Статья
ОЖИРЕНИЕ И МЕТАБОЛИЧЕСКИЙ СИНДРОМ: ПАТОФИЗИОЛОГИЧЕСКАЯ РОЛЬ КИШЕЧНОЙ МИКРОБИОТЫ И ПОТЕНЦИАЛЬНЫЕ ВОЗМОЖНОСТИ АЛЬТЕРНАТИВНОЙ ТЕРАПИИ
В обзоре представлены данные, характеризующие современное состояние знаний о связи между кишечной микробиотой, ожирением и метаболическим синдромом. Обсуждается патофизиологическая роль кишечной микробиоты в развитии ожирения и метаболического синдрома. Рассматриваются потенциальные возможности альтернативной терапии для контроля потребления энергии и снижения распространённости ожирения и метаболического синдрома.
1. Overweight & Obesity.. Centers for Disease Control and Prevention Available from: http://www.cdc.gov/obesity/data/adult.htm.
2. World Health Organization (WHO). Obesity and overweight. January 2015. Available from: http://www.who.int/mediacentre/factsheets/fs311/en/. Accessed 2 April 2016.
3. Alberti K.G., Zimmet P., Shaw J. The metabolic syndrome – a new worldwide definition. Lancet. 2005; 366: 1059-1062.doi:10.1016/S0140-6736(05)67402-8.
4. Despres J.P., Lemieux I., Bergeron J., Pibarot P., Mathieu P., Larose E. et al. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler.Thromb. Vasc. Biol. 2008; 28:1039-1049.doi:10.1161/ATVBAHA.107.159228.
5. Ramezani A., Raj D.S. The Gut Microbiome, Kidney Disease, and Targeted Interventions. J. Am. Soc. Nephrol. 2014; 25: 657-670.
6. Gill S.R., Pop M., Deboy R.T., Eckburg P.B., Turnbaugh P.J., Samuel B.S. et al. Metagenomic analysis of the human distal gut microbiome. Science. 2006; 312 (5778):1355-1359.
7. Steer T., Carpenter H., Tuohy K., Gibson G.R. Perspectives on the role of the human gut microbiota and its modulation by pro- and prebiotics. Nutr. Res. Rev. 2000; 13:229-254. doi: 10.1079/095442200108729089.
8. O’Hara A.M., Shanahan F. The gut flora as a forgotten organ. EMBO Rep. 2006; 7:688-693.
9. Nazli A., Yang P.C., Jury J., Howe K., Watson J.L.,Soderholm J.D. et al. Epithelia under metabolic stress perceive commensal bacteria as a threat. Am. J. Pathol. 2004;164:947–957.
10. Perry R.J., Samuel V.T., Petersen K.F., Shulman G.I. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes .Nature.2014;510:84–91.doi:10.1038/nature13478.
11. Saltiel A.R., Kahn C.R. Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 2001;414:799–806.doi:10.1038/414799a.
12. Gregor M.F., Hotamisligil G.S. Inflammatory mechanisms in obesity. Annu. Rev.Immunol. 2011; 29:415–445. doi:10.1146/annurevimmunol-031210-101322.
13. Cani P.D., Amar J., Iglesias M.A., Poggi M., Knauf C., Bastelica D. et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007; 56:1761–1772. doi:10.2337/db06-1491.
14. Cai D., Yuan M., Frantz D.F., Melendez P.A., Hansen L., Lee J. et al. Local and systemic insulin resistance resulting from hepatic activation of IKKbeta and NF-kappaB. Nat Med. 2005;11:183–190. doi:10.1038/nm1166.
15. Sell H., Habich C., Eckel J. Adaptive immunity in obesity and insulin resistance. Nat Rev Endocrinol.2012; 8:709–716. doi:10.1038/nrendo.2012.114.
16. Lumeng C.N., Saltiel A.R. Inflammatory links between obesity and metabolic disease. J Clin Invest. 2011;121:2111–2117. doi:10.1172/JCI57132.
17. Turnbaugh P.J., Ley R.E., Mahowald M.A., Magrini V., Mardis E.R., Gordon J.I. An obesityassociated gut microbiome with increased capacity for energy harvest. Nature. 2006; 444:1027-1031. doi:10.1038/nature05414.
18. Piya M.K., McTernan P.G., Kumar S. Adipokine inflammation and insulin resistence: the role of glucose, lipids and endotoxin. J. Endocrinol. 2013; 216:11-15.doi:10.1530/JOE-12-0498.
19. Backhed F., Ding H., Wang T., Hooper L.V., Koh G.Y., Nagy A. et al. The gut microbiota as an environmental factor regulates fat storage. Proc. Natl. Acad. Sci. USA. 2004; 101:15718-15723. doi:10.1073/pnas.0407076101.
20. Gibson G.R., Probert H.M., Loo J.V., Rastall R.A., Roberfroid M.B. Dietary modulation of the human colonic microbiota: updating the concept of prebiotics. Nutr.Res. Rev. 2004; 17:259-275. doi:10.1079/NRR200479.
21. Tremaroli V., Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012; 489: 242-249. doi: 10.1038/nature11552.
22. Musso G., Gambino R., Cassader M. Interactions between gut microbiota and host metabolism predisposing to obesity and diabetes. Annu.Rev. Med. 2011; 62:361-380.doi:10.1146/annurev-med-012510-175505.
23. Samuel B.S., Shaito A., Motoike T., Rey F.E., Backhed F., Manchester J.K. et al. 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. U.S.A. 2008; 105:16767-16772.doi:10.1073/pnas.0808567105.
24. Perry R.J., Peng L., Barry N.A., Cline G.W., Zhang D., Cardone R.L.et al. Acetate mediate a microbiome-brain-β-cell axis to promote metabolic syndrome. Nature. 2016; 534:213-217. doi: 10.1038/nature18309.
25. Ley R.E., Backhed F., Turnbaugh P., Lozupone C.A., Knight R.D., Gordon J.I. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. U.S.A. 2005; 102:11070-11075.doi:10.1073/pnas.0504978102.
26. Murphy E.F., Cotter P.D., Healy S., Marques T.M., O’Sullivan O., Fouhy F. et al. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut. 2010; 59:1635-1642.doi:10.1136/gut.2010.215665.
27. Ridaura V.K., Faith J.J., Rey F.E., Cheng J., Duncan A.E., Kau A.L. et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science.2013; 341:1241214.doi:10.1126/science.1241214.
28. Gregor M.F., Hotamisligil G.S. Inflammatory mechanisms in obesity. Annu. Rev. Immunol. 2011; 29:415-445.doi:10.1146/annurevimmunol-031210-101322.
29. Erridge C., Attina T., Spickett C.M., Webb D.J. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am. J. Clin. Nutr.2007;86:1286-1292.
30. Harte A.L., Varma M.C., Tripathi G., McGee K.C., Al-Daghri N.M., Al-Attas O.S. et al. High fat intake leads to acute postprandial exposure to circulating endotoxin in type 2 diabetic subjects. Diabetes Care. 2012; 35:375-382.doi:10.2337/dc11-1593.
31. Neal M.D., Leaphart C., Levy R., Prince J., Billiar T.R., Watkins S. et al. Enterocyte TLR4 mediates phagocytosis and translocation of bacteria across the intestinal barrier. J. Immunol. 2006;176: 3070-3079.
32. Cani P.D., Amar J., Iglesias M.A., Poggi M., Knauf C., Bastelica D. et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007; 56:1761-1762.doi:10.2337/db06-1491.
33. Neal M.D., Leafart C., Levy R., Prince J., Billiar T.R., Watkins S. et al. Enterocyte TLR4 mediates phagocytosis and translocation of bacteria across the intestinal barrier. J. Immunol. 2006; 176:3070-3079.
34. Vijay-Kumar M., Aitken J.D., Carvalho F.A., Cullender T.C., Mwangi S., Srinivasan S. et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science.2010; 328:228-231. doi:10.1126/science.1179721.
35. Tanty J.F., Ceppo F., Jager J., Berthou F. Implication of inflammatory signaling pathways in obesity-induced insulin resistence. Front. Endocrinol. (Lausanne). 2012; 3:181.doi:10.3389/fendo.2012.00181.
36. Ghoshal S., Witta J., ZhongJ., de Villiers W., Eckhardt E. Chylomicrons promote intestinal absorption of lipopolysaccharides. J. Lip. Res.2009; 50:90-97.doi:10.1194/jlr.M800156-JLR200.
37. Verges B., Duvillard L., Lagrost L.,Vachoux C., Garret C., Bouyer K. et al. Changes in lipoprotein kinetics associated with type 2 diabetes affect the distribution of lipopolycaccharides among lipoproteins. J. Clin. Endocrinol.Metab. 2014; 99:E1245-E1253. doi:10.1210/jc.2013-3463.
38. 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; 116:3015-3025.doi:10.1172/JCI28898.
39. Cani P.D., Bibiloni R., Knauf C.,Waget A., Neyrinck A.M., Delzenne N.M. et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008; 57:1470-1481. doi:10.2337/db07-1403.
40. Ghanim H., Abuaysheh S., Sia C.L., Korzeniewski K., Chaudhuri A., FernandezReal J.M. et al. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care.2009; 32:2281-2287.doi:10.2337/dc09-0979.
41. Russel W.R., Hoyles L., Flint H.J., Dumas M.E. Colonic bacterial metabolites and human health. Curr.Opin.Microbiol. 2013; 16:246-254. doi:10.1016/j.mib.2013.07.002.
42. DeMoss R.D., Moser K. Tryptophanase in diverse bacterial species. J. Bacteriol. 1969; 98:167-171.
43. Russel W.R., Duncan S.H., Scobbie L., Duncan G., Cantlay L., Calder A.G. et al. Major phenylpropanoid-derived metabolites in the human gut can arise from microbial fermentation of protein. Mol. Nutr..Food.Res. 2013; 57:523-535. doi:10.1002/mnfr.201200594.
44. Venkatesh M., Mukherjee S., Wang H., Li H., Sun K., Benechet A.P. et al. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity. 2014; 41:296–310. doi:10.1016/j.immuni.2014.06.014.
45. Ramadoss P., Marcus C., Perdew G.H. Role of the aryl hydrocarbon receptor in drug metabolism. Expert.Opin.Drug.Metab.Toxicol. 2005; 1: 9–21. doi:10.1517/17425255.1.1.9.
46. Cani P.D., Osto M., Geurts L., Everard A. Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes. 2012;3:279–288. doi:10.4161/gmic.19625.
47. Colman R.J., Rubin D.T. Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. J. Crohns. Colitis. 2014; 8:1569–1581. doi:10.1016/j.crohns.2014.08.006.
48. Vrieze A., Van Nood E., Holleman F., Salojarvi J., Kootte R.S., Bartelsman J.F. et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome.Gastroenterology. 2012; 143: 913–916. doi:10.1053/j.gastro.2012.06.031.
49. Kobyliak N., Conte C., Cammarota G., Haley A.P., Styriak I., Gaspar L. et al. Probiotics in prevention and treatment of obesity: a critical view. Nutr.Metab.(Lond). 2016;13:14.doi:10.1186/s12986-016-0067-0.
50. Hill C., Guarner F., Reid G., Gibson G.R., Merenstein D.J., Pot B. et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 2014;11:506–514. doi:10.1038/nrgastro.2014.66.
51. Delzenne N.M., Kok N. Effects of fructanstype prebiotics on lipid metabolism. Am. J. Clin. Nutr. 2001; 73 (2 Suppl):456S-458S.
52. Cani P.D., Neyrinck A.M., Fava F., Knauf C., Burcelin R.G., Tuohy K.M. et al. Selective increases of bifidobacteria in gut microflora improve high-fatdiet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007;50:2374–2383.doi:10.1007/s00125-007-0791-0.
53. van Hoffen E., Ruiter B., Faber J., M’Rabet L., Knol E.F., Stahl B. et al. A specific mixture of short-chain galacto-oligosaccharides and longchain fructo-oligosaccharides induces a beneficial immunoglobulin profile in infants at high risk for allergy. Allergy.2009; 64:484–487. doi:10.1111/j.1398-9995.2008.01765.x.
54. Cani P.D., Knauf C., Iglesias M.A., Drucker D.J., Delzenne N.M., Burcelin R. Improvement of glucose tolerance and hepatic insulin sensitivity by oligofructose requires a functional glucagon-like peptide 1 receptor. Diabetes. 2006; 55: 1484–1490.
55. Tazoe H., Otomo Y., Karaki S., Kato I., Fukami Y., Terasaki M. et al. Expression of shortchain fatty acid receptor GPR41 in the human colon. Biomed.Res. 2009; 30:149–156.
56. Zhou J., Hegsted M., McCutcheon K.L., Keenan M.J., Xi X., Raggio A.M. et al. Peptide YY and proglucagon mRNA expression patterns and regulation in the gut. Obesity (Silver Spring). 2006; 14: 683–689. doi:10.1038/oby.2006.77.
57. Delzenne N.M., Cani P.D., Neyrinck A.M. Modulation of glucagon-like peptide 1and energy metabolism by inulin and oligofructose: experimental data. J. Nutr. 2007; 137(11 Suppl): 2547S–2551S.
58. Garidou L., Pomie C., Klopp P., Waget A., Charpentier J., Aloulou M. et al. The gut microbiota regulates intestinal CD4 T cells expressing ROR gammatandcontrols metabolic disease. Cell Metab. 2015; 22: 100–112.doi:10.1016/j.cmet.2015.06.001.
59. Ivey K.L., Hodgson J.M., Kerr D.A., Lewis J.R., Thompson P.L., Prince R.L. The effects of probiotic bacteria on glycaemic control in overweight men and women: a randomised controlled trial. Eur J. Clin. Nutr.2014; 68:447–452.doi:10.1038/ejcn.2013.294.
60. Rajkumar H., Mahmood N., Kumar M., Varikuti S.R., Challa H.R., Myakala S.P. Effect of probiotic (VSL#3) and omega-3 on lipid profile, insulin sensitivity, inflammatory markers, and gut colonization in overweight adults: a randomized, controlled trial. Mediators Inflamm. 2014; 2014: 348959. doi:10.1155/2014/348959.
61. Sanchez M., Darimont C., Drapeau V., Emady-Azar S., Lepage M., Rezzonico E. et al. Effect of Lactobacillus rhamnosus CGMCC1.3724 supplementation on weight loss and maintenance in obese men and women. Br. J. Nutr. 2014; 111: 1507–1519. doi:10.1017/S0007114513003875.