Метаболический синдром и кишечная микробиота


Л.В. Егшатян (1), А.М. Мкртумян (1), Л.А. Звенигородская (2)

(1) Кафедра эндокринологии и диабетологии ГБОУ ВПО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава РФ, Москва; (2) ГБУЗ «Московский клинический научный центр» МЗ ДЗМ, Москва
В статье представлен обзор современной литературы, обобщающий экспериментальные и клинические данные о роли микробиоты кишечника и ее изменениях, ассоциированных с метаболическим синдромом. Микробиота – это своеобразный индикатор состояния макроорганизма, реагирующая на возрастные, физиологические, диетические, климато-географические факторы изменением качественного и количественного состава. Все эти изменения влияют на развитие хронического системного воспаления, метаболических нарушений. Очевидно, что поддержание гомеостаза и нормального обмена веществ невозможно без восстановления разнообразия микроорганизмов кишечника.

Литература


1. Kaur J. A comprehensive review on metabolic syndrome. Cardiol. Res. Pract. 2014;943162.

2. International Diabetes Federation. The IDF consensus worldwide definition of the metabolic syndrome. Available from: URL: http://www.idf.org/webdata/docs/MetSyndrome_FINAL.pdf.

3. Wild S.H., Byrne C.D. (eds).The global burden of the metabolic syndrome and its consequences for diabetes and cardiovascular disease. The metabolic syndrome. 2005. P. 1–43.

4. Weiss R., Dziura J., Burgert T.S., Tamborlane W.V., Taksali S.E., Yeckel C.W., Allen K., Lopes M., Savoye M., Morrison J., Sherwin R.S., Caprio S. Obesity and the metabolic syndrome in children and adolescents. N. Engl. J. Med. 2004;350:2362–74.

5. The Human Microbiome Project Consortium Structure, function and diversity of the healthy human microbiome. Nature. 2012;486:207–14.

6. Guarner F., Malagelada J.R. Gut flora in health and disease. Lancet. 2003;361:512–19.

7. Mazmanian S.K., Liu C.H., Tzianabos A.O., Kasper D.L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005;122:107–18.

8. Backhed F., Ding H., Wang T., Hooper L.V., Koh G.Y., Nagy A., Semenkovich C.F., Gordon J.I. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA. 2004;101:15718–23.

9. Ley R.E. Obesity and the human microbiome. Curr. Opin. Gastroenterol. 2010;26(1):5–11.

10. Qin J., Li Y., Cai Z., et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490:55–60.

11. Everard A.I., Cani P.D. Diabetes, obesity and gut microbiota. Best. Pract. Res. Clin. Gastroenterol. 2013;27(1):73–83.

12. Mai V., Colbert L.H., Perkins S.N., Schatzkin A., Hursting S.D. Intestinal microbiota: a potential diet-responsive prevention target in ApcMin mice. Mol. Carcinog. 2007;46:42–8.

13. Creely S.J., McTernan P.G., Kusminski C.M., et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am. J. Physiol. Endocrinol. Metab. 2007;292:E740–47.

14. Clarke S.F., Murphy E.F., Nilaweera K., Ross P.R., Shanahan F., O’Toole P.W., Cotter P.D. The gut microbiota and its relationship to diet and obesity: new insights. Gut. Microbes. 2012;3:186–202.

15. Cani P.D., Amar J., Iglesias M.A., Poggi M., Knauf C., Bastelica D., Neyrinck A.M., Fava F., Tuohy K.M., Chabo C., Waget A., Delmée E., Cousin B., Sulpice T., Chamontin B., Ferrières J., Tanti J.F., Gibson G.R., Casteilla L., Delzenne N.M., Alessi M.C., Burcelin R. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761–72.

16. Fitzgerald K.A., Rowe D.C., Golenbock D.T. Endotoxin recognition and signal transduction by the TLR4/MD2-complex. Microbes. Infect. 2004;6:1361–67.

17. Lee J.Y., Hwang D.H. The modulation of inflammatory gene expression by lipids: mediation through Toll-like receptors. Molecules and Cells. 2006;21(2):174–85.

18. Gangloff S., Hijiya N., Haziot A., Goyert S.M. Lipopolysaccharide structure influences the macrophage response via CD14-independent and CD14-dependent pathways. Clin. Inf. Dis. 1999;28:491–96.

19. Biagi B., Nylund L., Candela M., Ostan R., Bucci L., Pini E., Nikkïla J., Monti D., Satokari R., Franceschi C., Brigidi P., De Vos W. Through ageing, and beyond: Gut microbiota and inflammatory status in seniors and centenarians. PLoS One. 2010;5:10667.

20. Sokol H., Pigneur B., Watterlot L., et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. PNAS. 2008;105:16731–36.

21. Физиология человека / Под ред. В.М. Покровского, Г.Ф. Коротько. 2003. 656 с.

22. Cavalcante-Silva L.H.A., Galvão J.G.F.M., da Silva J.S., de Sales-Neto J.M., Rodrigues-Mascarenhas S. Obesity-Driven Gut Microbiota Inflammatory Pathways to Metabolic Syndrome. Front. Physiol. 2015;6:341.

23. Thjodleifsson B., Olafsson I., Gislason D., Gislason T., Jögi R., Janson C. Infections and obesity: A multinational epidemiological study. Scand. J. Infect. 2008;40:381–86.

24. Backhed F., Ding H., Wang T., Hooper L.V., Koh G.Y., Nagy A., Semenkovich C.F., Gordon J.I. The gut microbiota as an environmental factor that regulates fat storage. PNAS. 2004;101:15718–23.

25. Qin J., Li Y., Cai. Z., et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490(7418):55–60.

26. Karlsson F., Tremaroli V., Nookaew I., Bergström G., Behre C.J., Fagerberg B., Nielsen J., Bäckhed F. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature. 2013;498:99–103.

27. Pussinen P.J., Havilinna A.S., Lehto M., Sundvall J., Salomaa V. Endotoxemia is associated with an increased risk of incident diabetes. Diabetes. Care. 2011;34(2):392–97.

28. Ley R.E., Turnbaugh P.J., Klein S., Gordon J.I. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444:1022–23.

29. Turnbaugh P., Ley R., Mahowald M., Magrini V., Mardis E.R., Gordon J.I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–31.

30. Amar J., Chabo C., Waget A., et al. Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment. EMBO. Mol. Med. 2011;3(9):559–72.

31. Amar J., Setino M., Lange C., Chabo C., Iacovoni J., Mondot S., Lepage P., Klopp C., Mariette J., Bouchez O., Perez L., Courtney M., Marre M., Klopp P., Lantieri O., Doré J., Charles M., Balkau B., Burcelin R. Involvement of tissue bacteria in the onset of diabetes in humans: evidence for a concept. Diabetologia. 2011;54(12)6:3055–61.

32. Belzer C., de Vos W.M. Microbes inside-from diversity to function: The case of Akkermansia. ISME. J. 2012;6(8):1449–58.

33. Cani P.D., Possemiers S., Van de Miele T., Guiot Y., Everard A., Rottier O., Geurts L., Naslain D., Neyrinck A., Lambert D.M., Muccioli G.G., Delzenne N.M. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut. 2009;58(8):1091–103.

34. Murphy E.F., Cotter P.D., Healy S., Marques T.M., O’Sullivan O., Fouhy F., Clarke S.F., O’Toole P.W., Quigley E.M., Stanton C., Ross P.R., O’Doherty R.M., Shanahan F. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut. 2010;59(12):1635–42.

35. Everard A., Belzer C., Geurts L., et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci. USA. 2013;110:9066–71.

36. Ley R.E., Turnbaugh P., Klein S., Gordon J.I. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444:1022–23.

37. Turnbaugh P.J., Hamady M., Yatsunenko T., Cantarel B.L., Duncan A., Ley R.E., Sogin M.L., Jones W.J., Roe B.A., Affourtit J.P., Egholm M., Henrissat B., Heath A.C., Knight R., Gordon J.I. A core gut microbiome in obese and lean twins. Nature. 2009;457:480–84.

38. Zhang H., DiBaise J.K., Zuccolo A., Kudrna D., Braidotti M., Yu Y., Parameswaran P., Crowell M.D., Wing R., Rittmann B.E., Krajmalnik-Brown R. Human gut microbiota in obesity and after gastric bypass. Proc. Natl. Acad. Sci. USA. 2009;106(7):2365–70.

39. Schwiertz A., Taras D., Schafer K., Beijer S., Bos N.A., Donus C., Hardt P.D. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring). 2010;18(1):190–95.

40. Jumpertz R., Le D.S., Turnbaugh P.J., Trinidad C., Bogardus C., Gordon J.I., Krakoff J. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am. J. Clin. Nutr. 2011;94(1):58–65.

41. Tims S., Derom C., Jonkers D.M., Vlietinck R., Saris W.H., Kleerebezem M., de Vos W.M., Zoetendal E.G. Microbiota conservation and BMI signatures in adult monozygotic twins. ISME. J. 2013;7:707–17.

42. Escobar J.S., Klotz B., Valdes B.E., Agudelo G.M. The gut microbiota of Colombians differs from that of Americans, Europeans and Asians. BMC. Microbiol. 2014;14:311.

43. Deopurkar R., Granim H., Friedman J., Abuaysheh S., Sia C.L., Mohanty P., Viswanathan P., Chaudhuri A., Dandona P. Differential effects of cream, glucose, and orange juice on inflammation, endotoxin, and the expression of Toll-like receptor-4 and suppressor of cytokine signaling-3. Diabetes. Care. 2010;33(5):991–97.

44. Koeth R.A., Wang Z., Levison B.S., Buffa J.A., Org E., Sheehy B.T., Britt E.B., Fu X., Wu Y., Li L., Smith J.D., DiDonato J.A., Chen J., Li H., Wu G.D., Lewis J.D., Warrier M., Brown J.M., Krauss R.M., Tang W.H., Bushman F.D., Lusis A.J., Hazen S.L. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 2013;19:576–85.

45. Rebouche C., Mack D., Edmonson P. L-Carnitine dissimilation in the gastrointestinal tract of the rat. Biochemistry. 1984;23:6422–26.

46. Zeisel S., Mar M., Howe J., Holden J.M. Concentrations of choline-containing compounds and betaine in common foods. J. Nutr. 2003;133:1302–307.

47. Demarquoy J., Georges B., Rigault C., et al. Radioisotopic determination of L-carnitine content in foods commonly eaten in western countries. Food. Chem. 2004;86:137–42.

48. Estruch R., Ros E., Salas-Salvadо J., Covas M.I., Corella D., Arós F., Gómez-Gracia E., Ruiz-Gutiérrez V., Fiol M., Lapetra J., Lamuela-Raventos R.M., Serra-Majem L., Pintó X., Basora J., Muñoz M.A., Sorlí J.V., Martínez J.A., Martínez-González M.A. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. N. Engl. J. Med. 2013;368(14):1279–90.

49. Wu G.D., Chen J., Hoffmann C., Bittinger K., Chen Y.Y., Keilbaugh S.A., Bewtra M., Knights D., Walters W.A., Knight R., Sinha R., Gilroy E., Gupta K., Baldassano R., Nessel L., Li H., Bushman F.D., Lewis J.D. Linking long-term dietary patterns with gut microbial enterotypes. Science (New York). 2011;334:105–8.

50. Duncan S.H., Lobley G.E., Holtrop G., Knauf C., Burcelin R.G., Tuohy K.M., Gibson G.R., Delzenne N.M. Human colonic microbiota associated with diet, obesity and weight loss. Int. J. Obes. (Lond.). 2008;32(11):1720–24.

51. Jeffery I.B., O’Toole P.W. Diet-microbiota interactions and their implications for healthy living. Nutrients. 2013;5(1):234–52.

52. Cani P.D., Neyrinck A.M., Fava F., Knauf C., Burcelin R.G., Tuohy K.M., Gibson G.R., Delzenne N.M. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007;50(11):2374–83.

53. Muccioli G.G., Naslain D., Backhed F., Reigstad C.S., Lambert D.M., Delzenne N.M., Cani P.D. The endocannabinoid system links gut microbiota to adipogenesis. Mol. Syst. Biol. 2010;6:392.

54. Everarda A., Belzerb C., Geurtsa L. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. PNAS. 2013;110(22):9069.

55. Liou A.P., Paziuk M., Luevano J.M. Jr, Machineni S., Turnbaugh P.J., Kaplan L.M. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci. Transl. Med. 2013;5(178):178ra41.

56. Shin N.R., Lee J.C., Lee H.Y., et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 2013;63:727–35.

57. Lee H., Ko G. Effect of Metformin on Metabolic Improvement and Gut Microbiota. App. Environ. Microbiol. 2014;80(19):5935–43.

58. Hur K.Y., Lee M.S. New mechanisms of metformin action: Focusing on mitochondria and the gut. J. Diabetes Investig. 2015;6(6):600–9.


Об авторах / Для корреспонденции


А.М. Мкртумян – д.м.н., проф., заслуженный врач РФ, рук. эндокринологической службы ГБУЗ МКНЦ ДЗ г. Москвы, зав. кафедрой эндокринологии и диабетологии ГБОУ ВПО МГМСУ им. А.И. Евдокимова Минздрава РФ, Москва; 8 (495) 688-97-82


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