E.Yu. Plotnikova (1), O.A. Krasnov (2, 3)

(1) Department of training of primary care physician SBEI HPE KemSMA of RMPH, Kemerovo; (2) Department of Hospital Surgery SBEI HPE KemSMA of RMPH, Kemerovo; (3) MBHCI CCH №3 n.a. Podgorbunsky, Kemerovo
The article highlights the problem of the relationship of the human intestinal microbiome with metabolic syndrome. Changes in intestinal bacterial proportions in obese people have attracted the attention of scientists around the world, especially in relation to their impact on the metabolism. Increase proportion of Firmicutes and Actinobacteria and reducing proportion of Bacteroidetes are associated with increased serum lipopolysaccharide levels, insulin resistance, weight gain and other comorbid manifestations of metabolic syndrome. Underlying mechanisms of this interdisciplinary problems are actively evaluated to optimize the prevention and treatment of obesity and type 2 diabetes mellitus.


  1. Alcock J., Maley C.C., Aktipis C.A. Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms. BioEssays. 2014;36(10):940–49.
  2. Lyte M. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. BioEssays. 2011;33:574–81.
  3. Baraldi M., Avallone R., Corsi L., et al. Natural endogenous ligands for benzodiazepine receptors in hepatic encephalopathy. Metab Brain Dis. 2009;24:81–93.
  4. Clarke G., Stilling R.M., Kennedy P.J., Stanton C., Cryan J.F., Dinan T.G. Gut microbiota: the neglected endocrine organ. Mol. Endocrinolme. 2014;1:108.
  5. Eisenhofer G., Aneman A., Friberg P., Hooper D., Fandriks L, Lonroth H, Hunyady B, Mezey E. Substantial production of dopamine in the human gastrointestinal tract. J. Clin. Endocrinol. Metab. 1997; 82:3864–71.
  6. Kim D.Y., Camilleri M. Serotonin: a mediator of the brain-gut connection. Am. J. Gastroenterol. 2000;95:2698–709.
  7. Vague J. La diff, rentiation sexuelle, facteur d, terminant des formes de l’ob, sit. Presse Med. 1947; 30:339–40.
  8. Alberti K.G., Zimmet P.Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet. Med. 1998;15:539–53.
  9. Alberti K.G., Zimmet P., Shaw J. The metabolic syndrome–a new worldwide definition. Lancet. 2005;366:1059–62.
  10. Costello E.K., Lauber C.L., Hamady M., Fierer N., Gordon J.I., Knight R. Bacterial community variation in human body habitats across space and time. Science. 2009;326:1694–97.
  11. Backhed F., Ley R.E., Sonnenburg J.L., Peterson D.A., Gordon J.I. Host-bacterial mutualism in the human intestine. Science. 2005;307:1915–20.
  12. O’Hara A.M., Shanahan F. The gut flora as a forgotten organ. EMBO Rep. 2006;7:688–693.
  13. Qin J., Li R., Raes J., et al. Meta HIT Consortium. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59–65.
  14. Sommer F., Backhed F. The gut microbiota – masters of host development and physiology. Nat. Rev. Microbiol. 2013;11:227–38.
  15. Tremaroli V., Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489:242–49.
  16. Mackie R.I., Sghir A., Gaskins H.R. Developmental microbial ecology of the neonatal gastrointestinal tract. Am. J. Clin. Nutr. 1999;69:1035S–45S.
  17. published online ahead of print June 26, 2007
  18. Ley R.E., Turnbaugh P.J., Klein S., Gordon J.I. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444:10223.
  19. Ouwehand A., Isolauri E., Salminen S. The role of the intestinal microflora for the development of the immune system in early childhood. Eur. J. Nutr. 2002;41:132–37.
  20. Eckburg P.B., Bik E.M., Bernstein C.N., Purdom E., Dethlefsen L., Sargent M., Gill S.R., Nelson K.E., Relman D.A. Diversity of the human intestinal microbial flora. Science. 2005;308:1635–38.
  21. Zoetendal E.G., Akkermans A.D.L., Akkermans-van Vliet W.M., et al. The host genotype affects the bacterial community in the human gastrointestinal tract. Microb Ecol Health Dis. 2001; 13:129–34.
  22. Hopkins M.J., Sharp R., MacFarlane G.T. Age and disease related changes in intestinal bacterial populations assessed by cell culture, 16S rRNA abundance, and community cellular fatty acid profiles. Gut. 2001;48:198–205.
  23. Hill J.O. Understanding and addressing the epidemic of obesity: an energy balance perspective. Endocr. Rev. 2006;27:750–61.
  24. Wu X., Ma C., Han L., Nawaz M, Gao F., Zhang X., Yu P., Zhao C., Li L., Zhou A., Wang J., Moore J.E., Millar B.C., Xu J. Molecular characterisation of the faecal microbiota in patients with type II diabetes. Curr. Microbiol. 2010;61:69–78.
  25. 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 (SilverSpring). 2010;18:190–95.
  26. Furet J.P., Kong L.C., Tap J., Poitou C., Basdevant A., Bouillot J.L., Mariat D., Corthier G., Dore J., Henegar C., Rizkalla S., Clement K. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes. 2010;59:3049–57.
  27. O’Mahony D., Murphy S., Boileau T., Park J., et al. Bifidobacterium animalis AHC7 protects against pathogen-induced NF-kappaB activa-tion in vivo. BMC Immun. 2010;11:63.
  28. Kalliomaki M., Collado M.C., Salminen S., Iso-lauri E. Early differences in fecal microbiota composition in children may predict overweight. Am. J. Clin. Nutr. 2008;87:534–38.
  29. Vrieze A., Van Nood E., Holleman F., Salojarvi J., Kootte R.S., Bartelsman J.F., Dallinga-Thie G.M., Ackermans M.T., Serlie M.J., Oozeer R., Derrien M., Druesne A., Van Hylckama Vlieg J.E., Bloks V.W., Groen A.K., Heilig H.G., Zoetendal E.G., Stroes E.S., de Vos W.M., Hoekstra J.B., Nieuwdorp M. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012;143:913–16 e917.
  30. 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(44):15718–2310.
  31. Turnbaugh P.J., Ley R.E., Mahowald M.A., Magrini V., Mardis E.R., Gordon J.I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027–3110.1038.
  32. 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):58–6510.
  34. Ley R.E., Hamady M., Lozupone C., Turnbaugh P.J., Ramey R.R., Bircher J.S., Schlegel M.L., Tucker T.A., Schrenzel M.D., Knight R., Gordon J.I. Evolution of mammals and their gut microbes. Science. 2008;320:1647–51.
  35. Muegge B.D., Kuczynski J., Knights D., Cle-mente J.C., Gonzalez A., Fontana L., Henrissat B., Knight R., Gordon J.I. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science. 2011;332:970–74.
  36. 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.
  37. 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. 2011;334:105–08.
  38. Lin H.V., Frassetto A., Kowalik E.J., Nawrocki A.R., Lu M.M., Kosinski J.R., Hubert J.A., Szeto D., Yao X., Forrest G., Marsh D.J. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One. 2012;7(4):e35240.
  39. Shen J., Obin M.S., Zhao L. The gut microbiota, obesity and insulin resistance. Mol. Aspects Med. 2013;34(1):39–5810.
  40. Samuel B.S., Gordon J.I. A humanized gnotobiotic mouse model of host-archaeal-bacterial mutualism. Proc. Natl. Acad. Sci. USA 2006;103(26):10011–610.
  41. Conterno L., Fava F., Viola R., Tuohy K.M. Obesity and the gut microbiota: does up-regulating colonic fermentation protect against obesity and metabolic disease? Genes Nutr. 2011;6(3):241–6010.
  42. Backhed F., Manchester J.K., Semenkovich C.F., Gordon J.I. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc. Natl. Acad. Sci. USA 2007;104(3):979–8410.
  43. Winder W.W., Hardie D.G. AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am. J. Physiol. 1999;277(1):E1–10.
  44. Field B.C., Wren A.M., Peters V., Baynes K.C., Martin N.M., Patterson M., Alsaraf S., Amber V,. Wynne K., Ghatei M.A., Bloom S.R. PYY3-36 and oxyntomodulin can be additive in their effect on food intake in overweight and obese humans. Diabetes. 2010;59(7):1635–910.
  45. Page A.J., Symonds E., Peiris M., Blackshaw L.A., Young R.L. Peripheral neural targets in obesity. Br. J. Pharmacol. 2012;166(5):1537–5810.
  46. Karra E., Chandarana K., Batterham R.L. The role of peptide YY in appetite regulation and obesity. J. Physiol. 2009;587(Pt 1):19–2510.
  47. Darzi J., Frost G.S., Robertson M. Do SCFA have a role in appetite regulation? Proc. Nutr. Soc. 2011;70(1):119–2810.
  48. Cuche G., Cuber J.C., Malbert C.H. Ileal short-chain fatty acids inhibit gastric motility by a humoral pathway. Am. J. Physiol. Gastrointest. Liver Physiol. 2000;279(5):G925–30.
  49. Bjursell M., Admyre T., Göransson M., Marley A.E., Smith D.M., Oscarsson J., Bohlooly-Y.M. Improved glucose control and reduced body fat mass in free fatty acid receptor 2-deficient mice fed a high-fat diet. Am. J. Physiol. Endocrinol. Metab. 2011;300(1):E211–2010.
  50. Samuel B.S., Shaito A., Motoike T., Rey F.E., Backhed F., Manchester J.K., Hammer R.E., Williams S.C., Crowley J., Yanagisawa M., Gordon J.I. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc. Natl. Acad. Sci. USA 2008;105(43):16767–7210.
  51. Dasu M.R., Ramirez S., Isseroff R.R. Toll-like receptors and diabetes: a therapeutic perspective. Clin. Sci. 2012;122(5):203–1410.
  52. Hayashi F., Smith K.D., Ozinsky A., Hawn T.R., Yi E.C., Goodlett D.R., Eng J.K., Akira S., Underhill D.M., Aderem A. The innate immune response to bacterial flagellin is mediated by toll-like receptor-5. Nature 2001;410(6832):1099–10310.
  53. Rhee S.H. Basic and translational understandings of microbial recognition by toll-like receptors in the intestine. J Neurogastroenterol Motil 2011; 17(1):28–3410.
  54. Vijay-Kumar M., Aitken J.D., Carvalho F.A., Cullender T.C., Mwangi S., Srinivasan S., Sitaraman S.V., Knight R., Ley R.E., Gewirtz A.T. Metabolic syndrome and altered gut microbiota in mice lacking toll-like receptor 5. Science. 2010;328(5975):228–3110.
  55. Shi H., Kokoeva M.V., Inouye K., Tzameli I., Yin H., Flier J.S. TLR4 links innate immunity and fatty acid–induced insulin resistance. J. Clin. Invest. 2006;116:3015–25.
  56. Caricilli A.M., Picardi P.K., de Abreu L.L., Ueno M., Prada P.O., Ropelle E.R., Hirabara S.M., Castoldi A., Vieira P., Camara N.O., Curi R., Carvalheira J.B., Saad M.J. Gut microbiota is a key modulator of insulin resistance in TLR 2 knockout mice. PLoS Biol. 2011;9:e1001212.
  57. Devaraj S., Tobias P., Kasinath B.S., Ramsamooj R., Afify A., Jialal I. Knockout of toll-like receptor-2 attenuates both the proinflammatory state of diabetes and incipient diabetic nephropathy. Arterioscler. Thromb. Vasc. Biol. 2011;31:1796–804.
  58. Schinner S., Scherbaum W.A., Bornstein S.R., Barthel A. Molecular mechanisms of insulin resistance. Diabet. Med. 2005; 22:674–82.
  59. Ozcan U., Cao Q., Yilmaz E., Lee A.H., Iwakoshi N.N., Ozdelen E., Tuncman G., Görgün C., Glimcher LH., Hotamisligil G.S. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 2004;306:457–61.
  60. Jagannathan-Bogdan M., McDonnell M.E., Shin H., Rehman Q., Hasturk H., Apovian C.M., Nikolajczyk B.S. Elevated proinflammatory cytokine production by a skewed T cell compartment requires monocytes and promotes inflammation in type 2 diabetes. J. Immunol. 2011;186:1162–72.
  61. Monroy A., Kamath S., Chavez A.O., et al. Impaired regulation of the TNF-β converting enzyme/tissue inhibitor of metalloproteinase 3 proteolytic system in skeletal muscle of obese type 2 diabetic patients: A new mechanism of insulin resistance in humans. Diabetologia. 2009;52:2169–81.
  62. Senn J.J., Klover P.J., Nowak I.A., Zimmers T.A., Koniaris L.G., Furlanetto R.W., Mooney R.A. Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J. Biol. Chem. 2003;278:13740–46.
  63. 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., Delmee E., Cousin B., Sulpice T., Chamontin B., Ferrieres 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.
  64. Cani P.D., Bibiloni R., Knauf C., Waget A., Neyrinck A.M., Delzenne N.M., Burcelin R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57:1470–81.
  65. Hornef M.W., Frisan T., Vandewalle A., Normark S., Richter-Dahlfors A. Toll-like receptor 4 resides in the golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells. J. Exp. Med. 2002;195:559–70.
  66. Hamedani A., Akhavan T., Samra R.A., Ander-son G.H. Reduced energy intake at breakfast is not compensated for at lunch if a high-insoluble-fiber cereal replaces a low-fiber cereal. Am. J. Clin. Nutr. 2009;89:1343–49.
  67. Weickert M.O., Roden M., Isken F., , Hoffmann D., Nowotny P., Osterhoff M., Blaut M., Alpert C., Gögebakan O., Bumke-Vogt C., Mueller F., Machann J., Barber T.M., Petzke K.J., Hierholzer J., Hornemann S., Kruse M., Illner A.K., Kohl A., Loeffelholz C.V., Arafat A.M., Möhlig M., Pfeiffer A.F. Effects of supplemented isoenergetic diets differing in cereal fiber and protein content on insulin sensitivity in overweight humans. Am. J. Clin. Nutr. 2011;94:459–71.
  68. Weickert M.O., Arafat A.M., Blaut M., Alpert C., Becker N., Leupelt V., Rudovich N., Möhlig M., Pfeiffer A.F. Changes in dominant groups of the gut microbiota do not explain cereal-fiber induced improvement of whole-body insulin sensitivity. Nutr. Metab. 2011;8:90.
  69. Isken F., Klaus S., Osterhoff M., Pfeiffer A.F., Weickert M.O. Effects of long-term soluble vs. insoluble dietary fiber intake on high-fat diet-induced obesity in C57BL/6J mice. J. Nutr. Biochem. 2010;21:278–84.
  70. Korner J., Leibe R.I. To eat or not to eat–how the gut talks to the brain. N. Engl. J. Med. 2003;349:926–28.
  71. Плотникова Е.Ю., Борщ М.В., Краснова М.В., Баранова Е.Н. Некоторые аспекты диагностики и лечения избыточной бактериальной контаминации тонкой кишки в клинической практике. Лечащий врач. 2013;2:52–6.
  72. Scarpellini E., Gabrielli M., Lauritano C.E., Lupascu A., Merra G., Cammarota G., Cazzato I.A., Gasbarrini G., Gasbarrini A. High dosage rifaximin for the treatment of small intestinal bacterial overgrowth. Aliment Pharmacol. Ther. 2007;25(7):781–86.
  73. Membrez M., Blancher F., Jaquet M., Bibiloni R., Cani P.D., Burcelin R.G., Corthesy I., Mace K., Chou C.J. Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice. FASEB. 2008;22:2416–26.
  74. 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;50:2374–83.
  75. Parnell J.A., Reimer R.A. Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am. J. Clin. Nutr. 2009;89:1751–59.
  76. Nilsson A.C., Ostman E.M., Holst J.J., Björck I.M. Including indigestible carbohydrates in the evening meal of healthy subjects improves glucose tolerance, lowers inflammatory markers, and increases satiety after a subsequent standardized breakfast. J. Nutr. 2008;138:732–39.
  77. Solga S.F., Buckley G., Clark J.M., Horska A., Diehl A.M. The effect of a probiotic on hepatic steatosis. J. Clin. Gastroenterol. 2008;42:1117–19.
  79. Kadooka Y., Sato M., Imaizumi K., Ogawa A., Ikuyama K., Akai Y., Okano M., Kagoshima M., Tsuchida T. Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. Eur. J. Clin. Nutr. 2010;64:636–43.
  80. Kadooka Y., Ogawa A., Ikuyama K., et al. The probiotic Lactobacillus gasseri SBT2055 inhibits enlargement of visceral adipocytes and upregulation of serum soluble adhesion molecule (sICAM-1) in rats. Int. Dairy J. 2011;30:1–5.
  81. Lee H.Y., Park J.H., Seok S.H., Baek M.W., Kim D.J., Lee K.E., Paek K.S., Lee Y., Park J.H. Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice. Biochim. Biophys Acta. 2006;1761:736–44.
  82. Rastmaneh R. High polyphenol, low probiotic diet for weight loss because of intestinal microbiota interaction. Chem. Biol. Interact. 2011;189:1–8.
  83. Mallappa R.H., Rokana N., Duary R.K., Panwar H., Batish V.K., Grover S. Management of metabolic syndrome through probiotic and prebiotic interventions. Indian J. Endocrinol. Metab. 2012;16(1):20–7.
  84. Saavedra J.M. Clinical applications ofprobiotic agents. Am. J. Clin. Nutr. 2001;73(6):1147–51.
  85. Bezkorovainy A. Probiotics: determinants of survival and growth in the gut. Am. J. Clin. Nutr. 2001;73(2):399–405.
  86. Madsen K.I. The use ofprobiotics in gastrointestinal disease. Can. J. Gastroenterol. 2001;15(12):817–22.
  87. Land M.H., Rouster–Stevens K., Woods C.R., Cannon M.I., Cnota J., Shetty A.K. Sepsis Associated With Probiotic Therapy Lactobacillus. Pediatrics. 2005;115:178–81.

About the Autors

E.Yu. Plotnikova - MD, Prof. at the Department of training of primary care physician, Head of the Course of Clinical Gastroenterology SBEI HPE KemSMA of RMPH
O.A. Krasnov – MD, Prof. at the Department of Hospital Surgery SBEI HPE KemSMA of RMPH, Chief Physician of the MBHCI CCH №3 n.a. Podgorbunsky, Kemerovo

Similar Articles

Бионика Медиа