CJ, Raizada MK. The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease. Nat Rev Nephrol. 2018;14(7):442-456. doi:10.1038/s41581-018-0018-2Yang T, Richards EM, Pepine CJ, Raizada MK. The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease. Nat Rev Nephrol. 2018;14(7):442-456. doi:10.1038/s41581-018-0018-2Pluznick 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(11):4410-4415. doi:10.1073/pnas.1215927110Pluznick 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(11):4410-4415. doi:10.1073/pnas.1215927110Natarajan N, Hori D, Flavahan S, Steppan J, Flavahan NA, Berkowitz DE et al. Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41. Physiol Genom. 2016;48(11):826-834. doi:10.1152/physio-lgenomics.00089.2016Natarajan N, Hori D, Flavahan S, Steppan J, Flavahan NA, Berkowitz DE et al. Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41. Physiol Genom. 2016;48(11):826-834. doi:10.1152/physio-lgenomics.00089.2016Marques 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(10):964-977. doi:10.1161/CIRCULATIONAHA.116.024545Marques 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(10):964-977. doi:10.1161/CIRCULATIONAHA.116.024545Aleixandre A, Miguel M. Dietary fiber and blood pressure control. Food Fund. 2016;7(4):1864-1871. doi:10.1039/c5fo 00950bAleixandre A, Miguel M. Dietary fiber and blood pressure control. Food Fund. 2016;7(4):1864-1871. doi:10.1039/c5fo 00950bWhelton SP, Hyre AD, Pedersen B, Yi Y, Whelton PK, He J et al. Effect of dietary fiber intake on blood pressure: a metaanalysis of randomized, controlled clinical trials. J Hypertens. 2005;23(3):475-481.Whelton SP, Hyre AD, Pedersen B, Yi Y, Whelton PK, He J et al. Effect of dietary fiber intake on blood pressure: a metaanalysis of randomized, controlled clinical trials. J Hypertens. 2005;23(3):475-481.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 (4):897-903. doi:10.1161/HYPERTENSIONAHA.114.03469Khalesi 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 (4):897-903. doi:10.1161/HYPERTENSIONAHA.114.03469Qi 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;201:157-158. doi:10.1016/j.ijcard.2015.07.078Qi 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;201:157-158. doi:10.1016/j.ijcard.2015.07.078Jose PA, Raj D. Gut microbiota in hypertension. Curr Opin Nephrol Hypertens. 2015;24(5):403-409. doi:10.1097/MNH.0000000000000149Jose PA, Raj D. Gut microbiota in hypertension. Curr Opin Nephrol Hypertens. 2015;24(5):403-409. doi:10.1097/MNH.0000000000000149Schlaich MP, Lambert E, Kaye DM, Krozowski Z, Campbell DJ, Lambert G et al. Sympathetic augmentation in hypertension: role of nerve firing, norepinephrine reuptake, and angiotensin neuromodulation. Hypertension. 2004;43(2):169-175.Schlaich MP, Lambert E, Kaye DM, Krozowski Z, Campbell DJ, Lambert G et al. Sympathetic augmentation in hypertension: role of nerve firing, norepinephrine reuptake, and angiotensin neuromodulation. Hypertension. 2004;43(2):169-175.Ley RE, Tumbaugh PJ, Klein S, Gordon JI. Microbial ecology: Human gut microbes associated with obesity. Nature. 2006;444(7122):1022-1023.Ley RE, Tumbaugh PJ, Klein S, Gordon JI. Microbial ecology: Human gut microbes associated with obesity. Nature. 2006;444(7122):1022-1023.Wenzel P, Knorr M, Kossmann S, Stratmann J, Hausding M, Schuhmacher S et al. Lysozyme M-positive monocytes mediate angiotensin II-induced arterial hypertension and vascular dysfunction. Circulation. 2011;124(12):1370-1381. doi:10.1161/CIRCULATIONAHA.l11.034470Wenzel P, Knorr M, Kossmann S, Stratmann J, Hausding M, Schuhmacher S et al. Lysozyme M-positive monocytes mediate angiotensin II-induced arterial hypertension and vascular dysfunction. Circulation. 2011;124(12):1370-1381. doi:10.1161/CIRCULATIONAHA.l11.034470Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S et al. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med. 2007; 204(10):2449-2460.Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S et al. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med. 2007; 204(10):2449-2460.Chan CT, Sobey CG, Lieu M, Ferens D, Kett MM, Diep Henry et al. Obligatory role for b cells in the development of angiotensin II-dependent hypertension. Hypertension. 2015;66:1023-1033.Chan CT, Sobey CG, Lieu M, Ferens D, Kett MM, Diep Henry et al. Obligatory role for b cells in the development of angiotensin II-dependent hypertension. Hypertension. 2015;66:1023-1033.Pedrinelli R, Dell’Omo G, Di Bello V, Pellegrini G, Pucci L, Del Prato S et al. Low-grade inflammation and microalbuminuria in hypertension. Arterioscler Thromb Vasc Biol. 2004;24(12):2414-2419.Pedrinelli R, Dell’Omo G, Di Bello V, Pellegrini G, Pucci L, Del Prato S et al. Low-grade inflammation and microalbuminuria in hypertension. Arterioscler Thromb Vasc Biol. 2004;24(12):2414-2419.Costello-White R, Ryff CD, Coe CL. Aging and low-grade inflammation reduce renal function in middle-aged and older adults in Japan and the USA. Age. 2015;37(4):9808. doi:10.1007/s11357-015-9808-7Costello-White R, Ryff CD, Coe CL. Aging and low-grade inflammation reduce renal function in middle-aged and older adults in Japan and the USA. Age. 2015;37(4):9808. doi:10.1007/s11357-015-9808-7Santisteban MM, Ahmari N, Carvajal JM, Zingler MB, Qi Y, Kim S et al. Involvement of bone marrow cells and neuroinflammation in hypertension. Circ Res. 2015;117(2):178-191. doi:10.1161/CIRCRESAHA.117.305853Santisteban MM, Ahmari N, Carvajal JM, Zingler MB, Qi Y, Kim S et al. Involvement of bone marrow cells and neuroinflammation in hypertension. Circ Res. 2015;117(2):178-191. doi:10.1161/CIRCRESAHA.117.305853Callen IR, Limarzi LR. Blood and bone marrow studies in renal diseases. Am J Clin Pathol. 1950;20(1):3-23.Callen IR, Limarzi LR. Blood and bone marrow studies in renal diseases. Am J Clin Pathol. 1950;20(1):3-23.Jung C, Hugot JP, Barreau F. Peyer’s patches: the immune sensors of the intestine. Int J Inflam. 2010;2010:823710. doi:10.4061/2010/823710Jung C, Hugot JP, Barreau F. Peyer’s patches: the immune sensors of the intestine. Int J Inflam. 2010;2010:823710. doi:10.4061/2010/823710Wu IW, Hsu KH, Lee CC, Sun CY, Hsu HJ, Tsai CJ et al. p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease. Nephrol Dial Transplant. 2011;26(3):938-947. doi:10.1093/ndt/gfq580Wu IW, Hsu KH, Lee CC, Sun CY, Hsu HJ, Tsai CJ et al. p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease. Nephrol Dial Transplant. 2011;26(3):938-947. doi:10.1093/ndt/gfq580Lin CJ, Chen HH, Pan CF, Chuang CK, Wang TJ, Sun FJ et al. p-Cresylsulfate and indoxyl sulfate level at different stages of chronic kidney disease. J Clin Lab Anal. 2011;25(3):191-197. doi:10.1002/jcla.20456Lin CJ, Chen HH, Pan CF, Chuang CK, Wang TJ, Sun FJ et al. p-Cresylsulfate and indoxyl sulfate level at different stages of chronic kidney disease. J Clin Lab Anal. 2011;25(3):191-197. doi:10.1002/jcla.20456Magnusson M, Magnusson KE, Sundqvist T, Denneberg T. Increased intestinal permeability to differently sized polyethylene glycols in uremic rats: effects of low- and high-protein diets. Nephron. 1990;56(3):306-311.Magnusson M, Magnusson KE, Sundqvist T, Denneberg T. Increased intestinal permeability to differently sized polyethylene glycols in uremic rats: effects of low- and high-protein diets. Nephron. 1990;56(3):306-311.Magnusson M, Magnusson KE, Sundqvist T, Denneberg T. Impaired intestinal barrier function measured by differently sized polyethylene glycols in patients with chronic renal failure. Gut. 1991;32(7):754-759.Magnusson M, Magnusson KE, Sundqvist T, Denneberg T. Impaired intestinal barrier function measured by differently sized polyethylene glycols in patients with chronic renal failure. Gut. 1991;32(7):754-759.de Almeida Duarte JB, de Aguilar-Nascimento JE, Nascimento M, Nochi RJ. Bacterial translocation in experimental uremia. Urol Res. 2004;32(4):266-270.de Almeida Duarte JB, de Aguilar-Nascimento JE, Nascimento M, Nochi RJ. Bacterial translocation in experimental uremia. Urol Res. 2004;32(4):266-270.Wang F, Jiang H, Shi K, Ren Y, Zhang P, Cheng S et al. Gut bacterial translocation is associated with microinflammation in end-stage renal disease patients. Nephrology. 2012;17(8):733-738. doi:10.1111/j.1440-1797.2012.01647.xWang F, Jiang H, Shi K, Ren Y, Zhang P, Cheng S et al. Gut bacterial translocation is associated with microinflammation in end-stage renal disease patients. Nephrology. 2012;17(8):733-738. doi:10.1111/j.1440-1797.2012.01647.xShi K, Wang F, Jiang H, Liu H, Wei M, Wang Z et al. Gut bacterial translocation may aggravate microinflammation in hemodialysis patients. Dig Dis Sci. 2014;59(9):2109-2117. doi:10.1007/s10620-014-3202-7Shi K, Wang F, Jiang H, Liu H, Wei M, Wang Z et al. Gut bacterial translocation may aggravate microinflammation in hemodialysis patients. Dig Dis Sci. 2014;59(9):2109-2117. doi:10.1007/s10620-014-3202-7Ito S, Yoshida M. Protein-bound uremic toxins: new culprits of cardiovascular events in chronic kidney disease patients. Toxins. 2014;6(2):665-678. doi:10.3390/toxins6020665Ito S, Yoshida M. Protein-bound uremic toxins: new culprits of cardiovascular events in chronic kidney disease patients. Toxins. 2014;6(2):665-678. doi:10.3390/toxins6020665Sun CY, Chang SC, Wu MS. Uremic toxins induce kidney fibrosis by activating intrarenal renin-angiotensin-aldosterone system associated epithelial-to-mesenchymal transition. PLoS ONE. 2012;7(3):e34026. doi:10.1371/journal.pone.0034026Sun CY, Chang SC, Wu MS. Uremic toxins induce kidney fibrosis by activating intrarenal renin-angiotensin-aldosterone system associated epithelial-to-mesenchymal transition. PLoS ONE. 2012;7(3):e34026. doi:10.1371/journal.pone.0034026Tang WHW, Hazen SL. Microbiome, Trimethylamine N-Oxide (TMAO), and cardiometabolic disease. Transl Res. 2017;179:108-115. doi:10.1016/j.trsl.2016.07.007Tang WHW, Hazen SL. Microbiome, Trimethylamine N-Oxide (TMAO), and cardiometabolic disease. Transl Res. 2017;179:108-115. doi:10.1016/j.trsl.2016.07.007Cho CE, Caudill MA. Trimethylamine-N-Oxide: friend, foe, or simply caught in the cross-fire? Trends Endocrinol Metab. 2017;28(2):121-130. doi:10.1016/j.tem.2016.10.005Cho CE, Caudill MA. Trimethylamine-N-Oxide: friend, foe, or simply caught in the cross-fire? Trends Endocrinol Metab. 2017;28(2):121-130. doi:10.1016/j.tem.2016.10.005Scheppach W. Effects of short chain fatty acids on gut morphology and function. Gut. 1994;35 (1Suppl): S35-38.Scheppach W. Effects of short chain fatty acids on gut morphology and function. Gut. 1994;35 (1Suppl): S35-38.SirichTL, PlummerNS, Gardner CD, HostetterTH, MeyerTW. Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients. Clin J Am Soc Nephrol. 2014;9(9): 1603-1610. doi:10.2215/CJN.00490114SirichTL, PlummerNS, Gardner CD, HostetterTH, MeyerTW. Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients. Clin J Am Soc Nephrol. 2014;9(9): 1603-1610. doi:10.2215/CJN.00490114Andrade-Oliveira V,Amano MT, Correa-Costa M, CastoldiA, Felizardo RJ, de Almeida DC et al. Gut bacteriaproducts prevent AKI induced by ischemia-reperfusion. J Am Soc Nephrol. 2015;26 (8):1877-1888. doi:10.1681/ASN.2014030288Andrade-Oliveira V,Amano MT, Correa-Costa M, CastoldiA, Felizardo RJ, de Almeida DC et al. Gut bacteriaproducts prevent AKI induced by ischemia-reperfusion. J Am Soc Nephrol. 2015;26 (8):1877-1888. doi:10.1681/ASN.2014030288Ma J, Li H. The role ofgut microbiota in atherosclerosis and hypertension. Front Pharmacol. 2018;9:1082. doi:10.3389/fphar.2018.01082Ma J, Li H. The role ofgut microbiota in atherosclerosis and hypertension. Front Pharmacol. 2018;9:1082. doi:10.3389/fphar.2018.01082Everard A, Cani PD. Diabetes, obesity and gut microbiota. Best Pract Res Clin Gastroenterol. 2013;27(1):73-83. doi:10.1016/j.bpg.2013.03.007Everard A, Cani PD. Diabetes, obesity and gut microbiota. Best Pract Res Clin Gastroenterol. 2013;27(1):73-83. doi:10.1016/j.bpg.2013.03.007Blake GJ, Rifai N, Buring JE, Ridker PM. Blood pressure, C-reactive protein, and risk of future cardiovascular events. Circulation. 2003;108(24):2993-2999.Blake GJ, Rifai N, Buring JE, Ridker PM. Blood pressure, C-reactive protein, and risk of future cardiovascular events. Circulation. 2003;108(24):2993-2999.Canani RB, Costanzo MD, Leone L, Pedata M, Meli R, Calignano A. Potential beneficial effectsof butyrate in intestinal and extraintestinal diseases. World J Gastroenterol. 2011;17(12):1519-1528. doi:10.3748/wjg.v17.i12.1519Canani RB, Costanzo MD, Leone L, Pedata M, Meli R, Calignano A. Potential beneficial effectsof butyrate in intestinal and extraintestinal diseases. World J Gastroenterol. 2011;17(12):1519-1528. doi:10.3748/wjg.v17.i12.1519Vieira EL, Leonel AJ, Sad AP, Beltrao NR, Costa TF, Ferreira TM. Oral administration of sodiumbutyrate attenuates inflammation and mucosal lesion in experimentalacute ulcerative colitis. J Nutr Biochem. 2012;23(5):430-436. doi:10.1016/j.jnutbio.2011.01.007Vieira EL, Leonel AJ, Sad AP, Beltrao NR, Costa TF, Ferreira TM. Oral administration of sodiumbutyrate attenuates inflammation and mucosal lesion in experimentalacute ulcerative colitis. J Nutr Biochem. 2012;23(5):430-436. doi:10.1016/j.jnutbio.2011.01.007Richards EM, Pepine CJ, Raizada MK, Kim S. The gut, its microbiome, and hypertension. Curr Hypertens Rep. 2017;19 (4):36. doi:10.1007/s11906-017-0734-1Richards EM, Pepine CJ, Raizada MK, Kim S. The gut, its microbiome, and hypertension. Curr Hypertens Rep. 2017;19 (4):36. doi:10.1007/s11906-017-0734-1

The authors declare that there are no conflicts of interest present.