diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM7704diaendo-7704Research ArticleВопросы патогенезаPathogenesisРегуляция метаболических процессов, опосредованная кишечной микрофлоройThe role of gut microbiota in metabolic regulationКравчукЕкатерина НикодимовнаKravchukEkaterina N.

MD, PhD

kravchuke@gmail.comНеймаркАлександр ЕвгеньевичNeimarkAlexander E.

к.м.н.

galagudza@almazovcentre.ruГриневаЕлена НиколаевнаGrinevaElena N.

д.м.н., директор Института эндокринологии

MD, PhD

grineva_e@mail.ruГалагудзаМихаил МихайловичGalagudzaMikhail M.

д.м.н., Директор Института экспериментальной медицины

MD, PhD

galagudza@almazovcentre.ruФГБУ Северо-Западный медицинский исследовательский центр им. В.А. Алмазова Минздрава РоссииРоссияAlmazov North-West Medical Research CentreRussian Federation201608092016194Том 19, №4(2016)280285Copyright © Кравчук Е.Н., Неймарк А.Е., Гринева Е.Н., Галагудза М.М., 20162016Кравчук Е.Н., Неймарк А.Е., Гринева Е.Н., Галагудза М.М.Kravchuk E.N., Neimark A.E., Grineva E.N., Galagudza M.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/7704

Ожирение и метаболический синдром являются одной из основных проблем современного общества. Эпидемия ожирения ассоциирована с увеличением частоты развития сахарного диабета 2 типа, сердечно-сосудистых и онкологических заболеваний. Разработке методов борьбы с ожирением и его осложнениями посвящено огромное количество научных исследований. В последние годы внимание исследователей обращено в сторону изучения кишечной микрофлоры не только как возможного участника патологического процесса, но и вероятной мишени для терапевтического воздействия. По результатам недавних исследований (в основном на животных моделях) кишечная микрофлора вносит значимый вклад не только в экстракцию питательных веществ из поступающей пищи, но и в регуляцию энергетического обмена. В данном обзоре будет рассмотрена роль кишечной микрофлоры в метаболических процессах организма человека в целом, а также новейшие разработки по коррекции нарушений, характерных для ожирения и метаболического синдрома.

Obesity and metabolic syndrome are among the major problems of modern society. The increase in obesity is associated with a corresponding increase in type 2 diabetes, cardiovascular disease and cancer. A huge amount of scientific research has been devoted to the development of methods to reduce obesity and its complications. In recent years, attention has shifted towards studying the intestinal microbiota not only as a possible component of the pathological process but also as a target of therapeutic intervention. Recent evidence, primarily from investigations in animal models, suggests that the intestinal microbiota affects nutrient acquisition and energy regulation. This review will discuss the role of the intestinal microbiota in metabolic processes as well as the latest developments on the improvement of disturbances specific to obesity and metabolic syndrome.

кишечная микрофлораожирениеметаболический синдромкороткоцепочечные жирные кислотыжелчные кислотыintestinal microbiotaobesitymetabolic syndromeshort-chain fatty acidbile acidГрант Российского научного фонда (проект №15-14-30012)Grant by Russian Science Foundation (15-14-30012)ReferencesВсемирная организация здравоохранения, Центр СМИ, Ожирение и избыточный вес, Информационный бюллетень N 311, пересмотр январь 2015 г. Available from: http://www.who.int/mediacentre/factsheets/fs311/ru/ [Worldhealthorganization, Obesityandoverweight, FactsheetN 311, Updated January 2015. Available from: http://www.who.int/mediacentre/factsheets/fs311/ru/ (in Russ)]Всемирная организация здравоохранения, Центр СМИ, Ожирение и избыточный вес, Информационный бюллетень N 311, пересмотр январь 2015 г. Available from: http://www.who.int/mediacentre/factsheets/fs311/ru/ [Worldhealthorganization, Obesityandoverweight, FactsheetN 311, Updated January 2015. Available from: http://www.who.int/mediacentre/factsheets/fs311/ru/ (in Russ)]Zhang PY. Cardiovascular disease in diabetes. Eur Rev Med Pharmacol Sci. 2014;18(15):2205-2214.Zhang PY. Cardiovascular disease in diabetes. Eur Rev Med Pharmacol Sci. 2014;18(15):2205-2214.Badrick E, Renehan AG. Diabetes and cancer: 5 years into the recent controversy. Eur J Cancer. 2014;50(12):2119-2125. doi: 10.1016/j.ejca.2014.04.032Badrick E, Renehan AG. Diabetes and cancer: 5 years into the recent controversy. Eur J Cancer. 2014;50(12):2119-2125. doi: 10.1016/j.ejca.2014.04.032Sjostrom L. Review of the key results from the Swedish Obese Subjects (SOS) trial – a prospective controlled intervention study of bariatric surgery. J Intern Med. 2013;273(3):219-234. doi: 10.1111/joim.12012Sjostrom L. Review of the key results from the Swedish Obese Subjects (SOS) trial – a prospective controlled intervention study of bariatric surgery. J Intern Med. 2013;273(3):219-234. doi: 10.1111/joim.12012Cunningham JW, Wiviott SD. Modern obesity pharmacotherapy: weighing cardiovascular risk and benefit. Clin Cardiol. 2014;37(11):693-699. doi: 10.1002/clc.22304Cunningham JW, Wiviott SD. Modern obesity pharmacotherapy: weighing cardiovascular risk and benefit. Clin Cardiol. 2014;37(11):693-699. doi: 10.1002/clc.22304Backhed F, Ding H, Wang T, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004;101(44):15718-15723. doi: 10.1073/pnas.0407076101Backhed F, Ding H, Wang T, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004;101(44):15718-15723. doi: 10.1073/pnas.0407076101von Engelhardt W, Bartels J, Kirschberger S, et al. Role of short-chain fatty acids in the hind gut. Vet Q. 1998;20(sup3):52-59. doi: 10.1080/01652176.1998.9694970von Engelhardt W, Bartels J, Kirschberger S, et al. Role of short-chain fatty acids in the hind gut. Vet Q. 1998;20(sup3):52-59. doi: 10.1080/01652176.1998.9694970Le Poul E, Loison C, Struyf S, et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem. 2003;278(28):25481-25489. doi: 10.1074/jbc.M301403200Le Poul E, Loison C, Struyf S, et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem. 2003;278(28):25481-25489. doi: 10.1074/jbc.M301403200Vangaveti V, Shashidhar V, Jarrod G, et al. Free fatty acid receptors: emerging targets for treatment of diabetes and its complications. Ther Adv Endocrinol Metab. 2010;1(4):165-175. doi: 10.1177/2042018810381066Vangaveti V, Shashidhar V, Jarrod G, et al. Free fatty acid receptors: emerging targets for treatment of diabetes and its complications. Ther Adv Endocrinol Metab. 2010;1(4):165-175. doi: 10.1177/2042018810381066Chambers ES, Viardot A, Psichas A, et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut.2015;64(11):1744-1754. doi: 10.1136/gutjnl-2014-307913Chambers ES, Viardot A, Psichas A, et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut.2015;64(11):1744-1754. doi: 10.1136/gutjnl-2014-307913Sina C, Gavrilova O, Forster M, et al. G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation. J Immunol. 2009;183(11):7514-7522. doi: 10.4049/jimmunol.0900063Sina C, Gavrilova O, Forster M, et al. G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation. J Immunol. 2009;183(11):7514-7522. doi: 10.4049/jimmunol.0900063Maslowski KM, Vieira AT, Ng A, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461(7268):1282-1286. doi: 10.1038/nature08530Maslowski KM, Vieira AT, Ng A, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461(7268):1282-1286. doi: 10.1038/nature08530Tazoe H, Otomo Y, Karaki S-i, et al. Expression of short-chain fatty acid receptor GPR41 in the human colon. Biomed Res. 2009;30(3):149-156. doi: 10.2220/biomedres.30.149Tazoe H, Otomo Y, Karaki S-i, et al. Expression of short-chain fatty acid receptor GPR41 in the human colon. Biomed Res. 2009;30(3):149-156. doi: 10.2220/biomedres.30.149Xiong Y, Miyamoto N, Shibata K, et al. Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. Proc Natl Acad Sci U S A. 2004;101(4):1045-1050. doi: 10.1073/pnas.2637002100Xiong Y, Miyamoto N, Shibata K, et al. Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. Proc Natl Acad Sci U S A. 2004;101(4):1045-1050. doi: 10.1073/pnas.2637002100Kimura I, Inoue D, Maeda T, et al. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc Natl Acad Sci U S A.2011;108(19):8030-8035. doi: 10.1073/pnas.1016088108Kimura I, Inoue D, Maeda T, et al. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc Natl Acad Sci U S A.2011;108(19):8030-8035. doi: 10.1073/pnas.1016088108Høverstad T, Midtvedt T. Short-chain fatty acids in germfree mice and rats. J Nutr. 1986;116(9):1772-1776.Høverstad T, Midtvedt T. Short-chain fatty acids in germfree mice and rats. J Nutr. 1986;116(9):1772-1776.Gao Z, Yin J, Zhang J, et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009;58(7):1509-1517. doi: 10.2337/db08-1637Gao Z, Yin J, Zhang J, et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009;58(7):1509-1517. doi: 10.2337/db08-1637Duncan SH, Belenguer A, Holtrop G, et al. Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol. 2007;73(4):1073-1078. doi: 10.1128/AEM.02340-06Duncan SH, Belenguer A, Holtrop G, et al. Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol. 2007;73(4):1073-1078. doi: 10.1128/AEM.02340-06Ichimura A, Hasegawa S, Kasubuchi M, Kimura I. Free fatty acid receptors as therapeutic targets for the treatment of diabetes. Front Pharmacol. 2014;5:236. doi: 10.3389/fphar.2014.00236Ichimura A, Hasegawa S, Kasubuchi M, Kimura I. Free fatty acid receptors as therapeutic targets for the treatment of diabetes. Front Pharmacol. 2014;5:236. doi: 10.3389/fphar.2014.00236Zhang Y, Lee FY, Barrera G, et al. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci U S A. 2006;103(4):1006-1011. doi: 10.1073/pnas.0506982103Zhang Y, Lee FY, Barrera G, et al. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci U S A. 2006;103(4):1006-1011. doi: 10.1073/pnas.0506982103Wei J, Qiu DK, Ma X. Bile acids and insulin resistance: implications for treating nonalcoholic fatty liver disease. J Dig Dis. 2009;10(2):85-90. doi: 10.1111/j.1751-2980.2009.00369.xWei J, Qiu DK, Ma X. Bile acids and insulin resistance: implications for treating nonalcoholic fatty liver disease. J Dig Dis. 2009;10(2):85-90. doi: 10.1111/j.1751-2980.2009.00369.xKawamata Y, Fujii R, Hosoya M, et al. A G protein-coupled receptor responsive to bile acids. J Biol Chem. 2003;278(11):9435-9440. doi: 10.1074/jbc.M209706200Kawamata Y, Fujii R, Hosoya M, et al. A G protein-coupled receptor responsive to bile acids. J Biol Chem. 2003;278(11):9435-9440. doi: 10.1074/jbc.M209706200Vassileva G, Golovko A, Markowitz L, et al. Targeted deletion of Gpbar1 protects mice from cholesterol gallstone formation. Biochem J. 2006;398(3):423-430. doi: 10.1042/BJ20060537Vassileva G, Golovko A, Markowitz L, et al. Targeted deletion of Gpbar1 protects mice from cholesterol gallstone formation. Biochem J. 2006;398(3):423-430. doi: 10.1042/BJ20060537Watanabe M, Houten SM, Mataki C, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature. 2006;439(7075):484-489. doi: 10.1038/nature04330Watanabe M, Houten SM, Mataki C, et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature. 2006;439(7075):484-489. doi: 10.1038/nature04330Thomas C, Gioiello A, Noriega L, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009;10(3):167-177. doi: 10.1016/j.cmet.2009.08.001Thomas C, Gioiello A, Noriega L, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009;10(3):167-177. doi: 10.1016/j.cmet.2009.08.001Keitel V. Endocrine and paracrine role of bile acids. World J Gastroenterol. 2008;14(37):5620. doi: 10.3748/wjg.14.5620Keitel V. Endocrine and paracrine role of bile acids. World J Gastroenterol. 2008;14(37):5620. doi: 10.3748/wjg.14.5620Madsen D, Beaver M, Chang L, et al. Analysis of bile acids in conventional and germfree rats. J Lipid Res. 1976;17:107–111.Madsen D, Beaver M, Chang L, et al. Analysis of bile acids in conventional and germfree rats. J Lipid Res. 1976;17:107–111.Wostmann BS. Intestinal bile acids and cholesterol absorption in the germfree rat. J Nutr. 1973;103(7):982-990.Wostmann BS. Intestinal bile acids and cholesterol absorption in the germfree rat. J Nutr. 1973;103(7):982-990.Sayin SI, Wahlstrom A, Felin J, et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab.2013;17(2):225-235. doi: 10.1016/j.cmet.2013.01.003Sayin SI, Wahlstrom A, Felin J, et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab.2013;17(2):225-235. doi: 10.1016/j.cmet.2013.01.003Turnbaugh PJ, Backhed F, Fulton L, Gordon JI. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008;3(4):213-223. doi: 10.1016/j.chom.2008.02.015Turnbaugh PJ, Backhed F, Fulton L, Gordon JI. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008;3(4):213-223. doi: 10.1016/j.chom.2008.02.015Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444(7122):1022-1023. doi: 10.1038/4441022aLey RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444(7122):1022-1023. doi: 10.1038/4441022aTurnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457(7228):480-484. doi: 10.1038/nature07540Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature. 2009;457(7228):480-484. doi: 10.1038/nature07540Duncan SH, Lobley GE, Holtrop G, et al. Human colonic microbiota associated with diet, obesity and weight loss. Int J Obes (Lond). 2008;32(11):1720-1724. doi: 10.1038/ijo.2008.155Duncan SH, Lobley GE, Holtrop G, et al. Human colonic microbiota associated with diet, obesity and weight loss. Int J Obes (Lond). 2008;32(11):1720-1724. doi: 10.1038/ijo.2008.155Schwiertz A, Taras D, Schafer K, et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring). 2010;18(1):190-195. doi: 10.1038/oby.2009.167Schwiertz A, Taras D, Schafer K, et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring). 2010;18(1):190-195. doi: 10.1038/oby.2009.167Backhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A. 2007;104(3):979-984. doi: 10.1073/pnas.0605374104Backhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A. 2007;104(3):979-984. doi: 10.1073/pnas.0605374104Rabot S, Membrez M, Bruneau A, et al. Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism. FASEB J. 2010;24(12):4948-4959. doi: 10.1096/fj.10-164921Rabot S, Membrez M, Bruneau A, et al. Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism. FASEB J. 2010;24(12):4948-4959. doi: 10.1096/fj.10-164921Santacruz A, Marcos A, Warnberg J, et al. Interplay between weight loss and gut microbiota composition in overweight adolescents. Obesity (Silver Spring). 2009;17(10):1906-1915. doi: 10.1038/oby.2009.112Santacruz A, Marcos A, Warnberg J, et al. Interplay between weight loss and gut microbiota composition in overweight adolescents. Obesity (Silver Spring). 2009;17(10):1906-1915. doi: 10.1038/oby.2009.112David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559-563. doi: 10.1038/nature12820David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559-563. doi: 10.1038/nature12820Damms-Machado A, Mitra S, Schollenberger AE, et al. Effects of surgical and dietary weight loss therapy for obesity on gut microbiota composition and nutrient absorption. Biomed Res Int.2015;2015:806248. doi: 10.1155/2015/806248Damms-Machado A, Mitra S, Schollenberger AE, et al. Effects of surgical and dietary weight loss therapy for obesity on gut microbiota composition and nutrient absorption. Biomed Res Int.2015;2015:806248. doi: 10.1155/2015/806248Vrieze 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):913-916 e917. doi: 10.1053/j.gastro.2012.06.031Vrieze 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):913-916 e917. doi: 10.1053/j.gastro.2012.06.031Sweeney TE, Morton JM. Metabolic surgery: action via hormonal milieu changes, changes in bile acids or gut microbiota? A summary of the literature. Best Pract Res Clin Gastroenterol. 2014;28(4):727-740. doi: 10.1016/j.bpg.2014.07.016Sweeney TE, Morton JM. Metabolic surgery: action via hormonal milieu changes, changes in bile acids or gut microbiota? A summary of the literature. Best Pract Res Clin Gastroenterol. 2014;28(4):727-740. doi: 10.1016/j.bpg.2014.07.016Kong LC, Tap J, Aron-Wisnewsky J, et al. Gut microbiota after gastric bypass in human obesity: increased richness and associations of bacterial genera with adipose tissue genes. Am J Clin Nutr.2013;98(1):16-24. doi: 10.3945/ajcn.113.058743Kong LC, Tap J, Aron-Wisnewsky J, et al. Gut microbiota after gastric bypass in human obesity: increased richness and associations of bacterial genera with adipose tissue genes. Am J Clin Nutr.2013;98(1):16-24. doi: 10.3945/ajcn.113.058743Liou AP, Paziuk M, Luevano JM, Jr., et al. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5(178):178ra141. doi: 10.1126/scitranslmed.3005687Liou AP, Paziuk M, Luevano JM, Jr., et al. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5(178):178ra141. doi: 10.1126/scitranslmed.3005687Damms-Machado A, Mitra S, Schollenberger AE, et al. Effects of surgical and dietary weight loss therapy for obesity on gut microbiota composition and nutrient absorption. Biomed Res Int.2015;2015:806248. doi: 10.1155/2015/806248Damms-Machado A, Mitra S, Schollenberger AE, et al. Effects of surgical and dietary weight loss therapy for obesity on gut microbiota composition and nutrient absorption. Biomed Res Int.2015;2015:806248. doi: 10.1155/2015/806248De Sa Del Fiol F, Tardelli Ferreira AC, Marciano JJ, et al. Obesity and the use of antibiotics and probiotics in rats. Chemotherapy. 2014;60(3):162-167. doi: 10.1159/000371737De Sa Del Fiol F, Tardelli Ferreira AC, Marciano JJ, et al. Obesity and the use of antibiotics and probiotics in rats. Chemotherapy. 2014;60(3):162-167. doi: 10.1159/000371737Hwang I, Park YJ, Kim YR, et al. Alteration of gut microbiota by vancomycin and bacitracin improves insulin resistance via glucagon-like peptide 1 in diet-induced obesity. FASEB J. 2015;29(6):2397-2411. doi: 10.1096/fj.14-265983Hwang I, Park YJ, Kim YR, et al. Alteration of gut microbiota by vancomycin and bacitracin improves insulin resistance via glucagon-like peptide 1 in diet-induced obesity. FASEB J. 2015;29(6):2397-2411. doi: 10.1096/fj.14-265983Dalpe-Scott M, Heick HM, Begin-Heick N. Oxytetracycline treatment improves the response to insulin in the spontaneously diabetic (BB) rat. Diabetes. 1982;31(1):53-59. doi: 10.2337/diabetes.31.1.53Dalpe-Scott M, Heick HM, Begin-Heick N. Oxytetracycline treatment improves the response to insulin in the spontaneously diabetic (BB) rat. Diabetes. 1982;31(1):53-59. doi: 10.2337/diabetes.31.1.53Thuny F, Richet H, Casalta JP, et al. Vancomycin treatment of infective endocarditis is linked with recently acquired obesity. PLoS One. 2010;5(2):e9074. doi: 10.1371/journal.pone.0009074Thuny F, Richet H, Casalta JP, et al. Vancomycin treatment of infective endocarditis is linked with recently acquired obesity. PLoS One. 2010;5(2):e9074. doi: 10.1371/journal.pone.0009074Vrieze A, Out C, Fuentes S, et al. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. J Hepatol. 2014;60(4):824-831. doi: 10.1016/j.jhep.2013.11.034Vrieze A, Out C, Fuentes S, et al. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. J Hepatol. 2014;60(4):824-831. doi: 10.1016/j.jhep.2013.11.034Попова П.В., Рязанцева Е.М., Зазерская И.Е. и др. Восстановление менструальной функции в результате терапии метформином у женщин с синдромом поликистозных яичников // Проблемы женского здоровья. – 2010. – Т. 5. – № 3. – С. 11–17. [Popova PV, Ryazantseva EM, Zazerskaya IУ, et al. Restoration of menstrual function as a result of treatment with metformin in women with polycystic ovary syndrome. Problemi genskogo zdorozia. 2010;3(5):11-17. (in Russ).]Попова П.В., Рязанцева Е.М., Зазерская И.Е. и др. Восстановление менструальной функции в результате терапии метформином у женщин с синдромом поликистозных яичников // Проблемы женского здоровья. – 2010. – Т. 5. – № 3. – С. 11–17. [Popova PV, Ryazantseva EM, Zazerskaya IУ, et al. Restoration of menstrual function as a result of treatment with metformin in women with polycystic ovary syndrome. Problemi genskogo zdorozia. 2010;3(5):11-17. (in Russ).]

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