jofinЖурнал инфектологииJournal Infectology2072-6732IPO “АIDSSPbR"10.22625/2072-6732-2014-6-4-5-12jofin-349Research ArticleЛекцииLecturesДИСБАЛАНС КИШЕЧНОЙ МИКРОБИОТЫ КАК ФАКТОР РИСКА КАРДИОМЕТАБОЛИЧЕСКИХ ЗАБОЛЕВАНИЙImbalance in the intestinal microbiota as a risk factor of cardiometabolic diseasesЛобзинЮ. В.LobzinYu. V.

директор Научно-исследовательского института детских инфекций, заведующий кафедрой инфекционных болезней Северо-Западного государственного медицинского университета им. И.И. Мечникова, д.м.н., профессор, заслуженный деятель науки РФ, академик РАН; тел.: 8(812)234-60-04, факс 8(812)234-96-91

niidi@niidi.ruАвдееваМ. В.AvdeevaM. V.

доцент кафедры общественного здоровья и здравоохранения Северо-Западного государственного медицинского университета им. И.И. Мечникова, к.м.н.; тел.: 8(812)543-02-32, факс 8(812)543-13-45

Lensk69@mail.ruСидоренкоС. В.SidorenkoS. V.

руководитель отдела молекулярной микробиологии и эпидемиологии Научно-исследовательского института детских инфекций, д.м.н., профессор; тел.: 8(812)234-60-04, факс 8(812)234-96-91

sidorserg@yandex.ruЛучкевичВ. С.LuchkevichV. S.

заведующий кафедрой общественного здоровья и здравоохранения Северо-Западного государственного медицинского университета им. И.И. Мечникова, д.м.н., профессор; тел.: 8(812)543-02-32, факс 8(812)543-13-45

vladimir.luchkevich@spbmapo.ruНаучно-исследовательский институт детских инфекций, Санкт-Петербург, Россия Северо-Западный государственный медицинский университет им. И.И. Мечникова, Санкт-Петербург, РоссияРоссияScience Research Institution of Children’s Infections, Saint-Petersburg, Russia North-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg, RussiaRussian FederationСеверо-Западный государственный медицинский университет им. И.И. Мечникова, Санкт-Петербург, РоссияРоссияNorth-Western State Medical University named after I.I. Mechnikov, Saint-Petersburg, RussiaRussian FederationНаучно-исследовательский институт детских инфекций, Санкт-Петербург, РоссияРоссияScience Research Institution of Children’s Infections, Saint-Petersburg, RussiaRussian Federation20142312201464512Copyright © Лобзин Ю.В., Авдеева М.В., Сидоренко С.В., Лучкевич В.С., 20142014Лобзин Ю.В., Авдеева М.В., Сидоренко С.В., Лучкевич В.С.Lobzin Y.V., Avdeeva M.V., Sidorenko S.V., Luchkevich V.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.niidi.ru/jofin/article/view/349

В обзоре подчеркивается роль кишечной микрофлоры в развитии атеросклероза, ишемической болезни сердца, избыточного веса /ожирения и сахарного диабета. Хорошо известно, что потребление продуктов, богатых насыщенными жирами и холестерином (мяса, яичного желтка и молочных продуктов с высоким содержанием жира), связано с повышенным риском сердечно-сосудистых заболеваний. Новые исследования показывают, что атерогенные свойства этих продуктов также обусловлены высоким содержанием L-карнитина и его структурного аналога холина, которые после поступления в организм метаболизируются кишечными бактериями до триметиламина (TMA), а затем преобразуются в печени до триметиламин-N-оксида (ТМАО), обладающего прямым атерогенным действием. Оказалось, что повышенный уровень ТМАО увеличивает риск развития инфаркта миокарда, инсульта, сердечной недостаточности и смерти, в том числе от общих причин. В центре мирового внимания также находится вопрос о роли дисбаланса кишечной микробиоты в развитии инсулинорезистентности, эндотелиальной дисфункции, нарастании адгезивных свойств макрофагов, появлении дислипидемии, повышении артериального давления, увеличении веса. Внимание врачей акцентируется на том, что для предотвращения кардиометаболических заболеваний, помимо реализации уже хорошо известных и общепринятых профилактических мероприятий, крайне важно поддержание нормального баланса микробиоты кишечника.

The review shows the role of the intestinal microflora in the development of atherosclerosis, coronary heart disease, overweight / obesity and diabetes. It is well known that consumption of foods rich in saturated fats and cholesterol (meat, egg yolk and milk products with high fat content) is associated with an increased risk of cardiovascular disease. However, new studies show that the atherogenic properties of these products are also due to the high content of L-carnitine and its structural analog choline, which, after entering the body is metabolized by intestinal bacteria up to trimethylamine (TMA), and then converted in the liver to trimethylamine-N-oxide (TMAO) having direct atherogenic action. It was found that elevated levels of TMAO increases the risk of myocardial infarction, stroke, cardiac failure and death, including the common causes. In the center of international attention is also the question of the role of the intestinal microbiota imbalance in the development of insulin resistance, endothelial dysfunction, increase of the adhesive properties of macrophages, the appearance of dyslipidemia, elevated blood pressure, overweight. Attention of the doctors is focused on the extremely importance of maintaining a normal balance of the intestinal microbiota to prevent cardiometabolic diseases apart from implementation of already well-known and generally accepted preventive measures.

первичная профилактикакардио- метаболические заболеваниямикробиотамикрофлора кишечникаинфекционный фактор рискаprimary preventioncardiometabolic diseasesintestinal microflorainfectious risk factorReferencesAvdeeva M.V., Samojlova I.G., Shheglov D.S. Pathogenetics aspects of relationship mouth infectious diseases with development and progression atherosclerosis and possibility for their integrated prevention. Zhurnal infektologii. 2012; 4 (3): 30–34. (in Russian).Avdeeva M.V., Samojlova I.G., Shheglov D.S. Pathogenetics aspects of relationship mouth infectious diseases with development and progression atherosclerosis and possibility for their integrated prevention. Zhurnal infektologii. 2012; 4 (3): 30–34. (in Russian).Pan A., Sun Q., Bernstein A.M. et al. Red meat consumption and mortality: results from 2 prospective cohort studies. Arch. Intern. Med. 2012; 172: 555–63.Pan A., Sun Q., Bernstein A.M. et al. Red meat consumption and mortality: results from 2 prospective cohort studies. Arch. Intern. Med. 2012; 172: 555–63.Howitt M.R., Garrett W.S. Gut microbiota and cardiovascular disease connectivity. Nat. Med. 2012; 18 (8): 1188–89.Howitt M.R., Garrett W.S. Gut microbiota and cardiovascular disease connectivity. Nat. Med. 2012; 18 (8): 1188–89.Brown J.M., Hazen Brown S.L. Metaorganismal nutrient metabolism as a basis of cardiovascular disease. Curr. Opin. Lipidol. 2014; 25 (1): 48–53.Brown J.M., Hazen Brown S.L. Metaorganismal nutrient metabolism as a basis of cardiovascular disease. Curr. Opin. Lipidol. 2014; 25 (1): 48–53.Löster H. Carnitin and cardiovascular diseases. Bochum.: Ponte Press Verlags-GmbH., 2003.Löster H. Carnitin and cardiovascular diseases. Bochum.: Ponte Press Verlags-GmbH., 2003.Wang Z., Klipfell E., Bennett B.J. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011; 472: 57–63.Wang Z., Klipfell E., Bennett B.J. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011; 472: 57–63.Loscalzo J. Gut microbiota, the genome, and diet in atherogenesis. N. Engl. J. Med. 2013; 368: 1647–1649.Loscalzo J. Gut microbiota, the genome, and diet in atherogenesis. N. Engl. J. Med. 2013; 368: 1647–1649.Tang W.H.W., Wang Z., Levison B.S. et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 2013; 368: 1575–84.Tang W.H.W., Wang Z., Levison B.S. et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 2013; 368: 1575–84.Ley R.E., Hamady M., Lozupone C. et al. Evolution of mammals and their gut microbes. Science. 2008; 320: 1647–51.Ley R.E., Hamady M., Lozupone C. et al. Evolution of mammals and their gut microbes. Science. 2008; 320: 1647–51.Scott K.P., Gratz S.W., Sheridan P.O. et al. The influence of diet on the gut microbiota. Pharmacol. Res. 2012; 69 (1): 52–60.Scott K.P., Gratz S.W., Sheridan P.O. et al. The influence of diet on the gut microbiota. Pharmacol. Res. 2012; 69 (1): 52–60.Kuka J., Liepinsh E., Makrecka-Kuka M. et al. Suppression of intestinal microbiota-dependent production of pro-atherogenic trimethylamine N-oxide by shifting L-carnitine microbial degradation. Life Sci. 2014. Available at http://www.ncbi.nlm.nih.gov/pubmed/25301199.Kuka J., Liepinsh E., Makrecka-Kuka M. et al. Suppression of intestinal microbiota-dependent production of pro-atherogenic trimethylamine N-oxide by shifting L-carnitine microbial degradation. Life Sci. 2014. Available at http://www.ncbi.nlm.nih.gov/pubmed/25301199.Koeth R.A., Wang Z., Levison B.S. et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 2013; 19: 576–85.Koeth R.A., Wang Z., Levison B.S. et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 2013; 19: 576–85.Clarke S.F., Murphy E.F., O’Sullivan O. et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014; 63 (12): 1913−20.Clarke S.F., Murphy E.F., O’Sullivan O. et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014; 63 (12): 1913−20.Cannon J.A., McMurray J.V. Gut feelings about heart failure. J. Am. Coll. Cardiol. 2014; 64: 1915–16.Cannon J.A., McMurray J.V. Gut feelings about heart failure. J. Am. Coll. Cardiol. 2014; 64: 1915–16.Bennett B.J., de Aguiar Vallim T.Q., Wang Z. et al. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell. Metab. 2013; 17: 49–60.Bennett B.J., de Aguiar Vallim T.Q., Wang Z. et al. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell. Metab. 2013; 17: 49–60.Suzuki H., Kurihara Y., Takeya M. et al. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature. 1997; 386: 292–296.Suzuki H., Kurihara Y., Takeya M. et al. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature. 1997; 386: 292–296.Kunjathoor V.V., Febbraio M., Podrez E.A. et al. Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J. Biol. Chem. 2002; 277 (51): 49982–88.Kunjathoor V.V., Febbraio M., Podrez E.A. et al. Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J. Biol. Chem. 2002; 277 (51): 49982–88.Febbraio M., Podrez E.A., Smith J.D. et al. Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J. Clin. Invest. 2000; 105: 1049–56.Febbraio M., Podrez E.A., Smith J.D. et al. Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J. Clin. Invest. 2000; 105: 1049–56.Trauner M., Fickert P., Tilg H. Bile acids as modulators of gut microbiota linking dietary habits and inflammatory bowel disease: a potentially dangerous liaison. Gastroenterology. 2013; 144 (4): 844–46.Trauner M., Fickert P., Tilg H. Bile acids as modulators of gut microbiota linking dietary habits and inflammatory bowel disease: a potentially dangerous liaison. Gastroenterology. 2013; 144 (4): 844–46.Pluznick J.L., Protzko R.J., Gevorgyan H. et al. Olfactory receptor esponding to gut microbiota derived signals plays a role in renin secretion and blood pressure regulation. Natl. Acad. Sci. USA. 2013; 110 (11): 4410–15.Pluznick J.L., Protzko R.J., Gevorgyan H. et al. Olfactory receptor esponding to gut microbiota derived signals plays a role in renin secretion and blood pressure regulation. Natl. Acad. Sci. USA. 2013; 110 (11): 4410–15.Chen D., Yang Z., Chen X. et al. The effect of Lactobacillus rhamnosus hsryfm 1301 on the intestinal microbiota of a hyperlipidemic rat model. BMC Complement Altern. Med. 2014; 14: 386.Chen D., Yang Z., Chen X. et al. The effect of Lactobacillus rhamnosus hsryfm 1301 on the intestinal microbiota of a hyperlipidemic rat model. BMC Complement Altern. Med. 2014; 14: 386.Scheepers L.E., Penders J., Mbakwa C.A. et al. The intestinalScheepers L.E., Penders J., Mbakwa C.A. et al. The intestinalmicrobiota composition and weight development in children: the koala birth cohort study. Int. J. Obes. (Lond). 2014; 11: doi: 10.1038/ijo.2014.178.microbiota composition and weight development in children: the koala birth cohort study. Int. J. Obes. (Lond). 2014; 11: doi: 10.1038/ijo.2014.178.Woting A., Pfeiffer N., Loh G. et al. Clostridium ramosum promotes high-fat diet-induced obesity in gnotobiotic mouse models. MBio. 2014; 5: 14.Woting A., Pfeiffer N., Loh G. et al. Clostridium ramosum promotes high-fat diet-induced obesity in gnotobiotic mouse models. MBio. 2014; 5: 14.Lazebnik L.B., Konev Ju.V. New understanding of the role of the microbiota in the pathogenesis of the metabolic syndrome. Consilium medicum. 2014; 8: 77–82. (in Russian).Lazebnik L.B., Konev Ju.V. New understanding of the role of the microbiota in the pathogenesis of the metabolic syndrome. Consilium medicum. 2014; 8: 77–82. (in Russian).Cani P.D., Delzenne N.M. The gut microbiome as therapeutic target. Pharmacol. Ther. 2011; 130: 202–12.Cani P.D., Delzenne N.M. The gut microbiome as therapeutic target. Pharmacol. Ther. 2011; 130: 202–12.Vrieze A., Nood E.V., Holleman F. et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012; 143: 913–16.Vrieze A., Nood E.V., Holleman F. et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012; 143: 913–16.Everard A., Cani P.D. Diabetes, obesity and gut microbiota. Best. Pract. Res. Clin. Gastroenterol. 2013; 27: 73–83.Everard A., Cani P.D. Diabetes, obesity and gut microbiota. Best. Pract. Res. Clin. Gastroenterol. 2013; 27: 73–83.Kimura I., Ozawa K., Inoue D. et al. The gut microbiota suppresses insulin-mediated fat accumulation via the shortchain fatty acid receptor GPR43. Nat. Commun. 2013; 4: 1829.Kimura I., Ozawa K., Inoue D. et al. The gut microbiota suppresses insulin-mediated fat accumulation via the shortchain fatty acid receptor GPR43. Nat. Commun. 2013; 4: 1829.Zhao L., Shen J. Whole-body systems approaches for gut microbiota-targeted, preventive healthcare. J. Biotechnol. 2010; 149: 183–190.Zhao L., Shen J. Whole-body systems approaches for gut microbiota-targeted, preventive healthcare. J. Biotechnol. 2010; 149: 183–190.Tilg H., Moschen A.R. Microbiota and Diabetes: An Evolving Relationship. Gut. 2014; 63 (9): 1513-21.Tilg H., Moschen A.R. Microbiota and Diabetes: An Evolving Relationship. Gut. 2014; 63 (9): 1513-21.Xiao S., Zhao L. Gut microbiota-based translational biomarkers to prevent metabolic syndrome via nutritional modulation. FEMS Microbiology Ecology. 2014; 87 (2): 303–14.Xiao S., Zhao L. Gut microbiota-based translational biomarkers to prevent metabolic syndrome via nutritional modulation. FEMS Microbiology Ecology. 2014; 87 (2): 303–14.Muccioli G.G., Naslain D., Bäckhed F. et al. The endocannabinoid system links gut microbiota to adipogenesis. Mol. Syst. Biol. 2010; 6: 392.Muccioli G.G., Naslain D., Bäckhed F. et al. The endocannabinoid system links gut microbiota to adipogenesis. Mol. Syst. Biol. 2010; 6: 392.Sivapalaratnam S., Farrugia R., Nieuwdorp M. et al. Identification of candidate genes linking systemic inflammation to atherosclerosis; results of a human in vivo LPS infusion study. BMC Med. Genomic. 2011; 4: 64.Sivapalaratnam S., Farrugia R., Nieuwdorp M. et al. Identification of candidate genes linking systemic inflammation to atherosclerosis; results of a human in vivo LPS infusion study. BMC Med. Genomic. 2011; 4: 64.Mafra D., Lobo J.C., Barros A.F. et al. Role of altered intestinal microbiota in systemic inflammation and cardiovascular disease in chronic kidney disease. Future Microbiol. 2014; 9 (3): 399–410.Mafra D., Lobo J.C., Barros A.F. et al. Role of altered intestinal microbiota in systemic inflammation and cardiovascular disease in chronic kidney disease. Future Microbiol. 2014; 9 (3): 399–410.Meijers B.K., Claes K., Bammens B. et al. Р-Cresol and cardiovascular risk in mild-to-moderate kidney disease. Clin. J. Am. Soc. Nephrol. 2010; 5: 1182–89.Meijers B.K., Claes K., Bammens B. et al. Р-Cresol and cardiovascular risk in mild-to-moderate kidney disease. Clin. J. Am. Soc. Nephrol. 2010; 5: 1182–89.Yamamoto H., Tsuruoka S., Ioka T. et al. Indoxyl sulfate stimulates proliferation of rat vascular smooth muscle cells. Kidney Int. 2006; 69: 1780–85.Yamamoto H., Tsuruoka S., Ioka T. et al. Indoxyl sulfate stimulates proliferation of rat vascular smooth muscle cells. Kidney Int. 2006; 69: 1780–85.Xu H., Barnes G.T., Yang Q.et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 2003; 112: 1821–30.Xu H., Barnes G.T., Yang Q.et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 2003; 112: 1821–30.Cai D., Yuan M., Frantz D.F. et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB. Nat. Med. 2005; 11: 183–190.Cai D., Yuan M., Frantz D.F. et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB. Nat. Med. 2005; 11: 183–190.Hara T., Kimura I., Inoue D.et al. Free fatty acid receptors and their role in regulation of energy metabolism. Rev. Physiol. Biochem. Pharmacol. 2013; 164: 77–116.Hara T., Kimura I., Inoue D.et al. Free fatty acid receptors and their role in regulation of energy metabolism. Rev. Physiol. Biochem. Pharmacol. 2013; 164: 77–116.Cani P.D., Delzenne N.M. The role of the gut microbiota in energy metabolism and metabolic disease. Curr. Pharm. Des. 2009; 15: 1546–58.Cani P.D., Delzenne N.M. The role of the gut microbiota in energy metabolism and metabolic disease. Curr. Pharm. Des. 2009; 15: 1546–58.Cani P.D., Delzenne N.M. Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota. Curr. Opin. Pharmacol. 2009; 9: 737–43.Cani P.D., Delzenne N.M. Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota. Curr. Opin. Pharmacol. 2009; 9: 737–43.Kovatcheva-Datchary P., Arora Nutrition T., Nutrition, the gut microbiome and the metabolic syndrome. Best Pract. Res. Clin. Gastroenterol. 2013; 27: 59–72.Kovatcheva-Datchary P., Arora Nutrition T., Nutrition, the gut microbiome and the metabolic syndrome. Best Pract. Res. Clin. Gastroenterol. 2013; 27: 59–72.

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