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Подходы к изучению влияния кишечной микробиоты на развитие метаболических нарушений
Шестакова Е.А., Покровская Е.В., Самсонова М.Д. Подходы к изучению влияния кишечной микробиоты на развитие метаболических нарушений. Consilium Medicum. 2021;23(12):905–909.
DOI: 10.26442/20751753.2021.12.201289
DOI: 10.26442/20751753.2021.12.201289
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Shestakova EA, Pokrovskaya EV, Samsonova MD. Different approaches to change gut microbiota and its influence on metabolic disorders. Consilium Medicum. 2021;23(12):905–909. DOI: 10.26442/20751753.2021.12.201289
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Аннотация
Ожирение и сахарный диабет 2-го типа (СД 2) – две неинфекционные пандемии XXI в. Несмотря на большое количество исследований, посвященных причинам развития ожирения и СД 2, преодолеть неуклонный рост числа заболевших не удается. В этих условиях необходим поиск новых подходов к профилактике и лечению нарушений углеводного обмена. Одним из таких подходов является изучение механизмов воздействия кишечной микробиоты на развитие нарушений углеводного и липидного обмена. Данный обзор посвящен исследованиям, описывающим роль микробиоты в формировании ожирения и нарушений углеводного обмена. Цель обзора – описать различные подходы к изменению состава кишечной микробиоты и определить их влияние на метаболические риски. Для оценки роли изменения состава микробиоты в развитии ожирения и СД 2 нами рассмотрен ряд исследований, посвященных хронологии возникновения этих процессов в различных ситуациях. В обзор включены исследования по оценке влияния на состав микробиоты медикаментозного лечения, бариатрических оперативных вмешательств, а также трансплантации кишечной микробиоты. Также представлены данные о возможном метаболически протективном составе кишечной микробиоты.
Ключевые слова: ожирение, сахарный диабет 2-го типа, кишечная микробиота, трансплантация кишечной микробиоты, антибиотики, ингибиторы протонной помпы, бариатрическая хирургия
Ключевые слова: ожирение, сахарный диабет 2-го типа, кишечная микробиота, трансплантация кишечной микробиоты, антибиотики, ингибиторы протонной помпы, бариатрическая хирургия
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Obesity and type 2 diabetes mellitus (T2D) are two non-infectious pandemics of the XXI century. Despite a large number of studies devoted to the development of obesity and T2D, it seems complicated to overcome the ongoing growth in the number of cases. In these situations it is necessary to investigate new approaches for the prevention and treatment of such diseases. One of these approaches is to study the role of gut microbiota in the disturbance of carbohydrate and lipid metabolism. This manuscript describes the role of the microbiota in obesity and T2D. The aim of the review was to describe various approaches to change the composition of the gut microbiota and to determine its impact on metabolic risks. To assess the relationship between T2D development and changes of microbiota composition we considered a number of studies devoted to the consequence of these pathophysiologic mechanisms in various situations: the effect of drug treatment, bariatric surgery and microbiota transplantation. Possible metabolically protective gut microbiota composition is discussed.
Keywords: obesity, diabetes mellitus type 2, gut microbiota, fecal microbiota transplantation, antibiotics, proton pump inhibitors, bariatric surgery
Полный текст
Список литературы
1. Шестакова Е.А., Лунина Е.Ю., Галстян Г.Р., и др. Распространенность нарушений углеводного обмена у лиц с различными сочетаниями факторов риска сахарного диабета 2 типа в когорте пациентов исследования NATION. Сахарный диабет. 2020;23(1):4-11 [Shestakova EA, Lunina EY, Galstyan GR, et al. Type 2 diabetes and prediabetes preavalance in patients with different risk factor combinations in THE NATION study. Diabetes Mellitus. 2020;23(1):4-11 (in Russian)].
DOI:10.14341/DM12286
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6. Демидова Т.Ю., Лобанова К.Г., Ойноткинова О.Ш. Кишечная микробиота как фактор риска развития ожирения и сахарного диабета 2-го типа. Терапевтический архив. 2020;92(10):97-104 [Demidova TY, Lobanova KG, Oinotkinova OS. Gut microbiota is a factor of risk for obesity and type 2 diabetes. Terapevticheskii Arkhiv (Ter. Arkh.). 2020;92(10):97-104 (in Russian)]. DOI:10.26442/00403660.2020.10.000778
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11. Shoaie S, Ghaffari P, Kovatcheva-Datchary P, et al. Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome. Cell Metab. 2015;22(2):320-31. DOI:10.1016/j.cmet.2015.07.001
12. Wu L, Zeng T, Zinellu A, et al. A Cross-Sectional Study of Compositional and Functional Profiles of Gut Microbiota in Sardinian Centenarians. mSystems. 2019;4(4):e00325-19. DOI:10.1128/mSystems.00325-19
13. Langdon A, Crook N, Dantas G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome Med. 2016;8(1):39. DOI:10.1186/s13073-016-0294-z
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15. Mikkelsen KH, Allin KH, Knop FK. Effect of antibiotics on gut microbiota, glucose metabolism and body weight regulation: a review of the literature. Diabetes Obes Metab. 2016;18(5):444-53. DOI:10.1111/dom.12637
16. Leong KSW, McLay J, Derraik JGB, et al. Associations of Prenatal and Childhood Antibiotic Exposure With Obesity at Age 4 Years. JAMA Netw Open. 2020;3(1):e1919681. DOI:10.1001/jamanetworkopen.2019.19681
17. Singh A, Cresci GA, Kirby DF. Proton Pump Inhibitors: Risks and Rewards and Emerging Consequences to the Gut Microbiome. Nutr Clin Pract. 2018;33(5):614-24. DOI:10.1002/ncp.10181
18. Hafiz RA, Wong C, Paynter S, et al. The Risk of Community-Acquired Enteric Infection in Proton Pump Inhibitor Therapy: Systematic Review and Meta-analysis. Ann Pharmacother. 2018;52(7):613-22. DOI:10.1177/1060028018760569
19. Yuan J, He Q, Nguyen LH, et al. Regular use of proton pump inhibitors and risk of type 2 diabetes: results from three prospective cohort studies. Gut. 2020;70(6):1070-7. DOI:10.1136/gutjnl-2020-322557
20. Pareek M, Schauer PR, Kaplan LM, et al. Metabolic Surgery: Weight Loss, Diabetes, and Beyond. J Am Coll Cardiol. 2018;71(6):670-87. DOI:10.1016/j.jacc.2017.12.014
21. Wolfe BM, Kvach E, Eckel RH. Treatment of Obesity: Weight Loss and Bariatric Surgery. Circ Res. 2016;118(11):1844-55. DOI:10.1161/CIRCRESAHA.116.307591
22. Ciobârcă D, Cătoi AF, Copăescu C, et al. Bariatric Surgery in Obesity: Effects on Gut Microbiota and Micronutrient Status. Nutrients. 2020;12(1):235. DOI:10.3390/nu12010235
23. Celiker H. A new proposed mechanism of action for gastric bypass surgery: Air hypothesis. Med Hypotheses. 2017;107:81-9. DOI:10.1016/j.mehy.2017.08.012
24. Ridaura VK, Faith JJ, Rey FE, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341(6150):1241214. DOI:10.1126/science.1241214
25. Proença IM, Allegretti JR, Bernardo WM, et al. Fecal microbiota transplantation improves metabolic syndrome parameters: systematic review with meta-analysis based on randomized clinical trials. Nutr Res. 2020;83:1-14. DOI:10.1016/j.nutres.2020.06.018
26. Mocanu V, Zhang Z, Deehan EC, et al. Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial. Nat Med. 2021;27:1272-9. DOI:10.1038/s41591-021-01399-2
27. Allegretti JR, Kassam Z, Hurtado J, et al. Impact of fecal microbiota transplantation with capsules on the prevention of metabolic syndrome among patients with obesity. Hormones (Athens). 2021;20(1):209-11. DOI:10.1007/s42000-020-00265-z
28. Yu EW, Gao L, Stastka P, et al. Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial. PLoS Med. 2020;17(3):e1003051. DOI:10.1371/journal.pmed.1003051
29. Allegretti JR, Kassam Z, Mullish BH, at al. Effects of Fecal Microbiota Transplantation With Oral Capsules in Obese Patients. Clin Gastroenterol Hepatol. 2020;18(4):855-63.e2. DOI:10.1016/j.cgh.2019.07.006
30. Kim B, Choi HN, Yim JE. Effect of Diet on the Gut Microbiota Associated with Obesity. J Obes Metab Syndr. 2019;28(4):216-24. DOI:10.7570/jomes.2019.28.4.216
31. Gurung M, Li Z, You H, et al. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine. 2020;51:1025907. DOI:10.1016/j.ebiom.2019.11.051
32. Rajilić-Stojanović M, de Vos WM. The first 1000 cultured species of the human gastrointestinal microbiota. FEMS Microbiol Rev. 2014;38(5):996-1047.
DOI:10.1111/1574-6976.12075
33. Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59-65. DOI:10.1038/nature08821
34. Leylabadlo HE, Sanaie S, Heravi FS, et al. From role of gut microbiota to microbial-based therapies in type 2-diabetes. Infect Genet Evol. 2020;81:104268. DOI:10.1016/j.meegid.2020.104268
35. Sikalidis AK, Maykish A. The Gut Microbiome and Type 2 Diabetes Mellitus: Discussing a Complex Relationship. Biomedicines. 2020;8(1):8. DOI:10.3390/biomedicines8010008
36. Egshatyan L, Kashtanova D, Popenko A, et al. Gut microbiota and diet in patients with different glucose tolerance. Endocr Connect. 2016;5(1):1-9. DOI:10.1530/EC-15-0094
37. Hjorth MF, Christensen L, Kjølbæk L, et al. Pretreatment Prevotella-to-Bacteroides ratio and markers of glucose metabolism as prognostic markers for dietary weight loss maintenance. Eur J Clin Nutr. 2020;74(2):338-47. DOI:10.1038/s41430-019-0466-1
38. Roager HM, Licht TR, Poulsen SK, et al. Microbial enterotypes, inferred by the prevotella-to-bacteroides ratio, remained stable during a 6-month randomized controlled diet intervention with the new nordic diet. Appl Environ Microbiol. 2014;80(3):1142-9. DOI:10.1128/AEM.03549-13
39. Halawa MR, El-Salam MA, Mostafa BM, Sallout SS. The Gut Microbiome, Lactobacillus acidophilus; Relation with Type 2 Diabetes Mellitus. Curr Diabetes Rev. 2019;15(6):480-5. DOI:10.2174/1573399815666190206162143
40. Ferrarese R, Ceresola ER, Preti A, Canducci F. Probiotics, prebiotics and synbiotics for weight loss and metabolic syndrome in the microbiome era. Eur Rev Med Pharmacol Sci. 2018;22(21):7588-605. DOI:10.26355/eurrev_201811_16301
41. Gomes JMG, Costa JA, Alfenas RCG. Metabolic endotoxemia and diabetes mellitus: A systematic review. Metabolism. 2017;68:133-44. DOI:10.1016/j.metabol.2016.12.009
DOI:10.14341/DM12286
2. Hills RD Jr, Pontefract BA, Mishcon HR, et al. Gut Microbiome: Profound Implications for Diet and Disease. Nutrients. 2019;11(7):1613. DOI:10.3390/nu11071613
3. Mohajeri MH, Brummer RJM, Rastall RA, et al. The role of the microbiome for human health: from basic science to clinical applications. Eur J Nutr. 2018;57(Suppl. 1):1-14. DOI:10.1007/s00394-018-1703-4
4. Singh RK, Chang HW, Yan D, et al. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017;15(1):73. DOI:10.1186/s12967-017-1175-y
5. Кравчук Е.Н., Неймарк А.Е., Гринева Е.Н., и др. Регуляция метаболических процессов, опосредованная кишечной микрофлорой. Сахарный диабет. 2016;19(4):280-5 [Kravchuk EN, Neimark AE, Grineva EN, et al. The role of gut microbiota in metabolic regulation. Diabetes Mellitus. 2016;19(4):280-5 (in Russian)].
6. Демидова Т.Ю., Лобанова К.Г., Ойноткинова О.Ш. Кишечная микробиота как фактор риска развития ожирения и сахарного диабета 2-го типа. Терапевтический архив. 2020;92(10):97-104 [Demidova TY, Lobanova KG, Oinotkinova OS. Gut microbiota is a factor of risk for obesity and type 2 diabetes. Terapevticheskii Arkhiv (Ter. Arkh.). 2020;92(10):97-104 (in Russian)]. DOI:10.26442/00403660.2020.10.000778
7. Barko PC, McMichael MA, Swanson KS, et al. The Gastrointestinal Microbiome: A Review. J Vet Intern Med. 2018;32(1):9-25. DOI:10.1111/jvim.14875
8. Janda JM, Abbott SL. 16S rRNA gene sequencing for bacterial identification in the diagnostic laboratory: pluses, perils, and pitfalls. J Clin Microbiol. 2007;45(9):2761-4. DOI:10.1128/JCM.01228-07
9. Lee YY, Hassan SA, Ismail IH, et al. Gut microbiota in early life and its influence on health and disease: A position paper by the Malaysian Working Group on Gastrointestinal Health. J Paediatr Child Health. 2017;53(12):1152-8. DOI:10.1111/jpc.13640
10. Mangiola F, Nicoletti A, Gasbarrini A, Ponziani FR. Gut microbiota and aging. Eur Rev Med Pharmacol Sci. 2018;22(21):7404-13. DOI:10.26355/eurrev_201811_16280
11. Shoaie S, Ghaffari P, Kovatcheva-Datchary P, et al. Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome. Cell Metab. 2015;22(2):320-31. DOI:10.1016/j.cmet.2015.07.001
12. Wu L, Zeng T, Zinellu A, et al. A Cross-Sectional Study of Compositional and Functional Profiles of Gut Microbiota in Sardinian Centenarians. mSystems. 2019;4(4):e00325-19. DOI:10.1128/mSystems.00325-19
13. Langdon A, Crook N, Dantas G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome Med. 2016;8(1):39. DOI:10.1186/s13073-016-0294-z
14. Partap U, Allcock SH, Parker E, et al. Association between early life antibiotic use and childhood overweight and obesity: a narrative review. Glob Health Epidemiol Genom. 2018;3:e18. DOI:10.1017/gheg.2018.16
15. Mikkelsen KH, Allin KH, Knop FK. Effect of antibiotics on gut microbiota, glucose metabolism and body weight regulation: a review of the literature. Diabetes Obes Metab. 2016;18(5):444-53. DOI:10.1111/dom.12637
16. Leong KSW, McLay J, Derraik JGB, et al. Associations of Prenatal and Childhood Antibiotic Exposure With Obesity at Age 4 Years. JAMA Netw Open. 2020;3(1):e1919681. DOI:10.1001/jamanetworkopen.2019.19681
17. Singh A, Cresci GA, Kirby DF. Proton Pump Inhibitors: Risks and Rewards and Emerging Consequences to the Gut Microbiome. Nutr Clin Pract. 2018;33(5):614-24. DOI:10.1002/ncp.10181
18. Hafiz RA, Wong C, Paynter S, et al. The Risk of Community-Acquired Enteric Infection in Proton Pump Inhibitor Therapy: Systematic Review and Meta-analysis. Ann Pharmacother. 2018;52(7):613-22. DOI:10.1177/1060028018760569
19. Yuan J, He Q, Nguyen LH, et al. Regular use of proton pump inhibitors and risk of type 2 diabetes: results from three prospective cohort studies. Gut. 2020;70(6):1070-7. DOI:10.1136/gutjnl-2020-322557
20. Pareek M, Schauer PR, Kaplan LM, et al. Metabolic Surgery: Weight Loss, Diabetes, and Beyond. J Am Coll Cardiol. 2018;71(6):670-87. DOI:10.1016/j.jacc.2017.12.014
21. Wolfe BM, Kvach E, Eckel RH. Treatment of Obesity: Weight Loss and Bariatric Surgery. Circ Res. 2016;118(11):1844-55. DOI:10.1161/CIRCRESAHA.116.307591
22. Ciobârcă D, Cătoi AF, Copăescu C, et al. Bariatric Surgery in Obesity: Effects on Gut Microbiota and Micronutrient Status. Nutrients. 2020;12(1):235. DOI:10.3390/nu12010235
23. Celiker H. A new proposed mechanism of action for gastric bypass surgery: Air hypothesis. Med Hypotheses. 2017;107:81-9. DOI:10.1016/j.mehy.2017.08.012
24. Ridaura VK, Faith JJ, Rey FE, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341(6150):1241214. DOI:10.1126/science.1241214
25. Proença IM, Allegretti JR, Bernardo WM, et al. Fecal microbiota transplantation improves metabolic syndrome parameters: systematic review with meta-analysis based on randomized clinical trials. Nutr Res. 2020;83:1-14. DOI:10.1016/j.nutres.2020.06.018
26. Mocanu V, Zhang Z, Deehan EC, et al. Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial. Nat Med. 2021;27:1272-9. DOI:10.1038/s41591-021-01399-2
27. Allegretti JR, Kassam Z, Hurtado J, et al. Impact of fecal microbiota transplantation with capsules on the prevention of metabolic syndrome among patients with obesity. Hormones (Athens). 2021;20(1):209-11. DOI:10.1007/s42000-020-00265-z
28. Yu EW, Gao L, Stastka P, et al. Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial. PLoS Med. 2020;17(3):e1003051. DOI:10.1371/journal.pmed.1003051
29. Allegretti JR, Kassam Z, Mullish BH, at al. Effects of Fecal Microbiota Transplantation With Oral Capsules in Obese Patients. Clin Gastroenterol Hepatol. 2020;18(4):855-63.e2. DOI:10.1016/j.cgh.2019.07.006
30. Kim B, Choi HN, Yim JE. Effect of Diet on the Gut Microbiota Associated with Obesity. J Obes Metab Syndr. 2019;28(4):216-24. DOI:10.7570/jomes.2019.28.4.216
31. Gurung M, Li Z, You H, et al. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine. 2020;51:1025907. DOI:10.1016/j.ebiom.2019.11.051
32. Rajilić-Stojanović M, de Vos WM. The first 1000 cultured species of the human gastrointestinal microbiota. FEMS Microbiol Rev. 2014;38(5):996-1047.
DOI:10.1111/1574-6976.12075
33. Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59-65. DOI:10.1038/nature08821
34. Leylabadlo HE, Sanaie S, Heravi FS, et al. From role of gut microbiota to microbial-based therapies in type 2-diabetes. Infect Genet Evol. 2020;81:104268. DOI:10.1016/j.meegid.2020.104268
35. Sikalidis AK, Maykish A. The Gut Microbiome and Type 2 Diabetes Mellitus: Discussing a Complex Relationship. Biomedicines. 2020;8(1):8. DOI:10.3390/biomedicines8010008
36. Egshatyan L, Kashtanova D, Popenko A, et al. Gut microbiota and diet in patients with different glucose tolerance. Endocr Connect. 2016;5(1):1-9. DOI:10.1530/EC-15-0094
37. Hjorth MF, Christensen L, Kjølbæk L, et al. Pretreatment Prevotella-to-Bacteroides ratio and markers of glucose metabolism as prognostic markers for dietary weight loss maintenance. Eur J Clin Nutr. 2020;74(2):338-47. DOI:10.1038/s41430-019-0466-1
38. Roager HM, Licht TR, Poulsen SK, et al. Microbial enterotypes, inferred by the prevotella-to-bacteroides ratio, remained stable during a 6-month randomized controlled diet intervention with the new nordic diet. Appl Environ Microbiol. 2014;80(3):1142-9. DOI:10.1128/AEM.03549-13
39. Halawa MR, El-Salam MA, Mostafa BM, Sallout SS. The Gut Microbiome, Lactobacillus acidophilus; Relation with Type 2 Diabetes Mellitus. Curr Diabetes Rev. 2019;15(6):480-5. DOI:10.2174/1573399815666190206162143
40. Ferrarese R, Ceresola ER, Preti A, Canducci F. Probiotics, prebiotics and synbiotics for weight loss and metabolic syndrome in the microbiome era. Eur Rev Med Pharmacol Sci. 2018;22(21):7588-605. DOI:10.26355/eurrev_201811_16301
41. Gomes JMG, Costa JA, Alfenas RCG. Metabolic endotoxemia and diabetes mellitus: A systematic review. Metabolism. 2017;68:133-44. DOI:10.1016/j.metabol.2016.12.009
________________________________________________
1. Shestakova EA, Lunina EY, Galstyan GR, et al. Type 2 diabetes and prediabetes preavalance in patients with different risk factor combinations in THE NATION study. Diabetes Mellitus. 2020;23(1):4-11 (in Russian). DOI:10.14341/DM12286
2. Hills RD Jr, Pontefract BA, Mishcon HR, et al. Gut Microbiome: Profound Implications for Diet and Disease. Nutrients. 2019;11(7):1613. DOI:10.3390/nu11071613
3. Mohajeri MH, Brummer RJM, Rastall RA, et al. The role of the microbiome for human health: from basic science to clinical applications. Eur J Nutr. 2018;57(Suppl. 1):1-14. DOI:10.1007/s00394-018-1703-4
4. Singh RK, Chang HW, Yan D, et al. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017;15(1):73. DOI:10.1186/s12967-017-1175-y
5. Kravchuk EN, Neimark AE, Grineva EN, et al. The role of gut microbiota in metabolic regulation. Diabetes Mellitus. 2016;19(4):280-5 (in Russian).
6. Demidova TY, Lobanova KG, Oinotkinova OS. Gut microbiota is a factor of risk for obesity and type 2 diabetes. Terapevticheskii Arkhiv (Ter. Arkh.). 2020;92(10):97-104 (in Russian). DOI:10.26442/00403660.2020.10.000778
7. Barko PC, McMichael MA, Swanson KS, et al. The Gastrointestinal Microbiome: A Review. J Vet Intern Med. 2018;32(1):9-25. DOI:10.1111/jvim.14875
8. Janda JM, Abbott SL. 16S rRNA gene sequencing for bacterial identification in the diagnostic laboratory: pluses, perils, and pitfalls. J Clin Microbiol. 2007;45(9):2761-4. DOI:10.1128/JCM.01228-07
9. Lee YY, Hassan SA, Ismail IH, et al. Gut microbiota in early life and its influence on health and disease: A position paper by the Malaysian Working Group on Gastrointestinal Health. J Paediatr Child Health. 2017;53(12):1152-8. DOI:10.1111/jpc.13640
10. Mangiola F, Nicoletti A, Gasbarrini A, Ponziani FR. Gut microbiota and aging. Eur Rev Med Pharmacol Sci. 2018;22(21):7404-13. DOI:10.26355/eurrev_201811_16280
11. Shoaie S, Ghaffari P, Kovatcheva-Datchary P, et al. Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome. Cell Metab. 2015;22(2):320-31. DOI:10.1016/j.cmet.2015.07.001
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Авторы
Е.А. Шестакова*1, Е.В. Покровская1, М.Д. Самсонова2
1 ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России, Москва, Россия;
2 ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова», Москва, Россия
*katiashestakova@mail.ru
1 ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России, Москва, Россия;
2 ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова», Москва, Россия
*katiashestakova@mail.ru
________________________________________________
Ekaterina A. Shestakova*1, Elena V. Pokrovskaya1, Margarita D. Samsonova2
1 Endocrinology Research Centre, Moscow, Russia;
2 Lomonosov Moscow State University, Moscow, Russia
*katiashestakova@mail.ru
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