rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2018-14-4-567-574rpcardio-1727Research ArticleINNOVATIVE CARDIOLOGYИННОВАЦИОННАЯ КАРДИОЛОГИЯRole of Gut Microbiota in the Pathogenesis of Cardiovascular Diseases and Metabolic SyndromeРоль кишечной микробиоты в патогенезе сердечно-сосудистых заболеваний и метаболического синдромаДрапкинаО. М.DrapkinaO. M.

Драпкина Оксана Михайловна – доктор медицинских наук, профессор, член-корреспондент РАН, директор

101990, Москва, Петроверигский переулок, 10 стр. 3

ШиробокихО. Е.ShirobokikhO. E.

Широбоких Ольга Евгеньевна – клинический ординатор

101990, Москва, Петроверигский переулок, 10 стр. 3

olgashirobokikh@gmail.comНациональный медицинский исследовательский центр профилактической медициныРоссияNational Medical Research Center for Preventive MedicineRussian Federation201804092018144567574Copyright © Drapkina O.M., Shirobokikh O.E., 20182018Драпкина О.М., Широбоких О.Е.Drapkina O.M., Shirobokikh O.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpcardio.online/jour/article/view/1727

The role of gut microbiota in the pathogenesis of cardiovascular diseases (CVD) and metabolic syndrome has attracted massive attention in the past decade. Accumulating evidence has revealed that the metabolic potential of gut microbiota can be identified as a contributing factor in the development of atherosclerosis, hypertension, heart failure, obesity, diabetes mellitus. The gut-host interaction occurs through many pathways including trimethylamine-N-oxide pathway (TMAO), short-chain fatty acids and second bile acids pathways. TMAO (the hepatic oxidation product of the microbial metabolite of trimethylamine) enhances platelet hyperreactivity and thrombosis risk and predicts major adverse cardiovascular events. Short-chain fatty acids and second bile acids, which are produced with the help of microbiota, can modulate host lipid metabolism as well as carbohydrate metabolism through several receptors such as G-protein-coupled receptors 41,43, farnesoid X-receptor, Takeda-G-protein-receptor-5. This way microbiota can impact host lipid levels, processes of weight gain, insulin sensitivity. Besides these metabolism-dependent pathways, there are some other pathways, which link microbiota and the pathogenesis of CVD. For example, lipopolysaccharide, the major component of the outer bacterial membrane, causes metabolic endotoxemia and low-grade systemic inflammation and contribute this way to obesity and progression of heart failure and atherosclerosis. This review aims to illustrate the complex interplay between microbiota, their metabolites, and the development and progression of CVD and metabolic syndrome. It is also discussed how modulating of gut microbiota composition and function through diet, prebiotics, probiotics and fecal microbiota transplantation can become a novel therapeutic and preventative target for CVD and metabolic syndrome. Many questions remain unresolved in this field and undoubtedly further studies are needed.

Последние годы внимание ученых привлекает роль кишечной микробиоты в патогенезе сердечно-сосудистых заболеваний (ССЗ) и метаболического синдрома. Накоплены данные, подтверждающие, что метаболиты бактерий кишечника вносят вклад в развитие атеросклероза, артериальной гипертонии, сердечной недостаточности, ожирения и сахарного диабета. Взаимодействие микробиоты и организма человека-хозяина осуществляется посредством различных механизмов, в том числе, через обмен триметиламин-N-оксида (ТМАО), короткоцепочечных жирных кислот (КЦЖК) и вторичных желчных кислот (ЖК). ТМАО (продукт окисления в печени бактериального метаболита триметиламина) увеличивает гиперреактивность тромбоцитов, риск тромбозов и является предиктором развития крупных неблагоприятных сердечно-сосудистых событий. КЦЖК и вторичные ЖК, продуцирующиеся с участием микробиоты, способны влиять на жировой и углеводный обмены человека через такие рецепторы, как G-белок ассоциированные рецепторы 41,43, фарнезоидный Х рецептор печени, Takeda-Gбелок ассоциированный рецептор 5. Таким образом микробиота может влиять на уровни липидов, набор веса, чувствительность к инсулину. Помимо этих метаболизм-зависимых путей, связывающих микробиоту и патогенез ССЗ, существует несколько иных механизмов. Например, липополисахарид, компонент клеточной стенки бактерий, является причиной эндотоксемии и системного воспаления низкой интенсивности, внося вклад в развитие ожирения и прогрессирование атеросклероза и сердечной недостаточности. Целью данного обзора является освещение роли микробиоты и метаболитов бактерий в развитии и прогрессировании ССЗ и метаболического синдрома. Также обсуждено, как изменения состава кишечной микробиоты и ее функциональной активности посредством диеты, пребиотиков, пробиотиков и трансплантации фекальной микробиоты могут стать объектом профилактики и терапии ССЗ. Безусловно, в этой области остается много нерешенных вопросов, и необходимы дальнейшие исследования.

кишечная микробиотаожирениетриметиламин-N-оксидатеросклерозфарнезоидный Х рецепторgut microbiotaobesitytrimethylamine-N-oxideatherosclerosisfarnesoid X-receptorReferencesGBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the global burden of disease study 2013. Lancet. 2015;385:117-71. doi: 10.1016/S01406736(14)61682-2.GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the global burden of disease study 2013. Lancet. 2015;385:117-71. doi: 10.1016/S01406736(14)61682-2.Arumugam M., Raes J., Pelletier E.et al. Enterotypes of the human gut microbiome. Nature 2011;473:174-80. doi:10.1038/nature09944Arumugam M., Raes J., Pelletier E.et al. Enterotypes of the human gut microbiome. Nature 2011;473:174-80. doi:10.1038/nature09944Moran-Ramos S., López-Contreras B.E., Canizales-Quinteros S. Gut Microbiota in Obesity and Metabolic Abnormalities: A Matter of Composition or Functionality? Archives of Medical Research. 2017;48(8):735-53. doi: 10.1016/j.arcmed.2017.11.003.Moran-Ramos S., López-Contreras B.E., Canizales-Quinteros S. Gut Microbiota in Obesity and Metabolic Abnormalities: A Matter of Composition or Functionality? Archives of Medical Research. 2017;48(8):735-53. doi: 10.1016/j.arcmed.2017.11.003.Metagenomics of the Human Intestinal Tract. [cited 2018 May 25]. Available from: http://www.metahit.eu/index.php?id=234.Metagenomics of the Human Intestinal Tract. [cited 2018 May 25]. Available from: http://www.metahit.eu/index.php?id=234.Jingyuan F., Bonder M., Carmen Cenit M. et al. The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids. Circulation Research. 2015;117:817-24. doi: 10.1161/CIRCRESAHA.115.306807.Jingyuan F., Bonder M., Carmen Cenit M. et al. The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids. Circulation Research. 2015;117:817-24. doi: 10.1161/CIRCRESAHA.115.306807.Bäckhed F., Ding H., Wang T. et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA. 2004;44:15718-23. doi: 10.1073/pnas.0407076101.Bäckhed F., Ding H., Wang T. et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA. 2004;44:15718-23. doi: 10.1073/pnas.0407076101.Ridaura V.K., Faith J.J., Rey F.E., Cheng J.Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341(6150):1241214. doi: 10.1126/science.1241214.Ridaura V.K., Faith J.J., Rey F.E., Cheng J.Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341(6150):1241214. doi: 10.1126/science.1241214.Pluznick J. Microbial Short-Chain Fatty Acids and Blood Pressure Regulation. Curr Hypertens Rep. 2017;19(4):25. doi: 10.1007/s11906-017-0722-5.Pluznick J. Microbial Short-Chain Fatty Acids and Blood Pressure Regulation. Curr Hypertens Rep. 2017;19(4):25. doi: 10.1007/s11906-017-0722-5.Khan M., Gerasimidis K., Edwards C. Role of Gut Microbiota in the Aetiology of Obesity: Proposed Mechanisms and Review of the Literature. Journal of Obesity. 2016;2016:7353642. doi: 10.1155/2016/7353642.Khan M., Gerasimidis K., Edwards C. Role of Gut Microbiota in the Aetiology of Obesity: Proposed Mechanisms and Review of the Literature. Journal of Obesity. 2016;2016:7353642. doi: 10.1155/2016/7353642.Tang W.H., Kitai T., Hazen S.L. Gut Microbiota in Cardiovascular Health and Disease. Circ Res. 2017;120(7):1183-96. doi: 10.1161/CIRCRESAHA.117.309715.Tang W.H., Kitai T., Hazen S.L. Gut Microbiota in Cardiovascular Health and Disease. Circ Res. 2017;120(7):1183-96. doi: 10.1161/CIRCRESAHA.117.309715.Kaska L., Sledzinski T., Chomiczewska A. Improved glucose metabolism following bariatric surgery is associated with increased circulating bile acid concentrations and remodeling of the gut microbiome. World J Gastroenterol. 2016;22(39):8698-8719. doi: 10.3748/wjg.v22.i39.8698.Kaska L., Sledzinski T., Chomiczewska A. Improved glucose metabolism following bariatric surgery is associated with increased circulating bile acid concentrations and remodeling of the gut microbiome. World J Gastroenterol. 2016;22(39):8698-8719. doi: 10.3748/wjg.v22.i39.8698.Lau K., Srivatsav V., Rizwan A. et al. Bridging the Gap between Gut Microbial Dysbiosis and Cardiovascular Diseases. Nutrients. 2017;9:859; doi:10.3390/nu9080859.Lau K., Srivatsav V., Rizwan A. et al. Bridging the Gap between Gut Microbial Dysbiosis and Cardiovascular Diseases. Nutrients. 2017;9:859; doi:10.3390/nu9080859.Chávez-Talavera O., Tailleux A., Lefebvre P. et al. Bile Acid Control of Metabolism and Inflammation in Obesity, Type 2 Diabetes, Dyslipidemia, and Nonalcoholic Fatty Liver Disease. Gastroenterology. 2017;152(7):1679-94.e3. doi: 10.1053/j.gastro.2017.01.055.Chávez-Talavera O., Tailleux A., Lefebvre P. et al. Bile Acid Control of Metabolism and Inflammation in Obesity, Type 2 Diabetes, Dyslipidemia, and Nonalcoholic Fatty Liver Disease. Gastroenterology. 2017;152(7):1679-94.e3. doi: 10.1053/j.gastro.2017.01.055.Qin J., Li Y., Cai Z. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490:55-60. doi: 10.1038/nature11450.Qin J., Li Y., Cai Z. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490:55-60. doi: 10.1038/nature11450.Forslund K., Hildebrand F., Nielsen et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528:262-6. doi: 10.1038/nature15766.Forslund K., Hildebrand F., Nielsen et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528:262-6. doi: 10.1038/nature15766.Karlsson F.H.,Tremaroli V., Nookaew I. et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature. 2013;498(7452):99-103. doi: 10.1038/nature12198.Karlsson F.H.,Tremaroli V., Nookaew I. et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature. 2013;498(7452):99-103. doi: 10.1038/nature12198.Vrieze A., Van Nood E., Holleman F. et al.Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143(4):9136.e7. doi: 10.1053/j.gastro.2012.06.031.Vrieze A., Van Nood E., Holleman F. et al.Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143(4):9136.e7. doi: 10.1053/j.gastro.2012.06.031.Samuel B.S., Shaito A., Motoike T. et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci USA. 2008;105:16767-72. doi: 10.1073/pnas.0808567105.Samuel B.S., Shaito A., Motoike T. et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci USA. 2008;105:16767-72. doi: 10.1073/pnas.0808567105.Koeth R.A., Wang Z., Levison B.S. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19(5):576-85. doi: 10.1038/nm.3145.Koeth R.A., Wang Z., Levison B.S. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19(5):576-85. doi: 10.1038/nm.3145.WangZ. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472:57-63.doi:10.1038/nature09922.WangZ. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472:57-63.doi: 10.1038/nature09922.Gregory J.C., Buffa J.A., Org E. et al. Transmission of atherosclerosis susceptibility with gut microbial transplantation. J Biol Chem. 2015;290:5647-60. doi: 10.1074/jbc.M114.618249.Gregory J.C., Buffa J.A., Org E. et al. Transmission of atherosclerosis susceptibility with gut microbial transplantation. J Biol Chem. 2015;290:5647-60. doi: 10.1074/jbc.M114.618249.Tang W.H., Wang Z., Levison B.S. et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368:1575-84. doi: 10.1056/NEJMoa1109400.Tang W.H., Wang Z., Levison B.S. et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368:1575-84. doi: 10.1056/NEJMoa1109400.Heianza Y., Ma W., Manson J.E.et al. Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta-Analysis of Prospective Studies. J Am Heart Assoc. 2017;6(7):e004947. doi: 10.1161/JAHA.116.004947.Heianza Y., Ma W., Manson J.E.et al. Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta-Analysis of Prospective Studies. J Am Heart Assoc. 2017;6(7):e004947. doi: 10.1161/JAHA.116.004947.Seldin M.M., Meng Y., Qi H. et al. Trimethylamine N-Oxide Promotes Vascular Inflammation Through Signaling of Mitogen-Activated Protein Kinase and Nuclear Factor-κB. J Am Heart Assoc. 2016;5(2):e002767. doi: 10.1161/JAHA.115.002767.Seldin M.M., Meng Y., Qi H. et al. Trimethylamine N-Oxide Promotes Vascular Inflammation Through Signaling of Mitogen-Activated Protein Kinase and Nuclear Factor-κB. J Am Heart Assoc. 2016;5(2):e002767. doi: 10.1161/JAHA.115.002767.Zhu W., Gregory J.C., Org E. et al. Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk. Cell. 2016;165(1):111-24. doi: 10.1016/j.cell.2016.02.011.Zhu W., Gregory J.C., Org E. et al. Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk. Cell. 2016;165(1):111-24. doi: 10.1016/j.cell.2016.02.011.Koren O., Spor A., Felin J. et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci USA. 2011;108(1):4592-8. doi: 10.1073/pnas.1011383107.Koren O., Spor A., Felin J. et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci USA. 2011;108(1):4592-8. doi: 10.1073/pnas.1011383107.Koren O., Spor A., Felin J. et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl AcadSci USA. 2011;108(Suppl1):4592-8. doi: 10.1073/pnas.1011383107.Koren O., Spor A., Felin J. et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl AcadSci USA. 2011;108(Suppl1):4592-8. doi: 10.1073/pnas.1011383107.Neves A.L., Coelho J., Couto L. et al. Metabolic endotoxemia: A molecular link between obesity and cardiovascular risk. J Mol Endocrinol. 2013;11;51(2):R51-64. doi: 10.1530/JME-13-0079.Neves A.L., Coelho J., Couto L. et al. Metabolic endotoxemia: A molecular link between obesity and cardiovascular risk. J Mol Endocrinol. 2013;11;51(2):R51-64. doi: 10.1530/JME-13-0079.Ohashi R., Mu H., Wang X. et al. Reverse cholesterol transport and cholesterol efflux in atherosclerosis. QJM Mon. J Assoc Physicians. 2005;98:845-56. doi: 10.1093/qjmed/hci136.Ohashi R., Mu H., Wang X. et al. Reverse cholesterol transport and cholesterol efflux in atherosclerosis. QJM Mon. J Assoc Physicians. 2005;98:845-56. doi: 10.1093/qjmed/hci136.Ahmadmehrabi S., Tang W. Gut microbiome and its role in cardiovascular diseases. Curr Opin Cardiol. 2017;32(6):761-6. doi: 10.1097/HCO.0000000000000445.Ahmadmehrabi S., Tang W. Gut microbiome and its role in cardiovascular diseases. Curr Opin Cardiol. 2017;32(6):761-6. doi: 10.1097/HCO.0000000000000445.Diehl G.E., Longman R.S., Zhang J-X, et al. Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX3CR1hi cells. Nature. 2013;494:116-20. doi: 10.1038/nature11809.Diehl G.E., Longman R.S., Zhang J-X, et al. Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX3CR1hi cells. Nature. 2013;494:116-20. doi: 10.1038/nature11809.Yamashita T., Kasahara K., Emoto T. et al. Intestinal Immunity and Gut Microbiota as Therapeutic Targets for Preventing Atherosclerotic Cardiovascular Diseases. Circ J. 2015;79(9):1882-90. doi: 10.1253/circj.CJ-15-0526.Yamashita T., Kasahara K., Emoto T. et al. Intestinal Immunity and Gut Microbiota as Therapeutic Targets for Preventing Atherosclerotic Cardiovascular Diseases. Circ J. 2015;79(9):1882-90. doi: 10.1253/circj.CJ-15-0526.Sandek A., Bauditz J., Swidsinski A., et al. Altered intestinal function in patients with chronic heart failure. J Am Coll Cardiol. 2007;50:1561-9. doi: 10.1016/j.jacc.2007.07.016.Sandek A., Bauditz J., Swidsinski A., et al. Altered intestinal function in patients with chronic heart failure. J Am Coll Cardiol. 2007;50:1561-9. doi: 10.1016/j.jacc.2007.07.016.Kitai T., Kirsop J., Tang W. et al. Exploring the Microbiome in Heart Failure. Curr Heart Fail Rep. 2016;13(2):103-9. doi: 10.1007/s11897-016-0285-9.Kitai T., Kirsop J., Tang W. et al. Exploring the Microbiome in Heart Failure. Curr Heart Fail Rep. 2016;13(2):103-9. doi: 10.1007/s11897-016-0285-9.Pasini E., Aquilani R., Testa C. et al. Pathogenic gut flora in patients with chronic heart failure. JACC Heart Fail. 2016;4:220-7. doi: 10.1016/j.jchf.2015.10.009.Pasini E., Aquilani R., Testa C. et al. Pathogenic gut flora in patients with chronic heart failure. JACC Heart Fail. 2016;4:220-7. doi: 10.1016/j.jchf.2015.10.009.Tang W.H., Wang Z., Fan Y. et al. Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol. 2014;64:1908-14. doi:10.1016/j.jacc.2014.02.617.Tang W.H., Wang Z., Fan Y. et al. Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol. 2014;64:1908-14. doi:10.1016/j.jacc.2014.02.617.Mell B., Jala V.R., Mathew A.V. et al. 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.Mell B., Jala V.R., Mathew A.V. et al. 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.Qi Y., Kim S., Richards E.M. et al. Gut Microbiota: Potential for a Unifying Hypothesis for Prevention and Treatment of Hypertension. Circ Res. 2017;120(11):1724-6. doi: 10.1161/CIRCRESAHA.117.310734.Qi Y., Kim S., Richards E.M. et al. Gut Microbiota: Potential for a Unifying Hypothesis for Prevention and Treatment of Hypertension. Circ Res. 2017;120(11):1724-6. doi: 10.1161/CIRCRESAHA.117.310734.Yang T., Santisteban M.M., Rodriquez V. et al. Gut dysbiosis is linked to hypertension. Hypertens 2015;65:1331-40.doi: 10.1161/HYPERTENSIONAHA.Yang T., Santisteban M.M., Rodriquez V. et al. Gut dysbiosis is linked to hypertension. Hypertens 2015;65:1331-40.doi: 10.1161/HYPERTENSIONAHA.Pluznick J. A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes. 2014;5(2):202-7. doi: 10.4161/gmic.27492.Pluznick J. A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes. 2014;5(2):202-7. doi: 10.4161/gmic.27492.Li J., Zhao F., Wang Y. et. al Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome. 2017;5(1):14. doi: 10.1186/s40168-016-0222-x.Li J., Zhao F., Wang Y. et. al Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome. 2017;5(1):14. doi: 10.1186/s40168-016-0222-x.Marques F.Z., Mackay C.R., Kaye D.M. Beyond gut feelings: how the gut microbiota regulates blood pressure. Nat Rev Cardiol. 2018;15(1):20-32. doi: 10.1038/nrcardio.2017.120.Marques F.Z., Mackay C.R., Kaye D.M. Beyond gut feelings: how the gut microbiota regulates blood pressure. Nat Rev Cardiol. 2018;15(1):20-32. doi: 10.1038/nrcardio.2017.120.Ufnal M., Jazwiec R., Dadlez M. et al. Trimethylamine-N-oxide: a carnitinederived metabolite that prolongs the hypertensive effect of angiotensin II in rats. Can J Cardiol. 2014;30:1700-5.doi: 10.1016 / j.cjca.2014.09.010.Ufnal M., Jazwiec R., Dadlez M. et al. Trimethylamine-N-oxide: a carnitinederived metabolite that prolongs the hypertensive effect of angiotensin II in rats. Can J Cardiol. 2014;30:1700-5.doi: 10.1016 / j.cjca.2014.09.010.Wang X., Ouyang Y., Liu J. et al. Fruit and vegetableconsumption and mortality from all causes, cardiovascular disease, and cancer: systematic review and dose-response meta-analysis of prospective cohort studies. BMJ. 2014;349:g4490. doi: 10.1136/bmj.g4490.Wang X., Ouyang Y., Liu J. et al. Fruit and vegetableconsumption and mortality from all causes, cardiovascular disease, and cancer: systematic review and dose-response meta-analysis of prospective cohort studies. BMJ. 2014;349:g4490. doi: 10.1136/bmj.g4490.Marques F.Z., Nelson E.M., Chu P.Y. et al. High fibre diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in docasalt hypertensive mice. Circulation. 2016;7:024545. doi: 10.1161/CIRCULATIONAHA.116.024545.Marques F.Z., Nelson E.M., Chu P.Y. et al. High fibre diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in docasalt hypertensive mice. Circulation. 2016;7:024545. doi: 10.1161/CIRCULATIONAHA.116.024545.Gómez-Guzmán M., Toral M., Romero M. et al. Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats. Mol Nutr Food Res. 2015;59:2326-36. doi: 10.1002/mnfr.201500290.Gómez-Guzmán M., Toral M., Romero M. et al. Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats. Mol Nutr Food Res. 2015;59:2326-36. doi: 10.1002/mnfr.201500290.Lam V., Su J., Koprowski S. et al. Intestinal microbiota determine severity of myocardial infarction in rats. FASEB J. 2012;26:1727-35. doi: 10.1096/fj.11-197921.Lam V., Su J., Koprowski S. et al. Intestinal microbiota determine severity of myocardial infarction in rats. FASEB J. 2012;26:1727-35. doi: 10.1096/fj.11-197921.Gan X.T., Ettinger G., Huang C.X. et al. Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat. Circ Heart Fail. 2014;7:491-9. doi: 10.1161/CIRCHEARTFAILURE.113.000978.Gan X.T., Ettinger G., Huang C.X. et al. Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat. Circ Heart Fail. 2014;7:491-9. doi: 10.1161/CIRCHEARTFAILURE.113.000978.Everard A., Belzer C., Geurts L. et al. Cross-talk between Akkermansiamuciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl AcadSci USA. 2013;110(22):9066-71.Everard A., Belzer C., Geurts L. et al. Cross-talk between Akkermansiamuciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl AcadSci USA. 2013;110(22):9066-71.Parnell J.A, Reimer R.A. Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am J Clin Nutr. 2009;89:1751-9. doi:10.3945/ajcn.2009.27465.Parnell J.A, Reimer R.A. Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am J Clin Nutr. 2009;89:1751-9. doi:10.3945/ajcn.2009.27465.Giacco R., Clemente G., Luongo D. et al. Effects of short-chain fructooligosaccharides on glucose and lipid metabolism in mild hypercholesterolaemic individuals. Clin Nutr. 2004;23(3):331-40. doi: 10.1016/j.clnu.2003.07.010.Giacco R., Clemente G., Luongo D. et al. Effects of short-chain fructooligosaccharides on glucose and lipid metabolism in mild hypercholesterolaemic individuals. Clin Nutr. 2004;23(3):331-40. doi: 10.1016/j.clnu.2003.07.010.Wang Z., Roberts A.B., Buffa J.A., et al. Nonlethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell. 2015;163:1585-95. doi: 10.1016/j.cell.2015.11.055.Wang Z., Roberts A.B., Buffa J.A., et al. Nonlethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell. 2015;163:1585-95. doi: 10.1016/j.cell.2015.11.055.

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