Дисфункция филометаболического ядра микробиоты в патогенезе сахарного диабета 2-го типа

Демидова Т.Ю., Ардатская М.Д. Дисфункция филометаболического ядра микробиоты в патогенезе сахарного диабета 2-го типа. FOCUS Эндокринология. 2021; 3: 16–23. DOI: 10.47407/ef2021.2.3.0030

Demidova T.Yu., Ardatskaya M.D. The phylometabolic core of intestinal microbiota dysfunction in the pathogenesis of diabetes mellitus. FOCUS Endocrinology. 2021; 3: 16–23. DOI: 10.47407/ef2021.2.3.0030
Филометаболическое ядро – набор эволюционно стабильных видов микроорганизмов, отвечающих за большинство основных метаболических функций кишечной микробиоты. Дисфункция филометаболического ядра, проявляющаяся нарушением соотношения его основных компонентов и качественным и количественным изменением концентраций их ключевых метаболитов, является фактором возникновения и прогрессирования многих заболеваний, в том числе сахарного диабета 2-го типа (СД 2). В обзорной статье представлены актуальные клинические данные, свидетельствующие о перспективности применения пищевых волокон для коррекции нарушений микробиоты и улучшения течения СД 2. Частично гидролизованные пищевые волокна циамопсиса в составе препарата ОптиФайбер оказывают модулирующее воздействие на баланс ключевой микробиоты и способствуют восстановлению ее нормальной метаболической функции, обеспечивая тем самым коррекцию обменных процессов, повышение чувствительности тканей к инсулину, снижение постпрандиальной гликемии и облегчение течения заболевания в целом.

Ключевые слова: микробиота, филометаболическое ядро, метаболический дисбиоз, короткоцепочечные жирные кислоты, пищевые во-локна, циамопсис, сахарный диабет 2-го типа.
Демидова Татьяна Юльевна - д-р мед. наук, проф., зав. каф. эндокринологии лечебного факультета ФГАОУ ВО «РНИМУ им. Н.И. Пирогова». E-mail: t.y.demidova@gmail.com; ORCID: 0000-0001-6385-540X; eLIBRARY.RU SPIN: 9600-9796; Scopus Author ID: 7003771623
Ардатская Мария Дмитриевна - д-р мед. наук, проф., ФГБУ ДПО ЦГМА УД Президента РФ
1. Martínez I, Muller CE, Walter J. Long-term temporal analysis of the human fecal microbiota revealed a stable core of dominant bacterial species. PLoS One 2013; 8 (7): e69621. 
2. Qin J, Li R, Raes J et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010; 464 (7285): 59–65. 
3. Reichardt N, Duncan SH, Young P, Belenguer A et al. Phylogenetic distribu-tion of three pathways for propionate production within the human gut mi-crobiota. ISME J 2014; 8 (6): 1323–35.
4. Ситкин С.И., Ткаченко Е.И., Вахитов Т.Я. Филометаболическое ядро микробиоты кишечника. Альманах клинической медицины. 2015; 40: 12–34. 
[Sitkin S.I., Tkachenko E.I., Vakhitov T.Ya. Phylometabolic core of intestinal microbiota. Almanac of Clinical Medicine. 2015; 40:12–34 (in Russian)].
5. Zhang J, Guo Z, Xue Z et al. A phylo-functional core of gut microbiota in healthy young Chinese cohorts across lifestyles, geography and ethnicities. ISME J 2015; 9 (9): 1979–90. 
6. Dai ZL, Wu G, Zhu WY. Amino acid metabolism in intestinal bacteria: links between gut ecology and host health. Front Biosci (Landmark Ed) 2011; 16: 1768–86.
7. Yu LC, Wang JT, Wei SC, Ni YH. Host-microbial interactions and regulation of intestinal epithelial barrier function: From physiology to pathology. World J Gastrointest Pathophysiol 2012; 3 (1): 27–43. 
8. Shafquat A, Joice R, Simmons SL, Huttenhower C. Functional and phyloge-netic assembly of microbial communities in the human microbiome. Trends Microbiol 2014; 22 (5): 261–6. 
9. Neis EP, Dejong CH, Rensen SS. The role of microbial amino acid metabolism in host metabolism. Nutrients 2015; 7 (4): 2930–46. 
10. Marín L, Miguélez EM, Villar CJ, Lombó F. Bioavailability of dietary polyphe-nols and gut microbiota metabolism: antimicrobial properties. Biomed Res Int 2015; 2015: 905215. 
11. Arumugam M, Raes J, Pelletier E et al. Enterotypes of the human gut micro-biome. Nature 2011; 473 (7346): 174–80.
12. Tap J et al. Towards the human intestinal microbiota phylogenetic core. En-viron Microbiol 2009; 11 (10): 2574–84.
13. Rey FE et al. Dissecting the in vivo metabolic potential of two human gut acetogens. J Biol Chem 2010; 285 (29): 22082–90.
14. Vital M, Howe AC, Tiedje JM. Revealing the bacterial butyrate synthesis pathways by analyzing (meta)genomic data. MBio 2014; 5 (2): e00889.
15. Louis P, Flint HJ. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol Lett 2009; 294 (1): 1–8. 
16. Pozuelo M, Panda S, Santiago A et al. Reduction of butyrate- and methane-pro-ducing microorganisms in patients with Irritable Bowel Syndrome. Sci Rep 2015; 5: 12693. 
17. Nylund L, Nermes M, Isolauri E et al. Severity of atopic disease inversely corre-lates with intestinal microbiota diversity and butyrate-producing bacteria. Al-lergy 2015; 70 (2): 241–4. 
18. Le Chatelier E, Nielsen T, Qin J et al. Richness of human gut microbiome corre-lates with metabolic markers. Nature 2013; 500 (7464): 541–6. 
19. Ситкин С.И., Ткаченко Е.И., Вахитов Т.Я. Метаболический дисбиоз ки-шечника и его биомаркеры. Экспериментальная и клиническая га-строэнтерология. 2015; 124 (12): 6–29. 
[Sitkin S.I., Vakhitov T.Y. Metabolic dysbiosis of the gut microbiota and its biomarkers. Experimental and Clinical Gastroenterology. 2015; 124 (12): 6–29 (in Russian)].
20. Чиркин В.И., Ардатская М.Д., Лазарев И.А. Долгосрочные эффекты пре-парата пищевых волокон псиллиума (Мукофальк) у пациентов с мета-болическим синдромом. Клинические перспективы гастроэнтерологии, гепатологии. 2012; 1: 34–42. 
[Chirkin V.I., Lazarev I.A., Ardatskaya M.D. Long-term effects of alimentary fibers agent of psyllium (Mucofalk) in patients with metabolic syndrome. Clinicheskiye perspectivy gastroenterologii, gepatologii. 2012; 1: 34–42 (in Russian)].
21. Grasset E, Puel A, Charpentier J et al. A specific gut microbiota dysbiosis of type 2 diabetic mice induces GLP-1 resistance through an enteric NO-dependent and gut-brain axis mechanism. Cell Metab 2017; 25 (5): 1075–90. 
22. Claus SP. Will gut microbiota help design the next generation of GLP-1-based therapies for type 2 diabetes? Cell Metab 2017; 26 (1): 6–7.
23. Delzenne NM, Cani PD, Everard A et al. Gut microorganisms as promising tar-gets for the management of type 2 diabetes. Diabetologia 2015; 58: 2206–17.
24. Olivares M, Schüppel V Hassan AM et al. The potential role of the dipeptidyl peptidase-4-like activity from the gut microbiota on the host health. Front Mi-crobiol 2018; 9: 1900.
25. Sikalidis AK, Maykish A. The Gut Microbiome and Type 2 Diabetes Mellitus: Dis-cussing a Complex Relationship. Biomedicines 2020; 8 (1): 8.
26. Petersen C, Round JL. Defining dysbiosis and its influence on host immunity and disease. Cell Microbiol 2014; 16: 1024–33.
27. Liou AP, Paziuk M, Luevano JM et al. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med 2013; 5: 178ra41.
28. Ding S, Chi MM, Scull BP et al. High-fat diet: Bacteria interactions promote in-testinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. PLoS ONE 2010; 5: e12191.
29. Saad MJA, Santos A, Prada PO. Linking gut microbiota and inflammation to obesity and insulin resistance. Physiology 2016; 31: 283–93.
30. Bouter K, van Raalte D, Groen A, Nieuwdorp M. Role of the Gut Microbiome in the Рathogenesis of Obesity and Obesity-Related Metabolic Dysfunction. Gas-troenterology 2017; 152: 1671–8. 
31. Hartstra AV, Bouter KE, Bäckhed F, Nieuwdorp M. Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes Care 2015; 38 (1): 159–65.
32. Ткач С.М., Дорофеева А.А. Соотношение основных филотипов кишечной микробиоты у больных сахарным диабетом 2-го типа. Клиническая эн-докринология и эндокринная хирургия. 2018; 3 (63): 7–14. 
[Tkach S., Dorofeeva A. The ratio of the main types of intestinal microbiota in patients with type 2 diabetes mellitus. Clinical endocrinology and endocrine surgery 2018; 3 (63): 7–14 (in Russian)].
33. Ураков А.Л., Гуревич К.Г., Сорокина Ю.А. и др. Взаимосвязь клинической эффективности сахароснижающих препаратов, микробиоты кишеч-ника, рациона питания и генотипа пациента при сахарном диабете 2-го типа. Обзоры по клинической фармакологии и лекарственной тера-пии. 2018; 16 (4): 11–8. 
[Urakov A.L., Gurevich K.G., Sorokina I.A. et al. Relationship of clinical efficacy of glucose lowering agents, gut microbiota, diet, and patient’s genotype in di-abetes mellitus type 2. Reviews on Clinical Pharmacology and Drug Therapy 2018; 16 (4): 11–8 (in Russian)]. 
34. Grasset E, Puel A, Charpentier J et al. A specific gut microbiota dysbiosis of type 2 diabetic mice induces glp-1 resistance through an enteric no-dependent and gut-brain axis mechanism. Cell Metab 2017; 26 (1): 278.
35. Ардатская М.Д., Гарушьян Г.В., Мойсак Р.П., Топчий Т.Б. Роль короткоце-почечных жирных кислот в оценке состояния микробиоценоза кишеч-ника и его коррекции у пациентов с НАЖБП различных стадий. Экспери-ментальная и клиническая гастроэнтерология. 2019; 161 (1): 106–16. [Ardatskaya M.D., Garushyan G.V., Moysak R P., Topchiy T.B. Role of short chain fatty acids in evaluation of gut microbiocenosis disorders and their correction in patients with NAFLD of different stages. Experimental and Clinical Gas-troenterology. 2019; 161 (1): 106–16 (in Russian)].
36. Курмангулов А.А., Дороднева Е.Ф., Исакова Д.Н. Функциональная актив-ность микробиоты кишечника при метаболическом синдроме. Ожире-ние и метаболизм. 2016; 13 (1): 16–9. 
[Kurmangulov A.A., Dorodneva E.F., Isakova D.N. Functional activity of intesti-nal microbiota with metabolic syndrome. Obesity and metabolism 2016; 13 (1): 16–9 (in Russian)].
37. Schwiertz A, Taras D, Schäfer K et al. Microbiota and SCFA in lean and over-weight healthy subjects. Obesity (Silver Spring) 2010; 18 (1): 190–5.
38. Napolitano A, Miller S, Nicholls AW et al. Novel gut-based pharmacology of metformin in patients with type 2 diabetes mellitus. PLoS One 2014; 9 (7): e100778.
39. De la Cuesta-Zuluaga J, Mueller NT, Corrales-Agudelo V et al. Metformin is as-sociated with higher relative abundance of mucin-degrading akkermansia muciniphila and several short-chain fatty acid-producing microbiota in the gut. Diabetes Care 2017; 40 (1): 54–62.
40. Burton JH, Johnson M, Johnson J et al. Addition of a gastrointestinal micro-biome modulator to metformin improves metformin tolerance and fasting glu-cose levels. J Diabetes Sci Technol 2015; 9 (4): 808–14.
41. Zhao L, Zhang F, Ding X et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 2018; 359 (6380): 1151–6.
42. Ардатская М.Д. Пробиотики, пребиотики и метабиотики в коррекции микроэкологических нарушений кишечника. Медицинский совет. 2015; 13: 94–9.
[Ardatskaya M.D. Probiotics, prebiotics and metabiotics in the treatement of microecological bowel disorders. Medical Council. 2015; 13: 94–9 (in Rus-sian)].
43. Rao TP, Hayakawa M, Minami T et al. Post-meal perceivable satiety and subse-quent energy intake with intake of partially hydrolysed guar gum. Br J Nutr 2015; 113: 1489–98.
44. Дедов И.И., Шестакова М.В., Майоров А.Ю. Алгоритмы специализирован-ной медицинской помощи больным сахарным диабетом. Сахарный диа-бет. 2019; 22 (S1): 1–144. 
[Dedov I.I., Shestakova M.V., Mayorov A.Y. Algorithms of specialized medical care for patients with diabetes mellitus. Diabetes mellitus. 2019; 22 (S1): 1–144 (in Russian)].
45. Черникова Н.А. Практические аспекты рационального питания при са-харном диабете. Русский медицинский журнал. 2009; 10: 702. 
[Chernikova N.A. Practical aspects of rational nutrition in diabetes mellitus. Russian Medical Journal 2009; 10: 702 (in Russian)].
46. Вербовой А.Ф., Шаронова Л.А., Косарева О.В. Принципы рационального питания пациентов с сахарным диабетом. Самара: СамГМУ, 2014. 
[Verbovoy A.F., Sharonova L.A., Kosareva O.V. Principles of rational nutrition of patients with diabetes mellitus. Samara: SamGMU, 2014 (in Russian)].
47. Rao TP, Quartarone G. Role of guar fiber in improving digestive health and function. Nutrition 2019; 59: 158–69. 
48. Ustundag, G, Kuloglu Z, Kirbas N, Kansu A. Can partially hydrolyzed guar gum be an alternative to lactulose in treatment of childhood constipation? Turk J Gastroenterol 2010; 21 (4): 360.
49. Slavin J. Fiber and Prebiotics: Mechanisms and Health Benefits. Nutrients 2013; 5: 1417–35. 
50. Yasukawa Z, Inoue R, Ozeki M, Okubo T et al. Effect of Repeated Consumption of Partially Hydrolyzed Guar Gum on Fecal Characteristics and Gut Micro-biota: A Randomized, Double-Blind, Placebo-Controlled, and Parallel-Group Clinical Trial. Nutrients 2019; 11 (9): 2170.
51. Pinoue R, Sakaue Y, Kawada Y et al. Dietary supplementation with partially hy-drolyzed guar gum helps improve constipation and gut dysbiosis symptoms and behavioral irritability in children with autism spectrum disorder. J Clin Biochem Nutr 2019; 64 (3): 217–23.
52. Kapoor MP et al. Impact of partially hydrolyzed guar gum (PHGG) on consti-pation prevention: a systematic review and meta-analysis. J Func Foods 2017; 33: 52–66.
53. Takahashi H et al. Influence of partially hydrolyzed guar gum on constipation in women.  J Nutr Sci Vitaminol 1994; 40 (3): 251–9.
54. Okubo T et al. Effects of Partially Hydrolyzed Guar Gum Intake on Human In-testinal Microflora and Its Metabolism. Biosci Biotech Biochem 1994; 58 (8): 1364–9.
55. Mudgil D, Barak S, Patel A, Shah N. Partially hydrolyzed guar gum as a poten-tial prebiotic source. Int J Biol Macromol 2018; 112: 207–10. 
56. Takayama S, Katada K, Takagi T et al. Partially hydrolyzed guar gum attenu-ates non-alcoholic fatty liver disease in mice through the gut-liver axis. World J Gastroenterol 2021; 27 (18): 2160–76.
57. Ohashi Y, Sumitani K, Tokunaga M et al. Consumption of partially hydrol-ysed guar gum stimulates Bifidobacteria and butyrate-producing bacteria in the human large intestine. Benef Microbes 2015; 6 (4): 451–5.
58. Velázquez M, Davies C, Marett R et al. Effect of Oligosaccharides and Fibre Substitutes on Short-chain Fatty Acid Production by Human Faecal Mi-croflora. Anaerobe 2000; 6: 87–92.
59. Ek AC, Larsson J, von Schenck H. The correlation between energy, malnutri-tion and clinical outcome in an elderly hospital population. Clin Nutr 1990; 9: 185–9.
60. Golay A, Schneider H, Bloese D et al. The effect of a liquid supplement con-taining guar gum and fructose on glucose tolerance in non-insulin-depen-dent diabetic patients. Nutr Metab Cardiovasc Dis 1995; 5: 141–8.
61. Yamatoya K, Dekiya K, Yamada H, Ichikawa T. Effects of partially hy-drolyzed guar gum on postprandial plasma glucose and lipid levels in hu-mans. J Jpn Soc Nutr FoodSci 1993; 46: 199–203.
62. Tsuda K, Inden T, Yamanaka K, Ikeda Y. Effect of partially hydrolyzed guar gum on elevation of blood glucose after sugar Intake In human volunteers. Jpn J Diet Fib 1998; 2: 1522.
63. Yoon S-J, Chu D-C, Raj L. Chemical and Physical Properties, Safety and Appli-cation of Partially Hydrolized Guar Gum as Dietary Fiber. J Clin Biochem Nutr 2008; 42: 1–7.
64. Dall'Alba V, Silva F, Antonio J, Steemburgo T et al. Improvement of the metabolic syndrome profile by soluble fibre – guar gum – in patients with type 2 diabetes: A randomised clinical trial. British J Nutrition 2013; 110 (9): 1601–10.
65. Trinidad T, Perez E et al. Glycemic index of Sunfibre (Cyamoposis tetragonolobus) products in normal and diabetic subjects. Int J Food Sci Technol 2004; 39: 1093–8.