Изменения кишечной микробиоты как фактор риска развития дислипидемии, атеросклероза и роль пробиотиков в их профилактике

1. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics-2016 Update: a report from the american heart association. Circulation. 2016;133:e38-e360. doi: 10.1161/cir.0000000000000350
2. Стратегические приоритеты Программы ВОЗ по сердечно-сосудистым заболеваниям. Обзор доклада ВОЗ, 2005 г. [Strategic priorities for the WHO Cardiovascular Disease Program. Revier of the 2005 WHO (In Russ.)].
3. The L. GBD 2017: A fragile world. Lancet (Lond. Engl.). 2018;392:1683. doi: 10.1016/S0140-6736(18)32858-7
4. Organization WH. Cardiovascular Disease. Availabe online: https://www.who.int/cardiovascular_diseases/about_cvd/en/ (accessed on 13 November 2019).
5. Francisco Abadia-Molina, et al. The Gut Microbiota and Its Implication in the Development of Atherosclerosis and Related. Cardiovasc Dis Nut. 2020;12(3):605. doi: 0.3390/nu12030605
6. Lau K, Srivatsav V, Rizwan A, et al. Bridging the gap between gut microbial dysbiosis and cardiovascular diseases. Nutrients. 2017;9:E859. doi: 10.3390/nu9080859
7. Wang Z, Klipfell E, Bennett BJ, et al. Intestinal flora Phosphatidylcholine metabolism contributes to cardiovascular disease. Nature. 2011;472:57-63. doi: 10.1038/nature09922
8. Drosos I, Tavridou A, Kolios G. New aspects on the metabolic role of intestinal microbiota in the development of atherosclerosis. Metabolism. 2015;64:476-81. doi: 10.1016/j.metabol.2015.01.007
9. Gregory JC, BuffaJA, OrgE, et al. Transmission of atherosclerosis susceptibility with gut microbial transplantation. J Biol Chem. 2015;290:5647-60. doi: 10.1074/jbc.M114.618249
10. Jie Z, Xia H, Zhong SL, et al. The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun. 2017;8:845. doi: 10.1038/s41467-017-00900-1
11. Kasahara K, Tanoue, T, Yamashita T, et al. Commensal bacteria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis. J Lipid Res. 2017;58:519-28. doi: 10.1194/jlr.M072165
12. Koopen AM, Groen AK, et al. Human microbiome as therapeutic intervention target to reduce cardiovascular disease risk. Curr Opin Lipidol. 2016;27:615-22. doi: 10.1097/mol.0000000000000357
13. Anbazhagan AN, Priyamvada S, Priyadarshini M. Gut microbiota in vascular disease: therapeutic target? Curr Vasc Pharmacol. 2017;15:291-5. doi: 10.2174/15701611156661701050 95834
14. Santisteban MM, Qi Y, Zubcevic J, et al. Hypertension-linked pathophysiological alterations in the gut. Circ Res. 2017;120:312-23. doi: 10.1161/circresaha.116.309006
15. Roy S, Trinchieri G. Microbiota: A key orchestrator of cancer therapy. Nat Rev Cancer. 2017;17:271-85. doi: 10.1038/nrc.2017.13
16. Miele L, Giorgio V, Alberelli MA, et al. Impact of gut microbiota on obesity, diabetes, and cardiovascular disease risk. Curr Cardiol Rep. 2015;17:120. doi: 10.1007/s11886-0150671-z
17. Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19:576-85. doi: 10.1038/nm.3145
18. Kamo T, Akazawa H, Suda W, et al. Dysbiosis and compositional alterations with aging in the gut microbiota of patients with heart failure. PLoS One. 2017;12:e0174099. doi: 10.1371/journal.pone.0174099
19. Tang WH, KitaiT, Hazen SL. Gut microbiota in cardiovascular health and disease. Circ Res. 2017;120:1183-96. doi: 10.1161/circresaha.117.309715
20. Backhed F, Ley RE, Sonnenburg JL. Host-bacterial mutualism in the human intestine. Science. 2005;307:1915-20. doi: 10.1126/science.1104816
21. D' Argenio V, Salvatore F. The role of the gut microbiome in the healthy adult status. Clin Chim Acta. 2015;451(Pt A):97-102. doi: 10.1016/j.cca.2015.01.003
22. Sender R, Fuchs S, Milo R. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell. 2016;164(3):337-40. doi: 10.1016/j.cell.2016.01.013
23. Fuller M. Determination of protein and amino acid digestibility in foods including implications of gut microbial amino acid synthesis. Br J Nutr. 2012;108:238-46. doi: 10.1017/S0007114512002279
24. Cani PD, Delzenne NM. Involvement of the gut microbiota in the development of low grade in ammation associated with obesity: focus on this neglected partner. Acta Gastroenterol Belg. 2010;73:267-9. doi: 10.4161/gmic.19625
25. Carvalho BM, Guadagnini D, Tsukumo DM, et al. Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice. Diabetologia. 2012;55:2823-34. doi: 10.1007/s00125-012-2648-4
26. Neish AS. Microbes in gastrointestinal health and disease. Gastroenterology. 2009;136:65-80. doi: 10.1053/j.gastro.2008.10.080
27. Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59-65. doi: 10.1038/nature08821
28. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012 Jun 13;486(7402):207-14. doi: 10.1038/nature11234
29. Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature. 2011;473:174-80. doi: 10.1038/nature09944
30. Peterson DA, Frank DN, Pace NR, et al. Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases. Cell Host Microbe. 2008 Jun 12;3(6):417-27. doi: 10.1016/j.chom.2008.05.001
31. Carneiro de Mur M. Nonalcoholic steatohepatitis. Clin Perspectiv Gastroenterol Hepatol. 2001;2:12-5. 
32. Emoto T, Yamashita T, Kobayashi T, et al. Characterization of gut microbiota profiles in coronary artery disease patients using data mining analysis of terminal restriction y length polymorphism: gut microbiota could be a diagnostic marker of coronary artery disease. Heart Vessels. 2017;32:39-46. doi: 10.1007/s00380-016-0841-y
33. Ойноткинова О.Ш., Никонов Е.Л., Гиоева И.З. Роль микробиоты кишечника в патогенезе дислипидемии и ассоциированных метаболических нарушений. Доказательная гастроэнтерология. 2017;6(2):29-34 [Oynotkinova OSh, Nikonov EL, GioivaI Z. The role of the gut microbiota in the pathogenesis of dyslipidemia and associated metabolic disorders. Evidence-Based Gastroenterology. 2017;6(2):29-34 (In Russ.)]. doi: 10.17116/dokgastro20176229-34
34. MacFarlane MR, Liang G, Engelking LJ, et al. Insig proteins mediate feedback inhibition of cholesterol synthesis in the intestine. J Biol Chem. 2014 Jan 24;289(4):2148-56. doi: 10.1074/jbc.M113.524041
35. Brown JM, Hazen SL. Microbial modulation of cardiovascular diseases. Native Rev Microbiol. 2018;16:171-81. doi: 10.1038/nrmicro.2017.149
36. Bergeron N, Williams PT, Lamendella R, et al. Diets high in resistant starch increase plasma levels of trimethylamine-N-oxide, a metabolite of the intestinal microbiome associated with the risk of CVD. Br J Nutr. 2016;116:2020-9. doi: 10.1017/s0007114516004165
37. Li X, Shimizu Y, Kimura I. Gut microbial metabolite short-chain fatty acids and obesity. Biosci Microbiota Food Health. 2017;36(4):135-40. doi: 10.12938/bmfh.17-010. PMID: 29038768.
38. Battson ML, Lee DM, Weir TL, et al. The gut microbiota as a novel regulator of cardiovascular function and disease. J Nutr Biochem. 2018;56:1-15. doi: 10.1016 / j.jnutbio.2017.12.010
39. Kiechl S, Egger G, Mayr M, et al. Chronic infections and the risk of carotid atherosclerosis: Prospective results from a large population study. Circulation. 2001;103:1064-70. doi: 10.1161/01.cir.103.8.1064
40. Harris K, Kassis A, Major G. Is the gut microbiota a new factor contributing to obesity and its metabolic disorders? J Obes. 2012:879151. doi: 10.1155/2012/879151
41. Neves AL, Coelho J, Couto L, et al. Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk. J Mol Endocrinol. 2013;51:R51-R64. doi: 10.1530/JME-13-0079 
42. Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868-74. doi: 10.1038/nature01323 
43. Chacon MR, Lozano-Bartolome J, Portero-Otin M, et al. The gut mycobiome composition is linked to carotid atherosclerosis. Benef Microbes. 2017;9:1-14. doi: 10.3920/bm2017.002944
44. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004;4:499-511. doi: 10.1038/nri1391
45. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783-801. doi: 10.1016/j.cell.2006.02.015 
46. Barton GM, Kagan JC. A cell biological view of Toll-like receptor function: regulation through compartmentalization. Nat Rev Immunol. 2009;9:535-42. doi: 10.1038/nri2587
47. Guzzo C, Ayer A, Basta S, et al. IL-27 enhances LPS-induced proinflammatory cytokine production via upregulation of TLR4 expression and signaling in human monocytes. J Immunol. 2012;188:864-73. doi: 10.4049/jimmunol.1101912
48. Bjorkbacka H, Kunjathoor VV, Moore KJ, et al. Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways. Nat Med. 2004;10:416-21. doi: 10.1038/nm1008
49. Laman JD, Schoneveld AH, Moll FL, et al. Significance of peptidoglycan, a proinflammatory bacterial antigen in atherosclerotic arteries and its association with vulnerable plaques. Am J Cardiol. 2002;90:119-23. doi: 10.1016/S0002-9149(02)02432-3
50. Karlsson FH, Fak F, Nookaew I, et al. Symptomatic atherosclerosis is associated with an altered gumetagenome. Nat Commun. 2012;3:1245. doi: 10.1038/ncomms2266 
51. Philpott DJ, Sorbara MT, Robertson SJ, et al. NOD proteins: regulators of inflammation in health and disease. Nat Rev Immunol. 2014;14:9-23. doi: 10.1038/nri3565
52. Kobayashi KS, Chamaillard M, Ogura Y, et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science. 2005;307:731-4. doi: 10.1126/science.1104911
53. Kanno S, Nishio H, Tanaka T, et al. Activation of an innate immune receptor, Nod1, accelerates atherogenesis in Apoe-/-mice. J Immunol. 2015;194:773-80. doi: 10.4049/jimmunol.1302841
54. Kamo T, Akazawa H, Suda W, et al. Dysbiosis and compositional alterations with aging in the gut microbiota of patients with heart failure. PLoS One. 2017;12(3):e0174099. doi: 10.1371/journal.pone.0174099
55. Tang WH, Kitai T, Hazen SL. Gut microbiota in cardiovascular health and disease. Circ Res. 2017;120(7):1183-96. doi: 10.1161/CIRCRESAHA.
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56. Lever M, George PM, Slow S, et al. Betaine and trimethylamine-N-oxide as predictors of cardiovascular outcomes show different patterns in diabetes mellitus: An observational study. PLoS ONE. 2014;9:e114969. doi: 10.1371/journal.pone.011496
57. Mafune A, Iwamoto T, Tsutsumi Y, et al. Associations among serum trimethylamine-N-oxide (TMAO) levels, kidney function and infarcted coronary artery number in patients undergoing cardiovascular surgery: a cross-sectional study. Clin Exper Nephrol. 2016;20(5):731-9. doi: 10.1007/s10157-015-1207-у
58. Senthong V, Wang Z, Li XS, et al. Intestinal microbiota-generated metabolite trimethylamine-N-oxide and 5-year mortality risk in stable coronary artery disease: the contributory role of intestinal microbiota in a COURAGE-like patient cohort. J Am Heart Assoc. 2016;5(6):e002816. doi: 10.1161/JAHA.115.002816
59. Yu D, Shu XO, Rivera ES, et al. Urinary levels of trimethylamine-N-Oxide and incident coronary heart disease: a prospective investigation among urban Chinese adults. J Am Heart Assoc. 2019;8(1):e010606. doi: 10.1161/JAHA.118.010606
60. Gimbrone MA, García-Cardeña G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circul Res. 2016;118(4):620-36. doi: 10.1161/CIRCRESAHA.115.306301
61. Liu Z, Li J, Liu H, et al. The intestinal microbiota associated with cardiac valve calcification differs from that of coronary artery disease. 
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62. Karlsson FH, Fåk F, Nookaew I, et al. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun. 2012;3(1):1245. doi: 10.1038/ncomms2266
63. Liu H, Yang C, Jing Y, et al. Ability of lactic acid bacteria isolated from mink to remove cholesterol: in vitro and in vivo studies. Can J Microbiol. 2013;59(8):563-9. doi: 10.1139/cjm-2013-0200
64. Li J, Lin S, Vanhoutte PM. Akkermansia muciniphilaprotects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in ApoE-/- mice. Circulation. 2016;133(24):2434-46. doi: 10.1161/ CIRCULATIONAHA.115.019645
65. Midtvedt T. Microbial bile acid transformation. Am J Clin Nutr. 1974;27:1341-7. doi: 10.1093/ajcn/27.11.1341
66. Lefebvre P, Cariou B, Lien F, et al. Role of bile acids and bile acid receptors in metabolic regulation. Physio Rev. 2009;89:147-91. doi: 10.1152/physrev.00010.2008
67. Ridlon JM, Harris SC, Bhowmik S, et al. Consequences of bile salt biotransformations by intestinal bacteria. Gut Microbes. 2016;7:22-39. doi: 10.1080/19490976.2015.1127483
68. Hansson GK, Robertson AK, Soderberg-Naucler C. Inflammation and atherosclerosis. Ann Rev Pathol. 2006;1:297-329. doi: 10.1146/annurev.pathol.1.110304.100100 
69. Wahlstrom A, Sayin SI, Marschall HU, et al. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. 2016;24:41-50. doi: 10.1016/j.cmet.2016.05.005 
70. Li T, Chiang JY. Bile acids as metabolic regulators. Curr Opin Gastroenterol. 2015;31:159-65. doi: 10.1097/mog.0000000000000156 
71. Szeto FL, Reardon CA, Yoon D, et al. Vitamin D receptor signaling inhibits atherosclerosis in mice. Mol Endocrinol. 2012;26:1091-101. doi: 10.1210/me.2011-1329
72. Studer E, Zhou X, Zhao R, et al. Conjugated bile acids activate the sphingosine-1-phosphate receptor 2 in primary rodent hepatocytes. Hepatology. 2012;55:267-76. doi: 10.1002/hep.24681
73. Miura K, Ohnishi H. Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20:7381-91. doi: 10.3748/wjg.v20.i23.7381
74. Fuentes MC, Lajo T, Carrión JM, Cuñé J. A randomized clinical trial evaluating a proprietary mixture of Lactobacillus plantarum strains for lowering cholesterol. Med J Nutrition Metab. 2016;9(2):125-35. doi: 10.3233/MNM-160065
75. Mukerji P, Roper JM, Stahl B, et al. Safety evaluation of AB-LIFE(®) (Lactobacillus plantarum CECT 7527, 7528 and 7529): Antibiotic resistance and 90-day repeated-dose study in rats. Food Chem Toxicol [Internet]. 2016 Jun;92:117-28. doi: 10.1016/j.fct.2016.03.018
76. Roper JM, Stahl B, Smith AB, et al. Safety evaluation of AB-LIFE® (Lactobacillus plantarum CECT 7527, 7528 and 7529): Antibiotic resistance and 90-day repeated-dose study in rats. Food Chem Toxicol. 2016 Jun;92:117-28. doi: 10.1016/j.fct.2016.03.018
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________________________________________________

1. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics-2016 Update: a report from the american heart association. Circulation. 2016;133:e38-e360. doi: 10.1161/cir.0000000000000350
2. Strategic priorities for the WHO Cardiovascular Disease Program. Revier of the 2005 WHO (In Russ.)
3. The L. GBD 2017: A fragile world. Lancet (Lond. Engl.). 2018;392:1683. doi: 10.1016/S0140-6736(18)32858-7
4. Organization WH. Cardiovascular Disease. Availabe online: https://www.who.int/cardiovascular_diseases/about_cvd/en/ (accessed on 13 November 2019).
5. Francisco Abadia-Molina, et al. The Gut Microbiota and Its Implication in the Development of Atherosclerosis and Related. Cardiovasc Dis Nut. 2020;12(3):605. doi: 0.3390/nu12030605
6. Lau K, Srivatsav V, Rizwan A, et al. Bridging the gap between gut microbial dysbiosis and cardiovascular diseases. Nutrients. 2017;9:E859. doi: 10.3390/nu9080859
7. Wang Z, Klipfell E, Bennett BJ, et al. Intestinal flora Phosphatidylcholine metabolism contributes to cardiovascular disease. Nature. 2011;472:57-63. doi: 10.1038/nature09922
8. Drosos I, Tavridou A, Kolios G. New aspects on the metabolic role of intestinal microbiota in the development of atherosclerosis. Metabolism. 2015;64:476-81. doi: 10.1016/j.metabol.2015.01.007
9. Gregory JC, BuffaJA, OrgE, et al. Transmission of atherosclerosis susceptibility with gut microbial transplantation. J Biol Chem. 2015;290:5647-60. doi: 10.1074/jbc.M114.618249
10. Jie Z, Xia H, Zhong SL, et al. The gut microbiome in atherosclerotic cardiovascular disease. Nat Commun. 2017;8:845. doi: 10.1038/s41467-017-00900-1
11. Kasahara K, Tanoue, T, Yamashita T, et al. Commensal bacteria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis. J Lipid Res. 2017;58:519-28. doi: 10.1194/jlr.M072165
12. Koopen AM, Groen AK, et al. Human microbiome as therapeutic intervention target to reduce cardiovascular disease risk. Curr Opin Lipidol. 2016;27:615-22. doi: 10.1097/mol.0000000000000357
13. Anbazhagan AN, Priyamvada S, Priyadarshini M. Gut microbiota in vascular disease: therapeutic target? Curr Vasc Pharmacol. 2017;15:291-5. doi: 10.2174/15701611156661701050 95834
14. Santisteban MM, Qi Y, Zubcevic J, et al. Hypertension-linked pathophysiological alterations in the gut. Circ Res. 2017;120:312-23. doi: 10.1161/circresaha.116.309006
15. Roy S, Trinchieri G. Microbiota: A key orchestrator of cancer therapy. Nat Rev Cancer. 2017;17:271-85. doi: 10.1038/nrc.2017.13
16. Miele L, Giorgio V, Alberelli MA, et al. Impact of gut microbiota on obesity, diabetes, and cardiovascular disease risk. Curr Cardiol Rep. 2015;17:120. doi: 10.1007/s11886-0150671-z
17. Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19:576-85. doi: 10.1038/nm.3145
18. Kamo T, Akazawa H, Suda W, et al. Dysbiosis and compositional alterations with aging in the gut microbiota of patients with heart failure. PLoS One. 2017;12:e0174099. doi: 10.1371/journal.pone.0174099
19. Tang WH, KitaiT, Hazen SL. Gut microbiota in cardiovascular health and disease. Circ Res. 2017;120:1183-96. doi: 10.1161/circresaha.117.309715
20. Backhed F, Ley RE, Sonnenburg JL. Host-bacterial mutualism in the human intestine. Science. 2005;307:1915-20. doi: 10.1126/science.1104816
21. D' Argenio V, Salvatore F. The role of the gut microbiome in the healthy adult status. Clin Chim Acta. 2015;451(Pt A):97-102. doi: 10.1016/j.cca.2015.01.003
22. Sender R, Fuchs S, Milo R. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell. 2016;164(3):337-40. doi: 10.1016/j.cell.2016.01.013
23. Fuller M. Determination of protein and amino acid digestibility in foods including implications of gut microbial amino acid synthesis. Br J Nutr. 2012;108:238-46. doi: 10.1017/S0007114512002279
24. Cani PD, Delzenne NM. Involvement of the gut microbiota in the development of low grade in ammation associated with obesity: focus on this neglected partner. Acta Gastroenterol Belg. 2010;73:267-9. doi: 10.4161/gmic.19625
25. Carvalho BM, Guadagnini D, Tsukumo DM, et al. Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice. Diabetologia. 2012;55:2823-34. doi: 10.1007/s00125-012-2648-4
26. Neish AS. Microbes in gastrointestinal health and disease. Gastroenterology. 2009;136:65-80. doi: 10.1053/j.gastro.2008.10.080
27. Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59-65. doi: 10.1038/nature08821
28. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012 Jun 13;486(7402):207-14. doi: 10.1038/nature11234
29. Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature. 2011;473:174-80. doi: 10.1038/nature09944
30. Peterson DA, Frank DN, Pace NR, et al. Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases. Cell Host Microbe. 2008 Jun 12;3(6):417-27. doi: 10.1016/j.chom.2008.05.001
31. Carneiro de Mur M. Nonalcoholic steatohepatitis. Clin Perspectiv Gastroenterol Hepatol. 2001;2:12-5. 
32. Emoto T, Yamashita T, Kobayashi T, et al. Characterization of gut microbiota profiles in coronary artery disease patients using data mining analysis of terminal restriction y length polymorphism: gut microbiota could be a diagnostic marker of coronary artery disease. Heart Vessels. 2017;32:39-46. doi: 10.1007/s00380-016-0841-y
33. Oynotkinova OSh, Nikonov EL, GioivaI Z. The role of the gut microbiota in the pathogenesis of dyslipidemia and associated metabolic disorders. Evidence-Based Gastroenterology. 2017;6(2):29-34 (In Russ.) doi: 10.17116/dokgastro20176229-34
34. MacFarlane MR, Liang G, Engelking LJ, et al. Insig proteins mediate feedback inhibition of cholesterol synthesis in the intestine. J Biol Chem. 2014 Jan 24;289(4):2148-56. doi: 10.1074/jbc.M113.524041
35. Brown JM, Hazen SL. Microbial modulation of cardiovascular diseases. Native Rev Microbiol. 2018;16:171-81. doi: 10.1038/nrmicro.2017.149
36. Bergeron N, Williams PT, Lamendella R, et al. Diets high in resistant starch increase plasma levels of trimethylamine-N-oxide, a metabolite of the intestinal microbiome associated with the risk of CVD. Br J Nutr. 2016;116:2020-9. doi: 10.1017/s0007114516004165
37. Li X, Shimizu Y, Kimura I. Gut microbial metabolite short-chain fatty acids and obesity. Biosci Microbiota Food Health. 2017;36(4):135-40. doi: 10.12938/bmfh.17-010. PMID: 29038768.
38. Battson ML, Lee DM, Weir TL, et al. The gut microbiota as a novel regulator of cardiovascular function and disease. J Nutr Biochem. 2018;56:1-15. doi: 10.1016 / j.jnutbio.2017.12.010
39. Kiechl S, Egger G, Mayr M, et al. Chronic infections and the risk of carotid atherosclerosis: Prospective results from a large population study. Circulation. 2001;103:1064-70. doi: 10.1161/01.cir.103.8.1064
40. Harris K, Kassis A, Major G. Is the gut microbiota a new factor contributing to obesity and its metabolic disorders? J Obes. 2012:879151. doi: 10.1155/2012/879151
41. Neves AL, Coelho J, Couto L, et al. Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk. J Mol Endocrinol. 2013;51:R51-R64. doi: 10.1530/JME-13-0079 
42. Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868-74. doi: 10.1038/nature01323 
43. Chacon MR, Lozano-Bartolome J, Portero-Otin M, et al. The gut mycobiome composition is linked to carotid atherosclerosis. Benef Microbes. 2017;9:1-14. doi: 10.3920/bm2017.002944
44. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004;4:499-511. doi: 10.1038/nri1391
45. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783-801. doi: 10.1016/j.cell.2006.02.015 
46. Barton GM, Kagan JC. A cell biological view of Toll-like receptor function: regulation through compartmentalization. Nat Rev Immunol. 2009;9:535-42. doi: 10.1038/nri2587
47. Guzzo C, Ayer A, Basta S, et al. IL-27 enhances LPS-induced proinflammatory cytokine production via upregulation of TLR4 expression and signaling in human monocytes. J Immunol. 2012;188:864-73. doi: 10.4049/jimmunol.1101912
48. Bjorkbacka H, Kunjathoor VV, Moore KJ, et al. Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways. Nat Med. 2004;10:416-21. doi: 10.1038/nm1008
49. Laman JD, Schoneveld AH, Moll FL, et al. Significance of peptidoglycan, a proinflammatory bacterial antigen in atherosclerotic arteries and its association with vulnerable plaques. Am J Cardiol. 2002;90:119-23. doi: 10.1016/S0002-9149(02)02432-3
50. Karlsson FH, Fak F, Nookaew I, et al. Symptomatic atherosclerosis is associated with an altered gumetagenome. Nat Commun. 2012;3:1245. doi: 10.1038/ncomms2266 
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О.Ш. Ойноткинова1–3, Е.Л. Никонов2, Т.Ю. Демидова2, А.П. Баранов2,3, Е.В. Крюков4, Е.И. Дедов2, Е.А. Каравашкина5

1 ГБУ «Научно-исследовательский институт организации здравоохранения и медицинского менеджмента» Департамента здравоохранения г. Москвы, Москва, Россия; 
2 ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия; 
3 ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова», Москва, Россия; 
4 ФГБУ «Главный военный клинический госпиталь им. Н.Н. Бурденко» Минобороны России, Москва, Россия; 
5 ФГБУ «Поликлиника №1» Управления делами Президента РФ, Москва, Россия

________________________________________________

O.S. Oynotkinova1–3, E.L. Nikonov2, T.Y. Demidova2, A.P. Baranov2,3, E.V. Kryukov4, E.I. Dedov2, E.A. Karavashkina5

1 Research Institute of the Organization of Health Care and Medical Management, Moscow, Russia;
2 Pirogov Russian National Research Medical University, Moscow, Russia;
3 Lomonosov Moscow State University, Moscow, Russia;
4 Burdenko Main Military Clinical Hospital, Moscow, Russia;
5 Polyclinic No1, Moscow, Russia