Obstructive Sleep Apnea-Induced Hypertension: Role of the Gut Microbiota

go back to reference Drager LF, Genta PR, Pedrosa RP, Nerbass FB, Gonzaga CC, Krieger EM, Lorenzi-Filho G. Characteristics and predictors of obstructive sleep apnea in patients with systemic hypertension. Am J Cardiol. 2010;105:1135–9. doi:10.1016/j.amjcard.2009.12.017.CrossRefPubMed Drager LF, Genta PR, Pedrosa RP, Nerbass FB, Gonzaga CC, Krieger EM, Lorenzi-Filho G. Characteristics and predictors of obstructive sleep apnea in patients with systemic hypertension. Am J Cardiol. 2010;105:1135–9. doi:10.​1016/​j.​amjcard.​2009.​12.​017.CrossRefPubMed

go back to reference Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, Daniels S, Floras JS, Hunt CE, Olson LJ, Pickering TG, Russell R, Woo M, Young T, American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, American Heart Association Stroke Council, American Heart Association Council on Cardiovascular Nursing, American College of Cardiology Foundation. Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation scientific statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on sleep disorders research (National Institutes of Health). Circulation. 2008;118:1080–111. doi:10.1161/CIRCULATIONAHA.107.189375.CrossRefPubMed Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, Daniels S, Floras JS, Hunt CE, Olson LJ, Pickering TG, Russell R, Woo M, Young T, American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, American Heart Association Stroke Council, American Heart Association Council on Cardiovascular Nursing, American College of Cardiology Foundation. Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation scientific statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on sleep disorders research (National Institutes of Health). Circulation. 2008;118:1080–111. doi:10.​1161/​CIRCULATIONAHA.​107.​189375.CrossRefPubMed

go back to reference Javaheri S, Barbe F, Campos-Rodriguez F, Dempsey JA, Khayat R, Javaheri S, Malhotra A, Martinez-Garcia MA, Mehra R, Pack AI, Polotsky VY, Redline S, Somers VK. Sleep apnea: types, mechanisms, and clinical cardiovascular consequences. J Am Coll Cardiol. 2017;69:841–58.CrossRefPubMed Javaheri S, Barbe F, Campos-Rodriguez F, Dempsey JA, Khayat R, Javaheri S, Malhotra A, Martinez-Garcia MA, Mehra R, Pack AI, Polotsky VY, Redline S, Somers VK. Sleep apnea: types, mechanisms, and clinical cardiovascular consequences. J Am Coll Cardiol. 2017;69:841–58.CrossRefPubMed

go back to reference Dempsey JA, Veasey SC, Morgan BJ, O'Donnell CP. Pathophysiology of sleep apnea. Physiol Rev. 2010;90:47–112. doi:10.1152/physrev.00043.2008.CrossRefPubMedPubMedCentral Dempsey JA, Veasey SC, Morgan BJ, O'Donnell CP. Pathophysiology of sleep apnea. Physiol Rev. 2010;90:47–112. doi:10.​1152/​physrev.​00043.​2008.CrossRefPubMedPubMedCentral

go back to reference Durgan DJ, Bryan Jr RM. Cerebrovascular consequences of obstructive sleep apnea. J Am Heart Assoc. 2012;1:e000091. doi:10.1161/JAHA.111.000091.CrossRefPubMedPubMedCentral Durgan DJ, Bryan Jr RM. Cerebrovascular consequences of obstructive sleep apnea. J Am Heart Assoc. 2012;1:e000091. doi:10.​1161/​JAHA.​111.​000091.CrossRefPubMedPubMedCentral

go back to reference Lavie P. Restless nights: understanding snoring and sleep apnea. New Haven: Yale University Press; 2003. Lavie P. Restless nights: understanding snoring and sleep apnea. New Haven: Yale University Press; 2003.

go back to reference Dickens C. The Pickwick papers. New York; 1868. Dickens C. The Pickwick papers. New York; 1868.

go back to reference Gastaut H, Tassinari CA, Duron B. Polygraphic study of the episodic diurnal and nocturnal (hypnic and respiratory) manifestations of the Pickwick syndrome. Brain Res. 1966;1:167–86.CrossRefPubMed Gastaut H, Tassinari CA, Duron B. Polygraphic study of the episodic diurnal and nocturnal (hypnic and respiratory) manifestations of the Pickwick syndrome. Brain Res. 1966;1:167–86.CrossRefPubMed

go back to reference Gastaut H, Duron B, Papy JJ, Tassinari C, Waltregny A. Comparative polygraphic study of the 24 hour cycle in Pickwickians, the obese and narcoleptics. Electroencephalogr Clin Neurophysiol. 1967;23:284.PubMed Gastaut H, Duron B, Papy JJ, Tassinari C, Waltregny A. Comparative polygraphic study of the 24 hour cycle in Pickwickians, the obese and narcoleptics. Electroencephalogr Clin Neurophysiol. 1967;23:284.PubMed

go back to reference Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328:1230–5. doi:10.1056/NEJM199304293281704.CrossRefPubMed Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328:1230–5. doi:10.​1056/​NEJM199304293281​704.CrossRefPubMed

go back to reference Kapur V, Strohl KP, Redline S, Iber C, O'Connor G, Nieto J. Underdiagnosis of sleep apnea syndrome in U.S. communities. Sleep Breath. 2002;6:49–54. doi:10.1007/s11325-002-0049-5.CrossRefPubMed Kapur V, Strohl KP, Redline S, Iber C, O'Connor G, Nieto J. Underdiagnosis of sleep apnea syndrome in U.S. communities. Sleep Breath. 2002;6:49–54. doi:10.​1007/​s11325-002-0049-5.CrossRefPubMed

go back to reference Narkiewicz K, van de Borne PJ, Montano N, Dyken ME, Phillips BG, Somers VK. Contribution of tonic chemoreflex activation to sympathetic activity and blood pressure in patients with obstructive sleep apnea. Circulation. 1998;97:943–5.CrossRefPubMed Narkiewicz K, van de Borne PJ, Montano N, Dyken ME, Phillips BG, Somers VK. Contribution of tonic chemoreflex activation to sympathetic activity and blood pressure in patients with obstructive sleep apnea. Circulation. 1998;97:943–5.CrossRefPubMed

go back to reference Kasai T, Floras JS, Bradley TD. Sleep apnea and cardiovascular disease: a bidirectional relationship. Circulation. 2012;126:1495–510. doi:10.1161/CIRCULATIONAHA.111.070813.CrossRefPubMed Kasai T, Floras JS, Bradley TD. Sleep apnea and cardiovascular disease: a bidirectional relationship. Circulation. 2012;126:1495–510. doi:10.​1161/​CIRCULATIONAHA.​111.​070813.CrossRefPubMed

go back to reference Floras JS, Bradley TD. Treating obstructive sleep apnea: is there more to the story than 2 millimeters of mercury? Hypertension. 2007;50:289–91.CrossRefPubMed Floras JS, Bradley TD. Treating obstructive sleep apnea: is there more to the story than 2 millimeters of mercury? Hypertension. 2007;50:289–91.CrossRefPubMed

go back to reference Narkiewicz K, Pesek CA, Kato M, Phillips BG, Davison DE, Somers VK. Baroreflex control of sympathetic nerve activity and heart rate in obstructive sleep apnea. Hypertension. 1998;32:1039–43.CrossRefPubMed Narkiewicz K, Pesek CA, Kato M, Phillips BG, Davison DE, Somers VK. Baroreflex control of sympathetic nerve activity and heart rate in obstructive sleep apnea. Hypertension. 1998;32:1039–43.CrossRefPubMed

go back to reference Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995;96:1897–904. doi:10.1172/JCI118235S.CrossRefPubMedPubMedCentral Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995;96:1897–904. doi:10.​1172/​JCI118235S.CrossRefPubMedPubMedCentral

go back to reference Katragadda S, Xie A, Puleo D, Skatrud JB, Morgan BJ. Neural mechanism of the pressor response to obstructive and nonobstructive apnea. J Appl Physiol (1985). 1997;83:2048–54. Katragadda S, Xie A, Puleo D, Skatrud JB, Morgan BJ. Neural mechanism of the pressor response to obstructive and nonobstructive apnea. J Appl Physiol (1985). 1997;83:2048–54.

go back to reference Parati G, Lombardi C, Castagna F, Mattaliano P, Filardi PP, Agostoni P. Italian Society of Cardiology (SIC) Working Group on Heart Failure members. Heart failure and sleep disorders. Nat Rev Cardiol. 2016;13:389–403. doi:10.1038/nrcardio.2016.71.CrossRefPubMed Parati G, Lombardi C, Castagna F, Mattaliano P, Filardi PP, Agostoni P. Italian Society of Cardiology (SIC) Working Group on Heart Failure members. Heart failure and sleep disorders. Nat Rev Cardiol. 2016;13:389–403. doi:10.​1038/​nrcardio.​2016.​71.CrossRefPubMed

go back to reference Parati G, Lombardi C, Narkiewicz K. Sleep apnea: epidemiology, pathophysiology, and relation to cardiovascular risk. Am J Physiol Regul Integr Comp Physiol. 2007;293:R1671–83. doi:10.1152/ajpregu.00400.2007.CrossRefPubMed Parati G, Lombardi C, Narkiewicz K. Sleep apnea: epidemiology, pathophysiology, and relation to cardiovascular risk. Am J Physiol Regul Integr Comp Physiol. 2007;293:R1671–83. doi:10.​1152/​ajpregu.​00400.​2007.CrossRefPubMed

go back to reference Reutrakul S, Thakkinstian A, Anothaisintawee T, Chontong S, Borel AL, Perfect MM, Janovsky CC, Kessler R, Schultes B, Harsch IA, van Dijk M, Bouhassira D, Matejko B, Lipton RB, Suwannalai P, Chirakalwasan N, Schober AK, Knutson KL. Sleep characteristics in type 1 diabetes and associations with glycemic control: systematic review and meta-analysis. Sleep Med. 2016;23:26–45.CrossRefPubMed Reutrakul S, Thakkinstian A, Anothaisintawee T, Chontong S, Borel AL, Perfect MM, Janovsky CC, Kessler R, Schultes B, Harsch IA, van Dijk M, Bouhassira D, Matejko B, Lipton RB, Suwannalai P, Chirakalwasan N, Schober AK, Knutson KL. Sleep characteristics in type 1 diabetes and associations with glycemic control: systematic review and meta-analysis. Sleep Med. 2016;23:26–45.CrossRefPubMed

go back to reference Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL, Jones DW, Materson BJ, Oparil S, Wright Jr JT, Roccella EJ, National Heart, Lung, and Blood Institute, National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206–52. doi:10.1161/01.HYP.0000107251.49515.c2.CrossRefPubMed Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL, Jones DW, Materson BJ, Oparil S, Wright Jr JT, Roccella EJ, National Heart, Lung, and Blood Institute, National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206–52. doi:10.​1161/​01.​HYP.​0000107251.​49515.​c2.CrossRefPubMed

go back to reference Fatureto-Borges F, Lorenzi-Filho G, Drager LF. Effectiveness of continuous positive airway pressure in lowering blood pressure in patients with obstructive sleep apnea: a critical review of the literature. Integr Blood Press Control. 2016;9:43–7. doi:10.2147/IBPC.S70402.PubMedPubMedCentral Fatureto-Borges F, Lorenzi-Filho G, Drager LF. Effectiveness of continuous positive airway pressure in lowering blood pressure in patients with obstructive sleep apnea: a critical review of the literature. Integr Blood Press Control. 2016;9:43–7. doi:10.​2147/​IBPC.​S70402.PubMedPubMedCentral

go back to reference Pedrosa RP, Drager LF, Gonzaga CC, Sousa MG, de Paula LK, Amaro AC, Amodeo C, Bortolotto LA, Krieger EM, Bradley TD, Lorenzi-Filho G. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension. 2011;58:811–7. doi:10.1161/HYPERTENSIONAHA.111.179788.CrossRefPubMed Pedrosa RP, Drager LF, Gonzaga CC, Sousa MG, de Paula LK, Amaro AC, Amodeo C, Bortolotto LA, Krieger EM, Bradley TD, Lorenzi-Filho G. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension. 2011;58:811–7. doi:10.​1161/​HYPERTENSIONAHA.​111.​179788.CrossRefPubMed

go back to reference Logan AG, Perlikowski SM, Mente A, Tisler A, Tkacova R, Niroumand M, Leung RS, Bradley TD. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens. 2001;19:2271–7.CrossRefPubMed Logan AG, Perlikowski SM, Mente A, Tisler A, Tkacova R, Niroumand M, Leung RS, Bradley TD. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens. 2001;19:2271–7.CrossRefPubMed

go back to reference Young T, Palta M, Dempsey J, Peppard PE, Nieto FJ, Hla KM. Burden of sleep apnea: rationale, design, and major findings of the Wisconsin Sleep Cohort study. WMJ. 2009;108:246–9.PubMedPubMedCentral Young T, Palta M, Dempsey J, Peppard PE, Nieto FJ, Hla KM. Burden of sleep apnea: rationale, design, and major findings of the Wisconsin Sleep Cohort study. WMJ. 2009;108:246–9.PubMedPubMedCentral

go back to reference Young T, Peppard P, Palta M, Hla KM, Finn L, Morgan B, Skatrud J. Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med. 1997;157:1746–52.CrossRefPubMed Young T, Peppard P, Palta M, Hla KM, Finn L, Morgan B, Skatrud J. Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med. 1997;157:1746–52.CrossRefPubMed

go back to reference Hla KM, Young TB, Bidwell T, Palta M, Skatrud JB, Dempsey J. Sleep apnea and hypertension. A population-based study. Ann Intern Med. 1994;120:382–8.CrossRefPubMed Hla KM, Young TB, Bidwell T, Palta M, Skatrud JB, Dempsey J. Sleep apnea and hypertension. A population-based study. Ann Intern Med. 1994;120:382–8.CrossRefPubMed

go back to reference Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342:1378–84.CrossRefPubMed Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342:1378–84.CrossRefPubMed

go back to reference Kohler M, Smith D, Tippett V, Stradling JR. Predictors of long-term compliance with continuous positive airway pressure. Thorax. 2010;65:829–32. doi:10.1136/thx.2010.135848.CrossRefPubMed Kohler M, Smith D, Tippett V, Stradling JR. Predictors of long-term compliance with continuous positive airway pressure. Thorax. 2010;65:829–32. doi:10.​1136/​thx.​2010.​135848.CrossRefPubMed

go back to reference McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, Mediano O, Chen R, Drager LF, Liu Z, Chen G, Du B, McArdle N, Mukherjee S, Tripathi M, Billot L, Li Q, Lorenzi-Filho G, Barbe F, Redline S, Wang J, Arima H, Neal B, White DP, Grunstein RR, Zhong N, Anderson CS. SAVE investigators and coordinators. CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med. 2016;375:919–31. doi:10.1056/NEJMoa1606599.CrossRefPubMed McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, Mediano O, Chen R, Drager LF, Liu Z, Chen G, Du B, McArdle N, Mukherjee S, Tripathi M, Billot L, Li Q, Lorenzi-Filho G, Barbe F, Redline S, Wang J, Arima H, Neal B, White DP, Grunstein RR, Zhong N, Anderson CS. SAVE investigators and coordinators. CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med. 2016;375:919–31. doi:10.​1056/​NEJMoa1606599.CrossRefPubMed

go back to reference Dematteis M, Godin-Ribuot D, Arnaud C, Ribuot C, Stanke-Labesque F, Pepin JL, Levy P. Cardiovascular consequences of sleep-disordered breathing: contribution of animal models to understanding the human disease. ILAR J. 2009;50:262–81.CrossRefPubMed Dematteis M, Godin-Ribuot D, Arnaud C, Ribuot C, Stanke-Labesque F, Pepin JL, Levy P. Cardiovascular consequences of sleep-disordered breathing: contribution of animal models to understanding the human disease. ILAR J. 2009;50:262–81.CrossRefPubMed

go back to reference Farre R, Montserrat JM, Navajas D. Morbidity due to obstructive sleep apnea: insights from animal models. Curr Opin Pulm Med. 2008;14:530–6.CrossRefPubMed Farre R, Montserrat JM, Navajas D. Morbidity due to obstructive sleep apnea: insights from animal models. Curr Opin Pulm Med. 2008;14:530–6.CrossRefPubMed

go back to reference Fletcher EC, Brown DL. Nocturnal oxyhemoglobin desaturation following tracheostomy for obstructive sleep apnea. Am J Med. 1985;79:35–42.CrossRefPubMed Fletcher EC, Brown DL. Nocturnal oxyhemoglobin desaturation following tracheostomy for obstructive sleep apnea. Am J Med. 1985;79:35–42.CrossRefPubMed

go back to reference Fletcher EC, Lesske J, Culman J, Miller CC, Unger T. Sympathetic denervation blocks blood pressure elevation in episodic hypoxia. Hypertension. 1992;20:612–9.CrossRefPubMed Fletcher EC, Lesske J, Culman J, Miller CC, Unger T. Sympathetic denervation blocks blood pressure elevation in episodic hypoxia. Hypertension. 1992;20:612–9.CrossRefPubMed

go back to reference Allahdadi KJ, Walker BR, Kanagy NL. Augmented endothelin vasoconstriction in intermittent hypoxia-induced hypertension. Hypertension. 2005;45:705–9.CrossRefPubMed Allahdadi KJ, Walker BR, Kanagy NL. Augmented endothelin vasoconstriction in intermittent hypoxia-induced hypertension. Hypertension. 2005;45:705–9.CrossRefPubMed

go back to reference Bosc LV, Resta T, Walker B, Kanagy NL. Mechanisms of intermittent hypoxia induced hypertension. J Cell Mol Med. 2010;14:3–17. doi:10.1111/j.1582-4934.2009.00929.x.CrossRefPubMed Bosc LV, Resta T, Walker B, Kanagy NL. Mechanisms of intermittent hypoxia induced hypertension. J Cell Mol Med. 2010;14:3–17. doi:10.​1111/​j.​1582-4934.​2009.​00929.​x.CrossRefPubMed

go back to reference Kanagy NL, Walker BR, Nelin LD. Role of endothelin in intermittent hypoxia-induced hypertension. Hypertension. 2001;37:511–5.CrossRefPubMed Kanagy NL, Walker BR, Nelin LD. Role of endothelin in intermittent hypoxia-induced hypertension. Hypertension. 2001;37:511–5.CrossRefPubMed

go back to reference Dematteis M, Julien C, Guillermet C, Sturm N, Lantuejoul S, Mallaret M, Levy P, Gozal E. Intermittent hypoxia induces early functional cardiovascular remodeling in mice. Am J Respir Crit Care Med. 2008;177:227–35.CrossRefPubMed Dematteis M, Julien C, Guillermet C, Sturm N, Lantuejoul S, Mallaret M, Levy P, Gozal E. Intermittent hypoxia induces early functional cardiovascular remodeling in mice. Am J Respir Crit Care Med. 2008;177:227–35.CrossRefPubMed

go back to reference Neubauer JA. Invited review: Physiological and pathophysiological responses to intermittent hypoxia. J Appl Physiol (1985). 2001;90:1593–9. Neubauer JA. Invited review: Physiological and pathophysiological responses to intermittent hypoxia. J Appl Physiol (1985). 2001;90:1593–9.

go back to reference Crossland RF, Durgan DJ, Lloyd EE, Phillips SC, Reddy AK, Marrelli SP, Bryan Jr RM. A new rodent model for obstructive sleep apnea: effects on ATP-mediated dilations in cerebral arteries. Am J Physiol Regul Integr Comp Physiol. 2013;305:R334–42. doi:10.1152/ajpregu.00244.2013.CrossRefPubMedPubMedCentral Crossland RF, Durgan DJ, Lloyd EE, Phillips SC, Reddy AK, Marrelli SP, Bryan Jr RM. A new rodent model for obstructive sleep apnea: effects on ATP-mediated dilations in cerebral arteries. Am J Physiol Regul Integr Comp Physiol. 2013;305:R334–42. doi:10.​1152/​ajpregu.​00244.​2013.CrossRefPubMedPubMedCentral

go back to reference Durgan DJ, Crossland RF, Lloyd EE, Phillips SC, Bryan RM. Increased cerebrovascular sensitivity to endothelin-1 in a rat model of obstructive sleep apnea: a role for endothelin receptor B. J Cereb Blood Flow Metab. 2015;35:402–11. doi:10.1038/jcbfm.2014.214.CrossRefPubMed Durgan DJ, Crossland RF, Lloyd EE, Phillips SC, Bryan RM. Increased cerebrovascular sensitivity to endothelin-1 in a rat model of obstructive sleep apnea: a role for endothelin receptor B. J Cereb Blood Flow Metab. 2015;35:402–11. doi:10.​1038/​jcbfm.​2014.​214.CrossRefPubMed

go back to reference Drager LF, Jun JC, Polotsky VY. Metabolic consequences of intermittent hypoxia: relevance to obstructive sleep apnea. Best Pract Res Clin Endocrinol Metab. 2010;24:843–51. doi:10.1016/j.beem.2010.08.011.CrossRefPubMedPubMedCentral Drager LF, Jun JC, Polotsky VY. Metabolic consequences of intermittent hypoxia: relevance to obstructive sleep apnea. Best Pract Res Clin Endocrinol Metab. 2010;24:843–51. doi:10.​1016/​j.​beem.​2010.​08.​011.CrossRefPubMedPubMedCentral

go back to reference Pack AI, Gislason T. Obstructive sleep apnea and cardiovascular disease: a perspective and future directions. Prog Cardiovasc Dis. 2009;51:434–51. doi:10.1016/j.pcad.2009.01.002.CrossRefPubMed Pack AI, Gislason T. Obstructive sleep apnea and cardiovascular disease: a perspective and future directions. Prog Cardiovasc Dis. 2009;51:434–51. doi:10.​1016/​j.​pcad.​2009.​01.​002.CrossRefPubMed

go back to reference Baguet JP, Hammer L, Levy P, Pierre H, Launois S, Mallion JM, Pepin JL. The severity of oxygen desaturation is predictive of carotid wall thickening and plaque occurrence. Chest. 2005;128:3407–12.CrossRefPubMed Baguet JP, Hammer L, Levy P, Pierre H, Launois S, Mallion JM, Pepin JL. The severity of oxygen desaturation is predictive of carotid wall thickening and plaque occurrence. Chest. 2005;128:3407–12.CrossRefPubMed

go back to reference •• Durgan DJ, Ganesh BP, Cope JL, Ajami NJ, Phillips SC, Petrosino JF, Hollister EB, Bryan Jr RM. Role of the gut microbiome in obstructive sleep apnea-induced hypertension. Hypertension. 2016;67:469–74. doi:10.1161/HYPERTENSIONAHA.115.06672. This article demonstrated that dysbiosis induced by HFD and OSA contributed to hypertension in a rat model of OSA. Microbiota transplanted from OSA-induced hypertensive rats was capable of inducing hypertension in normotensive rats. PubMed •• Durgan DJ, Ganesh BP, Cope JL, Ajami NJ, Phillips SC, Petrosino JF, Hollister EB, Bryan Jr RM. Role of the gut microbiome in obstructive sleep apnea-induced hypertension. Hypertension. 2016;67:469–74. doi:10.​1161/​HYPERTENSIONAHA.​115.​06672. This article demonstrated that dysbiosis induced by HFD and OSA contributed to hypertension in a rat model of OSA. Microbiota transplanted from OSA-induced hypertensive rats was capable of inducing hypertension in normotensive rats. PubMed

go back to reference Mell B, Jala VR, Mathew AV, Byun J, Waghulde H, Zhang Y, Haribabu B, Vijay-Kumar M, Pennathur S, Joe B. Evidence for a link between gut microbiota and hypertension in the Dahl rat. Physiol Genomics. 2015;47:187–97. doi:10.1152/physiolgenomics.00136.2014.CrossRefPubMedPubMedCentral Mell B, Jala VR, Mathew AV, Byun J, Waghulde H, Zhang Y, Haribabu B, Vijay-Kumar M, Pennathur S, Joe B. Evidence for a link between gut microbiota and hypertension in the Dahl rat. Physiol Genomics. 2015;47:187–97. doi:10.​1152/​physiolgenomics.​00136.​2014.CrossRefPubMedPubMedCentral

go back to reference • Yang T, Santisteban MM, Rodriguez V, Li E, Ahmari N, Carvajal JM, Zadeh M, Gong M, Qi Y, Zubcevic J, Sahay B, Pepine CJ, Raizada MK, Mohamadzadeh M. Gut dysbiosis is linked to hypertension. Hypertension. 2015;65:1331–40. doi:10.1161/HYPERTENSIONAHA.115.05315. This article demonstrated gut dysbiosis in both rats and hypertensive patients. Dysbiosis was characterized by an increased F:B ratio and loss of SCFA-producing bacteria. CrossRefPubMedPubMedCentral • Yang T, Santisteban MM, Rodriguez V, Li E, Ahmari N, Carvajal JM, Zadeh M, Gong M, Qi Y, Zubcevic J, Sahay B, Pepine CJ, Raizada MK, Mohamadzadeh M. Gut dysbiosis is linked to hypertension. Hypertension. 2015;65:1331–40. doi:10.​1161/​HYPERTENSIONAHA.​115.​05315. This article demonstrated gut dysbiosis in both rats and hypertensive patients. Dysbiosis was characterized by an increased F:B ratio and loss of SCFA-producing bacteria. CrossRefPubMedPubMedCentral

go back to reference Santisteban MM, Kim S, Pepine CJ, Raizada MK. Brain-gut-bone marrow axis: implications for hypertension and related therapeutics. Circ Res. 2016;118:1327–36. doi:10.1161/CIRCRESAHA.116.307709.CrossRefPubMedPubMedCentral Santisteban MM, Kim S, Pepine CJ, Raizada MK. Brain-gut-bone marrow axis: implications for hypertension and related therapeutics. Circ Res. 2016;118:1327–36. doi:10.​1161/​CIRCRESAHA.​116.​307709.CrossRefPubMedPubMedCentral

go back to reference •• Santisteban MM, Qi Y, Zubcevic J, Kim S, Yang T, Shenoy V, Cole-Jeffrey CT, Lobaton GO, Stewart DC, Rubiano A, Simmons CS, Garcia-Pereira F, Johnson RD, Pepine CJ, Raizada MK. Hypertension-linked pathophysiological alterations in the gut. Circ Res. 2017;120:312–23. doi:10.1161/CIRCRESAHA.116.309006. This article demonstrated dysbiosis as well as gut pathology in SHR and AngII rat models of hypertension. Studies suggest dysfunctional sympathetic-gut communication is involved in gut pathology, dysbiosis, inflammation, and hypertension. CrossRefPubMed •• Santisteban MM, Qi Y, Zubcevic J, Kim S, Yang T, Shenoy V, Cole-Jeffrey CT, Lobaton GO, Stewart DC, Rubiano A, Simmons CS, Garcia-Pereira F, Johnson RD, Pepine CJ, Raizada MK. Hypertension-linked pathophysiological alterations in the gut. Circ Res. 2017;120:312–23. doi:10.​1161/​CIRCRESAHA.​116.​309006. This article demonstrated dysbiosis as well as gut pathology in SHR and AngII rat models of hypertension. Studies suggest dysfunctional sympathetic-gut communication is involved in gut pathology, dysbiosis, inflammation, and hypertension. CrossRefPubMed

go back to reference • 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. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome. 2017;5:14. doi:10.1186/s40168-016-0222-x. This study demonstrated significant differences in the gut microbiota, microbiota metagenome, and plasma metabolites of prehypertensive and hypertensive patients, as compared to controls. CrossRefPubMedPubMedCentral • 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. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome. 2017;5:14. doi:10.​1186/​s40168-016-0222-x. This study demonstrated significant differences in the gut microbiota, microbiota metagenome, and plasma metabolites of prehypertensive and hypertensive patients, as compared to controls. CrossRefPubMedPubMedCentral

go back to reference Hooper LV, Gordon JI. Commensal host-bacterial relationships in the gut. Science. 2001;292:1115–8.CrossRefPubMed Hooper LV, Gordon JI. Commensal host-bacterial relationships in the gut. Science. 2001;292:1115–8.CrossRefPubMed

go back to reference Lee YK, Mazmanian SK. Has the microbiota played a critical role in the evolution of the adaptive immune system? Science. 2010;330:1768–73. doi:10.1126/science.1195568.CrossRefPubMedPubMedCentral Lee YK, Mazmanian SK. Has the microbiota played a critical role in the evolution of the adaptive immune system? Science. 2010;330:1768–73. doi:10.​1126/​science.​1195568.CrossRefPubMedPubMedCentral

go back to reference Schippa S, Conte MP. Dysbiotic events in gut microbiota: impact on human health. Nutrients. 2014;6:5786–805.CrossRefPubMedPubMedCentral Schippa S, Conte MP. Dysbiotic events in gut microbiota: impact on human health. Nutrients. 2014;6:5786–805.CrossRefPubMedPubMedCentral

go back to reference Tang WH, Hazen SL. The contributory role of gut microbiota in cardiovascular disease. J Clin Invest. 2014;124:4204–11. doi:10.1172/JCI72331.CrossRefPubMedPubMedCentral Tang WH, Hazen SL. The contributory role of gut microbiota in cardiovascular disease. J Clin Invest. 2014;124:4204–11. doi:10.​1172/​JCI72331.CrossRefPubMedPubMedCentral

go back to reference Gregory JC, Buffa JA, Org E, Wang Z, Levison BS, Zhu W, Wagner MA, Bennett BJ, Li L, DiDonato JA, Lusis AJ, Hazen SL. Transmission of atherosclerosis susceptibility with gut microbial transplantation. J Biol Chem. 2015;290:5647–60. doi:10.1074/jbc.M114.618249.CrossRefPubMed Gregory JC, Buffa JA, Org E, Wang Z, Levison BS, Zhu W, Wagner MA, Bennett BJ, Li L, DiDonato JA, Lusis AJ, Hazen SL. Transmission of atherosclerosis susceptibility with gut microbial transplantation. J Biol Chem. 2015;290:5647–60. doi:10.​1074/​jbc.​M114.​618249.CrossRefPubMed

go back to reference Koeth RA, Levison BS, Culley MK, Buffa JA, Wang Z, Gregory JC, Org E, Wu Y, Li L, Smith JD, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gamma-butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of L-carnitine to TMAO. Cell Metab. 2014;20:799–812. doi:10.1016/j.cmet.2014.10.006.CrossRefPubMedPubMedCentral Koeth RA, Levison BS, Culley MK, Buffa JA, Wang Z, Gregory JC, Org E, Wu Y, Li L, Smith JD, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gamma-butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of L-carnitine to TMAO. Cell Metab. 2014;20:799–812. doi:10.​1016/​j.​cmet.​2014.​10.​006.CrossRefPubMedPubMedCentral

go back to reference Everard A, Cani PD. Diabetes, obesity and gut microbiota. Best Pract Res Clin Gastroenterol. 2013;27:73–83. doi:10.1016/j.bpg.2013.03.007.CrossRefPubMed Everard A, Cani PD. Diabetes, obesity and gut microbiota. Best Pract Res Clin Gastroenterol. 2013;27:73–83. doi:10.​1016/​j.​bpg.​2013.​03.​007.CrossRefPubMed

go back to reference Benakis C, Brea D, Caballero S, Faraco G, Moore J, Murphy M, Sita G, Racchumi G, Ling L, Pamer EG, Iadecola C, Anrather J. Commensal microbiota affects ischemic stroke outcome by regulating intestinal gammadelta T cells. Nat Med. 2016;22:516–23. doi:10.1038/nm.4068.CrossRefPubMedPubMedCentral Benakis C, Brea D, Caballero S, Faraco G, Moore J, Murphy M, Sita G, Racchumi G, Ling L, Pamer EG, Iadecola C, Anrather J. Commensal microbiota affects ischemic stroke outcome by regulating intestinal gammadelta T cells. Nat Med. 2016;22:516–23. doi:10.​1038/​nm.​4068.CrossRefPubMedPubMedCentral

go back to reference Singh V, Roth S, Llovera G, Sadler R, Garzetti D, Stecher B, Dichgans M, Liesz A. Microbiota dysbiosis controls the neuroinflammatory response after stroke. J Neurosci. 2016;36:7428–40. doi:10.1523/JNEUROSCI.1114-16.2016.CrossRefPubMed Singh V, Roth S, Llovera G, Sadler R, Garzetti D, Stecher B, Dichgans M, Liesz A. Microbiota dysbiosis controls the neuroinflammatory response after stroke. J Neurosci. 2016;36:7428–40. doi:10.​1523/​JNEUROSCI.​1114-16.​2016.CrossRefPubMed

go back to reference Cattaneo A, Cattane N, Galluzzi S, Provasi S, Lopizzo N, Festari C, Ferrari C, Guerra UP, Paghera B, Muscio C, Bianchetti A, Volta GD, Turla M, Cotelli MS, Gennuso M, Prelle A, Zanetti O, Lussignoli G, Mirabile D, Bellandi D, Gentile S, Belotti G, Villani D, Harach T, Bolmont T, Padovani A, Boccardi M, Frisoni GB, INDIA-FBP group. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging. 2017;49:60–8.CrossRefPubMed Cattaneo A, Cattane N, Galluzzi S, Provasi S, Lopizzo N, Festari C, Ferrari C, Guerra UP, Paghera B, Muscio C, Bianchetti A, Volta GD, Turla M, Cotelli MS, Gennuso M, Prelle A, Zanetti O, Lussignoli G, Mirabile D, Bellandi D, Gentile S, Belotti G, Villani D, Harach T, Bolmont T, Padovani A, Boccardi M, Frisoni GB, INDIA-FBP group. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging. 2017;49:60–8.CrossRefPubMed

go back to reference Brown JM, Hazen SL. Metaorganismal nutrient metabolism as a basis of cardiovascular disease. Curr Opin Lipidol. 2014;25:48–53. doi:10.1097/MOL.0000000000000036.CrossRefPubMedPubMedCentral Brown JM, Hazen SL. Metaorganismal nutrient metabolism as a basis of cardiovascular disease. Curr Opin Lipidol. 2014;25:48–53. doi:10.​1097/​MOL.​0000000000000036​.CrossRefPubMedPubMedCentral

go back to reference Canani RB, Costanzo MD, Leone L, Pedata M, Meli R, Calignano A. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol. 2011;17:1519–28. doi:10.3748/wjg.v17.i12.1519.CrossRefPubMedPubMedCentral Canani RB, Costanzo MD, Leone L, Pedata M, Meli R, Calignano A. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol. 2011;17:1519–28. doi:10.​3748/​wjg.​v17.​i12.​1519.CrossRefPubMedPubMedCentral

go back to reference Berni Canani R, Di Costanzo M, Leone L. The epigenetic effects of butyrate: potential therapeutic implications for clinical practice. Clin Epigenetics. 2012;4:4. doi:10.1186/1868-7083-4-4.CrossRefPubMedPubMedCentral Berni Canani R, Di Costanzo M, Leone L. The epigenetic effects of butyrate: potential therapeutic implications for clinical practice. Clin Epigenetics. 2012;4:4. doi:10.​1186/​1868-7083-4-4.CrossRefPubMedPubMedCentral

go back to reference Vinolo MA, Rodrigues HG, Nachbar RT, Curi R. Regulation of inflammation by short chain fatty acids. Nutrients. 2011;3:858–76. doi:10.3390/nu3100858.CrossRefPubMedPubMedCentral Vinolo MA, Rodrigues HG, Nachbar RT, Curi R. Regulation of inflammation by short chain fatty acids. Nutrients. 2011;3:858–76. doi:10.​3390/​nu3100858.CrossRefPubMedPubMedCentral

go back to reference Fung KY, Cosgrove L, Lockett T, Head R, Topping DL. A review of the potential mechanisms for the lowering of colorectal oncogenesis by butyrate. Br J Nutr. 2012;108:820–31. doi:10.1017/S0007114512001948.CrossRefPubMed Fung KY, Cosgrove L, Lockett T, Head R, Topping DL. A review of the potential mechanisms for the lowering of colorectal oncogenesis by butyrate. Br J Nutr. 2012;108:820–31. doi:10.​1017/​S000711451200194​8.CrossRefPubMed

go back to reference • Adnan S, Nelson JW, Ajami NJ, Venna VR, Petrosino JF, Bryan Jr RM, Durgan DJ. Alterations in the gut microbiota can elicit hypertension in rats. Physiol Genomics. 2016; doi:10.1152/physiolgenomics.00081.2016. This article demonstrated dysbiosis in the SHRSP model. In addition, the hypertensive phenotype could be transferred to normotensive rats by microbiota transplantation. PubMed • Adnan S, Nelson JW, Ajami NJ, Venna VR, Petrosino JF, Bryan Jr RM, Durgan DJ. Alterations in the gut microbiota can elicit hypertension in rats. Physiol Genomics. 2016; doi:10.​1152/​physiolgenomics.​00081.​2016. This article demonstrated dysbiosis in the SHRSP model. In addition, the hypertensive phenotype could be transferred to normotensive rats by microbiota transplantation. PubMed

go back to reference Karbach SH, Schonfelder T, Brandao I, Wilms E, Hormann N, Jackel S, Schuler R, Finger S, Knorr M, Lagrange J, Brandt M, Waisman A, Kossmann S, Schafer K, Munzel T, Reinhardt C, Wenzel P. Gut microbiota promote angiotensin II-induced arterial hypertension and vascular dysfunction. J Am Heart Assoc. 2016;5 doi:10.1161/JAHA.116.003698. Karbach SH, Schonfelder T, Brandao I, Wilms E, Hormann N, Jackel S, Schuler R, Finger S, Knorr M, Lagrange J, Brandt M, Waisman A, Kossmann S, Schafer K, Munzel T, Reinhardt C, Wenzel P. Gut microbiota promote angiotensin II-induced arterial hypertension and vascular dysfunction. J Am Heart Assoc. 2016;5 doi:10.​1161/​JAHA.​116.​003698.

go back to reference Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, Rostron T, Cerundolo V, Pamer EG, Abramson SB, Huttenhower C, Littman DR. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. elife. 2013;2:e01202. doi:10.7554/eLife.01202.CrossRefPubMedPubMedCentral Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, Rostron T, Cerundolo V, Pamer EG, Abramson SB, Huttenhower C, Littman DR. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. elife. 2013;2:e01202. doi:10.​7554/​eLife.​01202.CrossRefPubMedPubMedCentral

go back to reference Kohn FR, Kung AH. Role of endotoxin in acute inflammation induced by gram-negative bacteria: specific inhibition of lipopolysaccharide-mediated responses with an amino-terminal fragment of bactericidal/permeability-increasing protein. Infect Immun. 1995;63:333–9.PubMedPubMedCentral Kohn FR, Kung AH. Role of endotoxin in acute inflammation induced by gram-negative bacteria: specific inhibition of lipopolysaccharide-mediated responses with an amino-terminal fragment of bactericidal/permeability-increasing protein. Infect Immun. 1995;63:333–9.PubMedPubMedCentral

go back to reference Moreno-Indias I, Torres M, Montserrat JM, Sanchez-Alcoholado L, Cardona F, Tinahones FJ, Gozal D, Poroyko VA, Navajas D, Queipo-Ortuno MI, Farre R. Intermittent hypoxia alters gut microbiota diversity in a mouse model of sleep apnoea. Eur Respir J. 2015;45:1055–65. doi:10.1183/09031936.00184314.CrossRefPubMed Moreno-Indias I, Torres M, Montserrat JM, Sanchez-Alcoholado L, Cardona F, Tinahones FJ, Gozal D, Poroyko VA, Navajas D, Queipo-Ortuno MI, Farre R. Intermittent hypoxia alters gut microbiota diversity in a mouse model of sleep apnoea. Eur Respir J. 2015;45:1055–65. doi:10.​1183/​09031936.​00184314.CrossRefPubMed

go back to reference Moreno-Indias I, Torres M, Sanchez-Alcoholado L, Cardona F, Almendros I, Gozal D, Montserrat JM, Queipo-Ortuno MI, Farre R. Normoxic recovery mimicking treatment of sleep apnea does not reverse intermittent hypoxia-induced bacterial dysbiosis and low-grade endotoxemia in mice. Sleep. 2016;39:1891–7. doi:10.5665/sleep.6176.CrossRefPubMedPubMedCentral Moreno-Indias I, Torres M, Sanchez-Alcoholado L, Cardona F, Almendros I, Gozal D, Montserrat JM, Queipo-Ortuno MI, Farre R. Normoxic recovery mimicking treatment of sleep apnea does not reverse intermittent hypoxia-induced bacterial dysbiosis and low-grade endotoxemia in mice. Sleep. 2016;39:1891–7. doi:10.​5665/​sleep.​6176.CrossRefPubMedPubMedCentral

go back to reference Wu J, Sun X, Wu Q, Li H, Li L, Feng J, Zhang S, Xu L, Li K, Li X, Wang X, Chen H. Disrupted intestinal structure in a rat model of intermittent hypoxia. Mol Med Rep. 2016;13:4407–13. doi:10.3892/mmr.2016.5068.PubMed Wu J, Sun X, Wu Q, Li H, Li L, Feng J, Zhang S, Xu L, Li K, Li X, Wang X, Chen H. Disrupted intestinal structure in a rat model of intermittent hypoxia. Mol Med Rep. 2016;13:4407–13. doi:10.​3892/​mmr.​2016.​5068.PubMed

go back to reference Poroyko VA, Carreras A, Khalyfa A, Khalyfa AA, Leone V, Peris E, Almendros I, Gileles-Hillel A, Qiao Z, Hubert N, Farre R, Chang EB, Gozal D. Chronic sleep disruption alters gut microbiota, induces systemic and adipose tissue inflammation and insulin resistance in mice. Sci Rep. 2016;6:35405. doi:10.1038/srep35405.CrossRefPubMedPubMedCentral Poroyko VA, Carreras A, Khalyfa A, Khalyfa AA, Leone V, Peris E, Almendros I, Gileles-Hillel A, Qiao Z, Hubert N, Farre R, Chang EB, Gozal D. Chronic sleep disruption alters gut microbiota, induces systemic and adipose tissue inflammation and insulin resistance in mice. Sci Rep. 2016;6:35405. doi:10.​1038/​srep35405.CrossRefPubMedPubMedCentral

go back to reference Mittal R, Debs LH, Patel AP, Nguyen D, Patel K, O'Connor G, Grati M, Mittal J, Yan D, Eshraghi AA, Deo SK, Daunert S, Liu XZ. Neurotransmitters: the critical modulators regulating gut-brain axis. J Cell Physiol. 2016; doi:10.1002/jcp.25518. Mittal R, Debs LH, Patel AP, Nguyen D, Patel K, O'Connor G, Grati M, Mittal J, Yan D, Eshraghi AA, Deo SK, Daunert S, Liu XZ. Neurotransmitters: the critical modulators regulating gut-brain axis. J Cell Physiol. 2016; doi:10.​1002/​jcp.​25518.

go back to reference Lyte M, Vulchanova L, Brown DR. Stress at the intestinal surface: catecholamines and mucosa-bacteria interactions. Cell Tissue Res. 2011;343:23–32. doi:10.1007/s00441-010-1050-0.CrossRefPubMed Lyte M, Vulchanova L, Brown DR. Stress at the intestinal surface: catecholamines and mucosa-bacteria interactions. Cell Tissue Res. 2011;343:23–32. doi:10.​1007/​s00441-010-1050-0.CrossRefPubMed

go back to reference Bhatia V, Tandon RK. Stress and the gastrointestinal tract. J Gastroenterol Hepatol. 2005;20:332–9.CrossRefPubMed Bhatia V, Tandon RK. Stress and the gastrointestinal tract. J Gastroenterol Hepatol. 2005;20:332–9.CrossRefPubMed

go back to reference Lyte M. Microbial endocrinology: host-microbiota neuroendocrine interactions influencing brain and behavior. Gut Microbes. 2014;5:381–9. doi:10.4161/gmic.28682.CrossRefPubMedPubMedCentral Lyte M. Microbial endocrinology: host-microbiota neuroendocrine interactions influencing brain and behavior. Gut Microbes. 2014;5:381–9. doi:10.​4161/​gmic.​28682.CrossRefPubMedPubMedCentral

go back to reference Mackos AR, Varaljay VA, Maltz R, Gur TL, Bailey MT. Role of the intestinal microbiota in host responses to stressor exposure. Int Rev Neurobiol. 2016;131:1–19.CrossRefPubMed Mackos AR, Varaljay VA, Maltz R, Gur TL, Bailey MT. Role of the intestinal microbiota in host responses to stressor exposure. Int Rev Neurobiol. 2016;131:1–19.CrossRefPubMed

go back to reference Pluznick JL, Zou DJ, Zhang X, Yan Q, Rodriguez-Gil DJ, Eisner C, Wells E, Greer CA, Wang T, Firestein S, Schnermann J, Caplan MJ. Functional expression of the olfactory signaling system in the kidney. Proc Natl Acad Sci U S A. 2009;106:2059–64. doi:10.1073/pnas.0812859106.CrossRefPubMedPubMedCentral Pluznick JL, Zou DJ, Zhang X, Yan Q, Rodriguez-Gil DJ, Eisner C, Wells E, Greer CA, Wang T, Firestein S, Schnermann J, Caplan MJ. Functional expression of the olfactory signaling system in the kidney. Proc Natl Acad Sci U S A. 2009;106:2059–64. doi:10.​1073/​pnas.​0812859106.CrossRefPubMedPubMedCentral

go back to reference Rajkumar P, Aisenberg WH, Acres OW, Protzko RJ, Pluznick JL. Identification and characterization of novel renal sensory receptors. PLoS One. 2014;9:e111053. doi:10.1371/journal.pone.0111053.CrossRefPubMedPubMedCentral Rajkumar P, Aisenberg WH, Acres OW, Protzko RJ, Pluznick JL. Identification and characterization of novel renal sensory receptors. PLoS One. 2014;9:e111053. doi:10.​1371/​journal.​pone.​0111053.CrossRefPubMedPubMedCentral

go back to reference Natarajan N, Hori D, Flavahan S, Steppan J, Flavahan NA, Berkowitz DE, Pluznick JL. Microbial short chain fatty acid metabolites lower blood pressure via endothelial G-protein coupled receptor 41. Physiol Genomics. 2016; doi:10.1152/physiolgenomics.00089.2016.PubMedCentral Natarajan N, Hori D, Flavahan S, Steppan J, Flavahan NA, Berkowitz DE, Pluznick JL. Microbial short chain fatty acid metabolites lower blood pressure via endothelial G-protein coupled receptor 41. Physiol Genomics. 2016; doi:10.​1152/​physiolgenomics.​00089.​2016.PubMedCentral

go back to reference Pluznick JL, Protzko RJ, Gevorgyan H, Peterlin Z, Sipos A, Han J, Brunet I, Wan LX, Rey F, Wang T, Firestein SJ, Yanagisawa M, Gordon JI, Eichmann A, Peti-Peterdi J, Caplan MJ. 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. doi:10.1073/pnas.1215927110.CrossRefPubMedPubMedCentral Pluznick JL, Protzko RJ, Gevorgyan H, Peterlin Z, Sipos A, Han J, Brunet I, Wan LX, Rey F, Wang T, Firestein SJ, Yanagisawa M, Gordon JI, Eichmann A, Peti-Peterdi J, Caplan MJ. 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. doi:10.​1073/​pnas.​1215927110.CrossRefPubMedPubMedCentral

go back to reference Schiffrin EL. The immune system: role in hypertension. Can J Cardiol. 2013;29:543–8. doi:10.1016/j.cjca.2012.06.009.CrossRefPubMed Schiffrin EL. The immune system: role in hypertension. Can J Cardiol. 2013;29:543–8. doi:10.​1016/​j.​cjca.​2012.​06.​009.CrossRefPubMed

go back to reference Singh MV, Chapleau MW, Harwani SC, Abboud FM. The immune system and hypertension. Immunol Res. 2014;59:243–53. doi:10.1007/s12026-014-8548-6.CrossRefPubMedPubMedCentral Singh MV, Chapleau MW, Harwani SC, Abboud FM. The immune system and hypertension. Immunol Res. 2014;59:243–53. doi:10.​1007/​s12026-014-8548-6.CrossRefPubMedPubMedCentral

go back to reference Singh MV, Abboud FM. Toll-like receptors and hypertension. Am J Physiol Regul Integr Comp Physiol. 2014;307:R501–4. doi:10.1152/ajpregu.00194.2014.CrossRefPubMedPubMedCentral Singh MV, Abboud FM. Toll-like receptors and hypertension. Am J Physiol Regul Integr Comp Physiol. 2014;307:R501–4. doi:10.​1152/​ajpregu.​00194.​2014.CrossRefPubMedPubMedCentral

go back to reference Harrison DG, Guzik TJ, Lob HE, Madhur MS, Marvar PJ, Thabet SR, Vinh A, Weyand CM. Inflammation, immunity, and hypertension. Hypertension. 2011;57:132–40. doi:10.1161/HYPERTENSIONAHA.110.163576.CrossRefPubMed Harrison DG, Guzik TJ, Lob HE, Madhur MS, Marvar PJ, Thabet SR, Vinh A, Weyand CM. Inflammation, immunity, and hypertension. Hypertension. 2011;57:132–40. doi:10.​1161/​HYPERTENSIONAHA.​110.​163576.CrossRefPubMed

go back to reference Nobili V, Alisi A, Cutrera R, Carpino G, De Stefanis C, D'Oria V, De Vito R, Cucchiara S, Gaudio E, Musso G. Altered gut-liver axis and hepatic adiponectin expression in OSAS: novel mediators of liver injury in paediatric non-alcoholic fatty liver. Thorax. 2015;70:769–81. doi:10.1136/thoraxjnl-2015-206782.CrossRefPubMed Nobili V, Alisi A, Cutrera R, Carpino G, De Stefanis C, D'Oria V, De Vito R, Cucchiara S, Gaudio E, Musso G. Altered gut-liver axis and hepatic adiponectin expression in OSAS: novel mediators of liver injury in paediatric non-alcoholic fatty liver. Thorax. 2015;70:769–81. doi:10.​1136/​thoraxjnl-2015-206782.CrossRefPubMed

go back to reference Aron-Wisnewsky J, Clement K, Pepin JL. Nonalcoholic fatty liver disease and obstructive sleep apnea. Metabolism. 2016;65:1124–35. doi:10.1016/j.metabol.2016.05.004.CrossRefPubMed Aron-Wisnewsky J, Clement K, Pepin JL. Nonalcoholic fatty liver disease and obstructive sleep apnea. Metabolism. 2016;65:1124–35. doi:10.​1016/​j.​metabol.​2016.​05.​004.CrossRefPubMed

go back to reference Kheirandish-Gozal L, Peris E, Wang Y, Tamae Kakazu M, Khalyfa A, Carreras A, Gozal D. Lipopolysaccharide-binding protein plasma levels in children: effects of obstructive sleep apnea and obesity. J Clin Endocrinol Metab. 2014;99:656–63. doi:10.1210/jc.2013-3327.CrossRefPubMed Kheirandish-Gozal L, Peris E, Wang Y, Tamae Kakazu M, Khalyfa A, Carreras A, Gozal D. Lipopolysaccharide-binding protein plasma levels in children: effects of obstructive sleep apnea and obesity. J Clin Endocrinol Metab. 2014;99:656–63. doi:10.​1210/​jc.​2013-3327.CrossRefPubMed

go back to reference Barcelo A, Esquinas C, Robles J, Pierola J, De la Pena M, Aguilar I, Morell-Garcia D, Alonso A, Toledo N, Sanchez-de la Torre M, Barbe F. Gut epithelial barrier markers in patients with obstructive sleep apnea. Sleep Med. 2016;26:12–5.CrossRefPubMed Barcelo A, Esquinas C, Robles J, Pierola J, De la Pena M, Aguilar I, Morell-Garcia D, Alonso A, Toledo N, Sanchez-de la Torre M, Barbe F. Gut epithelial barrier markers in patients with obstructive sleep apnea. Sleep Med. 2016;26:12–5.CrossRefPubMed

go back to reference Morris G, Berk M, Carvalho A, Caso JR, Sanz Y, Walder K, Maes M. The role of the microbial metabolites including tryptophan catabolites and short chain fatty acids in the pathophysiology of immune-inflammatory and neuroimmune disease. Mol Neurobiol. 2016; doi:10.1007/s12035-016-0004-2. Morris G, Berk M, Carvalho A, Caso JR, Sanz Y, Walder K, Maes M. The role of the microbial metabolites including tryptophan catabolites and short chain fatty acids in the pathophysiology of immune-inflammatory and neuroimmune disease. Mol Neurobiol. 2016; doi:10.​1007/​s12035-016-0004-2.

go back to reference Zhang M, Zhou Q, Dorfman RG, Huang X, Fan T, Zhang H, Zhang J, Yu C. Butyrate inhibits interleukin-17 and generates Tregs to ameliorate colorectal colitis in rats. BMC Gastroenterol. 2016;16 doi:10.1186/s12876-016-0500-x. Zhang M, Zhou Q, Dorfman RG, Huang X, Fan T, Zhang H, Zhang J, Yu C. Butyrate inhibits interleukin-17 and generates Tregs to ameliorate colorectal colitis in rats. BMC Gastroenterol. 2016;16 doi:10.​1186/​s12876-016-0500-x.

go back to reference Nakamura Y, Masuda O, Takano T. Decrease of tissue angiotensin I-converting enzyme activity upon feeding sour milk in spontaneously hypertensive rats. Biosci Biotechnol Biochem. 1996;60:488–9.CrossRefPubMed Nakamura Y, Masuda O, Takano T. Decrease of tissue angiotensin I-converting enzyme activity upon feeding sour milk in spontaneously hypertensive rats. Biosci Biotechnol Biochem. 1996;60:488–9.CrossRefPubMed

go back to reference Fuglsang A, Rattray FP, Nilsson D, Nyborg NC. Lactic acid bacteria: inhibition of angiotensin converting enzyme in vitro and in vivo. Antonie Van Leeuwenhoek. 2003;83:27–34.CrossRefPubMed Fuglsang A, Rattray FP, Nilsson D, Nyborg NC. Lactic acid bacteria: inhibition of angiotensin converting enzyme in vitro and in vivo. Antonie Van Leeuwenhoek. 2003;83:27–34.CrossRefPubMed

go back to reference Liu CF, Tung YT, Wu CL, Lee BH, Hsu WH, Pan TM. Antihypertensive effects of Lactobacillus-fermented milk orally administered to spontaneously hypertensive rats. J Agric Food Chem. 2011;59:4537–43. doi:10.1021/jf104985v.CrossRefPubMed Liu CF, Tung YT, Wu CL, Lee BH, Hsu WH, Pan TM. Antihypertensive effects of Lactobacillus-fermented milk orally administered to spontaneously hypertensive rats. J Agric Food Chem. 2011;59:4537–43. doi:10.​1021/​jf104985v.CrossRefPubMed

go back to reference Gomez-Guzman M, Toral M, Romero M, Jimenez R, Galindo P, Sanchez M, Zarzuelo MJ, Olivares M, Galvez J, Duarte J. Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats. Mol Nutr Food Res. 2015;59:2326–36. doi:10.1002/mnfr.201500290.CrossRefPubMed Gomez-Guzman M, Toral M, Romero M, Jimenez R, Galindo P, Sanchez M, Zarzuelo MJ, Olivares M, Galvez J, Duarte J. Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats. Mol Nutr Food Res. 2015;59:2326–36. doi:10.​1002/​mnfr.​201500290.CrossRefPubMed

go back to reference 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. doi:10.1161/HYPERTENSIONAHA.114.03469.CrossRefPubMed 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. doi:10.​1161/​HYPERTENSIONAHA.​114.​03469.CrossRefPubMed

go back to reference Hata Y, Yamamoto M, Ohni M, Nakajima K, Nakamura Y, Takano T. A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects. Am J Clin Nutr. 1996;64:767–71.PubMed Hata Y, Yamamoto M, Ohni M, Nakajima K, Nakamura Y, Takano T. A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects. Am J Clin Nutr. 1996;64:767–71.PubMed

go back to reference Pamer EG. Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens. Science. 2016;352:535–8. doi:10.1126/science.aad9382.CrossRefPubMedPubMedCentral Pamer EG. Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens. Science. 2016;352:535–8. doi:10.​1126/​science.​aad9382.CrossRefPubMedPubMedCentral