diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM12716diaendo-12716Research ArticleОбзорыReviewПерспективы применения трансплантации фекальной микробиоты у пациентов с ожирением и сахарным диабетом 2 типа с целью снижения веса и улучшения чувствительности к инсулину.Prospects for the use of fecal microbiota transplantation in obese patients with Type 2 Diabetes Mellitus for weight loss and improvement of insulin sensitivityhttps://orcid.org/0000-0001-5268-430XПокровскаяЕ. В.PokrovskayaE. V.

Покровская Елена Владиславовна, н.с.; eLibrary SPIN: 8769-5010117036, Москва, ул. Дмитрия Ульянова, д. 11

Elena V. Pokrovskaya, MD, research associate; eLibrary SPIN: 8769-5010

11, Dm. Ulyanova street, 117036 Moscow

pokrovskaya.93@mail.ruhttps://orcid.org/0000-0002-7768-4717СкляникИ. А.SklyanikI. A.

Скляник Игорь Александрович, н.с.; eLibrary SPIN: 7081-8077

Москва

Igor A. Sklyanik, MD, research associate; eLibrary SPIN: 7081-8077

Moscow

sklyanik.igor@gmail.comhttps://orcid.org/0000-0001-6612-6851ШестаковаЕ. А.ShestakovaE. A.

Шестакова Екатерина Алексеевна, к.м.н., в.н.с.; eLibrary SPIN: 1124-7600

Москва

Ekaterina A. Shestakova, MD, PhD, leading research associate; eLibrary SPIN: 1124-7600

Moscow

katiashestakova@mail.ruhttps://orcid.org/0000-0002-5057-127XШестаковаМ. В.ShestakovaM. V.

Шестакова Марина Владимировна, д.м.н., профессор, академик РАН; eLibrary SPIN: 7584-7015

Москва

Marina V. Shestakova, MD, PhD, Professor; eLibrary SPIN: 7584-7015

Moscow

nephro@endocrincentr.ruНациональный медицинский исследовательский центр эндокринологииРоссияEndocrinology Research CentreRussian Federation202021012021236541547Copyright © Покровская Е.В., Скляник И.А., Шестакова Е.А., Шестакова М.В., 20212021Покровская Е.В., Скляник И.А., Шестакова Е.А., Шестакова М.В.Pokrovskaya E.V., Sklyanik I.A., Shestakova E.A., Shestakova M.V.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/12716

В связи с неконтролируемым ростом заболеваемости ожирением и сахарным диабетом 2 типа (СД2) в последние годы проводятся многочисленные работы с целью изучения патогенетических механизмов развития этих заболеваний и разработки новых методов их профилактики и лечения. Известно, что СД2 является мультифакторным заболеванием, в развитии которого принимают участие как образ жизни и различные факторы окружающей среды, так и генетическая предрасположенность. Одновременно с этим в последние годы обсуждается теория, что одним из механизмов развития ожирения и СД2 является дисбиоз кишечника, причина развития которого состоит в количественных и качественных изменениях в кишечной микробиоте (КМ). На данный момент предложены различные методы восстановления нормального состава КМ, включающие прием пребиотиков и метабиотиков, которые стимулируют рост кишечной микрофлоры, а также пробиотиков, которые непосредственно включают в себя необходимые полезные бактерии (преимущественно Bifidobacterium и Lactobacillus). Наиболее новым и малоизученным из методов нормализации КМ является трансплантация фекальной микрофлоры (ТФМ), которая позволяет переносить в организм реципиента целое микробное сообщество, а не отдельные бактерии. В связи с вышеизложенным, данный метод воздействия на КМ представляет большой интерес для профилактики и лечения метаболических заболеваний.

Concerning the uncontrolled growth in the incidence of obesity and Type 2 Diabetes Mellitus (T2DM), numerous research have been carried out to study the pathogenetic mechanisms of progress of these diseases and development of new methods for their prevention and treatment in recent years. T2DM is known to be a multifactorial disease, in the development of which both lifestyle and various environmental factors, and genetic predisposition are involved. At the same time, in recent years, a theory has been discussed that intestinal dysbiosis, which is caused with quantitative and qualitative changes in the gut microbiota (GM) is one of the mechanisms of obesity and T2DM development. At the moment, various methods have been proposed for restoring the normal composition of GM, including the administration of prebiotics and metabiotics that stimulate the growth of gut flora, as well as probiotics, which directly include the necessary beneficial bacteria (mainly Bifidobacterium and Lactobacillus). Fecal microflora transplantation (FMT), which allows transferring an entire microbial community into the recipient's body, rather than individual bacteria is the newest and least studied method of GM normalization. In this connection, this method of GM influencing is of great interest for the prevention and treatment of metabolic diseases.

сахарный диабет 2 типаожирениемикробиота кишечникатрансплантация фекальной микрофлорыdiabetes mellitus type 2obesitygut microbiotafecal microbiota transplantationРабота выполнена в рамках государственного задания ААА-А20-120011790164-4 «Ремиссия сахарного диабета 2 типа после бариатрической хирургии: роль гормонов желудочно-кишечного тракта (инкретинов), желчных кислот и микробиоты кишечника».ReferencesBuse JB, Caprio S, Cefalu WT, et al. How Do We Define Cure of Diabetes? Diabetes Care. 2009;32(11):2133-2135. https://doi.org/10.2337/dc09-9036Buse JB, Caprio S, Cefalu WT, et al. How Do We Define Cure of Diabetes? Diabetes Care. 2009;32(11):2133-2135. https://doi.org/10.2337/dc09-9036Di Angelantonio E, Kaptoge S, Wormser D, et al. Association of Cardiometabolic Multimorbidity With Mortality. JAMA. 2015;314(1):52. https://doi.org/10.1001/jama.2015.7008Di Angelantonio E, Kaptoge S, Wormser D, et al. Association of Cardiometabolic Multimorbidity With Mortality. JAMA. 2015;314(1):52. https://doi.org/10.1001/jama.2015.7008Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157(1):107843. https://doi.org/10.1016/j.diabres.2019.107843Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157(1):107843. https://doi.org/10.1016/j.diabres.2019.107843Bellou V, Belbasis L, Tzoulaki I, Evangelou E. Risk factors for type 2 diabetes mellitus: An exposure-wide umbrella review of meta-analyses. PLoS One. 2018;13(3):e0194127. https://doi.org/10.1371/journal.pone.0194127Bellou V, Belbasis L, Tzoulaki I, Evangelou E. Risk factors for type 2 diabetes mellitus: An exposure-wide umbrella review of meta-analyses. PLoS One. 2018;13(3):e0194127. https://doi.org/10.1371/journal.pone.0194127Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet. 2014;383(9922):1068-1083. https://doi.org/10.1016/S0140-6736(13)62154-6Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet. 2014;383(9922):1068-1083. https://doi.org/10.1016/S0140-6736(13)62154-6Yu F, Han W, Zhan G, et al. Abnormal gut microbiota composition contributes to the development of type 2 diabetes mellitus in db/db mice. Aging (Albany NY). 2019;11(22):10454-10467. https://doi.org/10.18632/aging.102469Yu F, Han W, Zhan G, et al. Abnormal gut microbiota composition contributes to the development of type 2 diabetes mellitus in db/db mice. Aging (Albany NY). 2019;11(22):10454-10467. https://doi.org/10.18632/aging.102469Harsch I, Konturek P. The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus: New Insights into “Old” Diseases. Med Sci. 2018;6(2):32. https://doi.org/10.3390/medsci6020032Harsch I, Konturek P. The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus: New Insights into “Old” Diseases. Med Sci. 2018;6(2):32. https://doi.org/10.3390/medsci6020032Lazar V, Ditu L-M, Pircalabioru GG, et al. Gut Microbiota, Host Organism, and Diet Trialogue in Diabetes and Obesity. Front Nutr. 2019;6(2):32. https://doi.org/10.3389/fnut.2019.00021Lazar V, Ditu L-M, Pircalabioru GG, et al. Gut Microbiota, Host Organism, and Diet Trialogue in Diabetes and Obesity. Front Nutr. 2019;6(2):32. https://doi.org/10.3389/fnut.2019.00021Sharma S, Tripathi P. Gut microbiome and type 2 diabetes: where we are and where to go? J Nutr Biochem. 2019;63(2):101-108. https://doi.org/10.1016/j.jnutbio.2018.10.003Sharma S, Tripathi P. Gut microbiome and type 2 diabetes: where we are and where to go? J Nutr Biochem. 2019;63(2):101-108. https://doi.org/10.1016/j.jnutbio.2018.10.003Kang D-W, Adams JB, Coleman DM, et al. Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Sci Rep. 2019;9(1):5821. https://doi.org/10.1038/s41598-019-42183-0Kang D-W, Adams JB, Coleman DM, et al. Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Sci Rep. 2019;9(1):5821. https://doi.org/10.1038/s41598-019-42183-0Fung TC, Olson CA, Hsiao EY. Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci. 2017;20(2):145-155. https://doi.org/10.1038/nn.4476Fung TC, Olson CA, Hsiao EY. Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci. 2017;20(2):145-155. https://doi.org/10.1038/nn.4476Scott KP, Antoine J-M, Midtvedt T, van Hemert S. Manipulating the gut microbiota to maintain health and treat disease. Microb Ecol Heal Dis. 2015;26(2):145-155. https://doi.org/10.3402/mehd.v26.25877Scott KP, Antoine J-M, Midtvedt T, van Hemert S. Manipulating the gut microbiota to maintain health and treat disease. Microb Ecol Heal Dis. 2015;26(2):145-155. https://doi.org/10.3402/mehd.v26.25877Roberfroid M. Prebiotics: The Concept Revisited. J Nutr. 2007;137(3):830S-837S. https://doi.org/10.1093/jn/137.3.830SRoberfroid M. Prebiotics: The Concept Revisited. J Nutr. 2007;137(3):830S-837S. https://doi.org/10.1093/jn/137.3.830SAzad MAK, Sarker M, Li T, Yin J. Probiotic Species in the Modulation of Gut Microbiota: An Overview. Biomed Res Int. 2018;2018(3):1-8. https://doi.org/10.1155/2018/9478630Azad MAK, Sarker M, Li T, Yin J. Probiotic Species in the Modulation of Gut Microbiota: An Overview. Biomed Res Int. 2018;2018(3):1-8. https://doi.org/10.1155/2018/9478630Sun J, Buys NJ. Glucose- and glycaemic factor-lowering effects of probiotics on diabetes: a meta-analysis of randomised placebo-controlled trials. Br J Nutr. 2016;115(7):1167-1177. https://doi.org/10.1017/S0007114516000076Sun J, Buys NJ. Glucose- and glycaemic factor-lowering effects of probiotics on diabetes: a meta-analysis of randomised placebo-controlled trials. Br J Nutr. 2016;115(7):1167-1177. https://doi.org/10.1017/S0007114516000076Żółkiewicz J, Marzec A, Ruszczyński M, Feleszko W. Postbiotics — A Step Beyond Pre- and Probiotics. Nutrients. 2020;12(8):2189. https://doi.org/10.3390/nu12082189Żółkiewicz J, Marzec A, Ruszczyński M, Feleszko W. Postbiotics — A Step Beyond Pre- and Probiotics. Nutrients. 2020;12(8):2189. https://doi.org/10.3390/nu12082189Kuznetsova EE, Gorokhova VG, Bogorodskaya SL. The microbiota of intestine. The role in development of various pathologies. Klinicheskaya Laboratornaya Diagnostika. 2016;61(10):723-726. https://doi.org/10.18821/0869-2084-2016-61-10-723-726Kuznetsova EE, Gorokhova VG, Bogorodskaya SL. The microbiota of intestine. The role in development of various pathologies. Klinicheskaya Laboratornaya Diagnostika. 2016;61(10):723-726. https://doi.org/10.18821/0869-2084-2016-61-10-723-726Карпухин О.Ю., Хасанов Э.Р., Бикбов Б.Ш. Трансплантация фекальной микробиоты в современной клинической практике // Практическая медицина. — 2017. — No6. — С. 7-12.Karpukhin OY, Khasanov ER, Bikbov BSh. Transplantation of fecal microbiota in modern clinical practice. Prakticheskaya meditsina. 2017;(6):7-12. (In Russ.).Aron-Wisnewsky J, Clément K, Nieuwdorp M. Fecal Microbiota Transplantation: a Future Therapeutic Option for Obesity/Diabetes? Curr Diab Rep. 2019;19(8):51. https://doi.org/10.1007/s11892-019-1180-zAron-Wisnewsky J, Clément K, Nieuwdorp M. Fecal Microbiota Transplantation: a Future Therapeutic Option for Obesity/Diabetes? Curr Diab Rep. 2019;19(8):51. https://doi.org/10.1007/s11892-019-1180-zWang J-W, Kuo C-H, Kuo F-C, et al. Fecal microbiota transplantation: Review and update. J Formos Med Assoc. 2019;118(8):S23-S31. https://doi.org/10.1016/j.jfma.2018.08.011Wang J-W, Kuo C-H, Kuo F-C, et al. Fecal microbiota transplantation: Review and update. J Formos Med Assoc. 2019;118(8):S23-S31. https://doi.org/10.1016/j.jfma.2018.08.011de Groot PF, Frissen MN, de Clercq NC, Nieuwdorp M. Fecal microbiota transplantation in metabolic syndrome: History, present and future. Gut Microbes. 2017;8(3):253-267. https://doi.org/10.1080/19490976.2017.1293224de Groot PF, Frissen MN, de Clercq NC, Nieuwdorp M. Fecal microbiota transplantation in metabolic syndrome: History, present and future. Gut Microbes. 2017;8(3):253-267. https://doi.org/10.1080/19490976.2017.1293224Hasan N, Yang H. Factors affecting the composition of the gut microbiota, and its modulation. Peer J. 2019;7(3):e7502. https://doi.org/10.7717/peerj.7502Hasan N, Yang H. Factors affecting the composition of the gut microbiota, and its modulation. Peer J. 2019;7(3):e7502. https://doi.org/10.7717/peerj.7502Wilson BC, Vatanen T, Cutfield WS, O’Sullivan JM. The Super-Donor Phenomenon in Fecal Microbiota Transplantation. Front Cell Infect Microbiol. 2019;9(3):e7502. https://doi.org/10.3389/fcimb.2019.00002Wilson BC, Vatanen T, Cutfield WS, O’Sullivan JM. The Super-Donor Phenomenon in Fecal Microbiota Transplantation. Front Cell Infect Microbiol. 2019;9(3):e7502. https://doi.org/10.3389/fcimb.2019.00002Backhed F, Ding H, Wang T, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci. 2004;101(44):15718-15723. https://doi.org/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. 2004;101(44):15718-15723. https://doi.org/10.1073/pnas.0407076101Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027-1031. https://doi.org/10.1038/nature05414Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027-1031. https://doi.org/10.1038/nature05414Ridaura VK, Faith JJ, Rey FE, et al. Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice. Science (80-). 2013;341(6150):1241214. https://doi.org/10.1126/science.1241214Ridaura VK, Faith JJ, Rey FE, et al. Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice. Science (80-). 2013;341(6150):1241214. https://doi.org/10.1126/science.1241214Zhang P, Li L, Han X, et al. Fecal microbiota transplantation improves metabolism and gut microbiome composition in db/db mice. Acta Pharmacol Sin. 2020;41(5):678-685. https://doi.org/10.1038/s41401-019-0330-9Zhang P, Li L, Han X, et al. Fecal microbiota transplantation improves metabolism and gut microbiome composition in db/db mice. Acta Pharmacol Sin. 2020;41(5):678-685. https://doi.org/10.1038/s41401-019-0330-9Wang H, Lu Y, Yan Y, et al. Promising Treatment for Type 2 Diabetes: Fecal Microbiota Transplantation Reverses Insulin Resistance and Impaired Islets. Front Cell Infect Microbiol. 2020;9(5):678-685. https://doi.org/10.3389/fcimb.2019.00455Wang H, Lu Y, Yan Y, et al. Promising Treatment for Type 2 Diabetes: Fecal Microbiota Transplantation Reverses Insulin Resistance and Impaired Islets. Front Cell Infect Microbiol. 2020;9(5):678-685. https://doi.org/10.3389/fcimb.2019.00455Vrieze 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.e7. https://doi.org/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.e7. https://doi.org/10.1053/j.gastro.2012.06.031Kootte RS, Levin E, Salojärvi J, et al. Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition. Cell Metab. 2017;26(4):611-619.e6. https://doi.org/10.1016/j.cmet.2017.09.008Kootte RS, Levin E, Salojärvi J, et al. Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition. Cell Metab. 2017;26(4):611-619.e6. https://doi.org/10.1016/j.cmet.2017.09.008Yu 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. https://doi.org/10.1371/journal.pmed.1003051Yu 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. https://doi.org/10.1371/journal.pmed.1003051Wilson BC, Vatanen T, Cutfield WS, O’Sullivan JM. The Super-Donor Phenomenon in Fecal Microbiota Transplantation. Front Cell Infect Microbiol. 2019;9(3):e1003051. https://doi.org/10.3389/fcimb.2019.00002Wilson BC, Vatanen T, Cutfield WS, O’Sullivan JM. The Super-Donor Phenomenon in Fecal Microbiota Transplantation. Front Cell Infect Microbiol. 2019;9(3):e1003051. https://doi.org/10.3389/fcimb.2019.00002Sunkara T, Rawla P, Ofosu A, Gaduputi V. Fecal microbiota transplant – a new frontier in inflammatory bowel disease. J Inflamm Res. 2018;Volume 11(3):321-328. https://doi.org/10.2147/JIR.S176190Sunkara T, Rawla P, Ofosu A, Gaduputi V. Fecal microbiota transplant – a new frontier in inflammatory bowel disease. J Inflamm Res. 2018;Volume 11(3):321-328. https://doi.org/10.2147/JIR.S176190Zhang F, Cui B, He X, et al. Microbiota transplantation: concept, methodology and strategy for its modernization. Protein Cell. 2018;9(5):462-473. https://doi.org/10.1007/s13238-018-0541-8Zhang F, Cui B, He X, et al. Microbiota transplantation: concept, methodology and strategy for its modernization. Protein Cell. 2018;9(5):462-473. https://doi.org/10.1007/s13238-018-0541-8Kelly CR, Kahn S, Kashyap P, et al. Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook. Gastroenterology. 2015;149(1):223-237. https://doi.org/10.1053/j.gastro.2015.05.008Kelly CR, Kahn S, Kashyap P, et al. Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook. Gastroenterology. 2015;149(1):223-237. https://doi.org/10.1053/j.gastro.2015.05.008Gupta A, Saha S, Khanna S. Therapies to modulate gut microbiota: Past, present and future. World J Gastroenterol. 2020;26(8):777-788. https://doi.org/10.3748/wjg.v26.i8.777Gupta A, Saha S, Khanna S. Therapies to modulate gut microbiota: Past, present and future. World J Gastroenterol. 2020;26(8):777-788. https://doi.org/10.3748/wjg.v26.i8.777Wang S, Xu M, Wang W, et al. Systematic Review: Adverse Events of Fecal Microbiota Transplantation. PLoS One. 2016;11(8):e0161174. https://doi.org/10.1371/journal.pone.0161174Wang S, Xu M, Wang W, et al. Systematic Review: Adverse Events of Fecal Microbiota Transplantation. PLoS One. 2016;11(8):e0161174. https://doi.org/10.1371/journal.pone.0161174

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