Изменения кишечной микрофлоры, ассоциированные с возрастом и образом жизни

В статье представлен обзор современной литературы, обобщающий экспериментальные и клинические данные о роли микрофлоры кишечника и ее изменениях, ассоциированных с возрастом и образом жизни. В норме микрофлора кишечника выполняет ряд важных функций: участвует в энергетическом метаболизме,  обеспечивает формирование и подержание местной иммунной системы слизистых оболочек, является источником некоторых витаминов, регулирует обратное всасывание в кишечнике желчных кислот, половых гормонов, холестерина, участвует в водно-солевом обмене и т.д. Микрофлора кишечника является своеобразным индикатором состояния макроорганизма, реагируя на возрастные, физиологические, диетические, климато-географические факторы изменением качественного и количественного состава. Все эти изменения влияют на развитие хронического вялотекущего воспаления, окислительного стресса, метаболических нарушений, которые связаны с повышенным риском развития сердечно-сосудистых заболеваний и с развитием фенотипа старения в клинической практике. Очевидно, что поддержание гомеостаза и нормального обмена веществ невозможно без восстановления разнообразия нормальных ассоциаций микроорганизмов кишечника.

1. Романцова Т.И. Эпидемия ожирения: очевидные и вероятные причины //Ожирение и метаболизм. – 2011. – №. 1. – С. 5-19. [Romantsova TI. Epidemiya ozhireniya: ochevidnye i veroyatnye prichiny. Obesity and metabolism. 2011;(1):5-19] doi: 10.14341/2071-8713-5186.

2. Bienenstock J, Gibson G, Klaenhammer TR, Walker WA, Neish AS. New insights into probiotic mechanisms. Gut Microbes. 2014;4(2):94-100. doi: 10.4161/gmic.23283.

3. Blottière HM, de Vos WM, Ehrlich SD, Doré J. Human intestinal metagenomics: state of the art and future. Current Opinion in Microbiology. 2013;16(3):232-9. doi: 10.1016/j.mib.2013.06.006.

4. Lane DJ, Pace B, Olsen GJ, Stahl DA, Sogin ML, Pace NR. Rapid determination of 16S ribosomal RNA sequences for phylogenetic analyses. Proceedings of the National Academy of Sciences. 1985;82(20):6955-9. doi: 10.1073/pnas.82.20.6955.

5. Vandamme P, Pot B, Gillis M, et al. Polyphasic taxonomy, a consensus approach to bacterial systematics. Microbiol Rev. 1996; 60(2):407-38. PMID:8801440

6. Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO. Development of the Human Infant Intestinal Microbiota. PLoS Biology. 2007;5(7):e177. doi: 10.1371/journal.pbio.0050177.

7. O'Toole PW, Claesson MJ. Gut microbiota: Changes throughout the lifespan from infancy to elderly. International Dairy Journal. 2010;20(4):281-91. doi: 10.1016/j.idairyj.2009.11.010.

8. Costello EK, Lauber CL, Hamady M, et al. Bacterial community variation in human body habitats across space and time. Science. 2009. 18; 326(5960):1694-7.

9. Sekelja M, Berget I, Næs T, Rudi K. Unveiling an abundant core microbiota in the human adult colon by a phylogroup-independent searching approach. The ISME Journal. 2010;5(3):519-31. doi: 10.1038/ismej.2010.129.

10. Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature. 2012; (486):222–227. PMID:22699611

11. Corr SC, Li Y, Riedel CU, O'Toole PW, Hill C, Gahan CGM. Bacteriocin production as a mechanism for the antiinfective activity of Lactobacillus salivarius UCC118. Proceedings of the National Academy of Sciences. 2007;104(18):7617-21. doi: 10.1073/pnas.0700440104.

12. Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An Immunomodulatory Molecule of Symbiotic Bacteria Directs Maturation of the Host Immune System. Cell. 2005;122(1):107-18. doi: 10.1016/j.cell.2005.05.007.

13. Hooper LV, Midtvedt T, Gordon JI. Howhost-Microbialinteractionsshape Thenutrientenvironment of Themammalianintestine. Annual Review of Nutrition. 2002;22(1):283-307. doi: 10.1146/annurev.nutr.22.011602.092259.

14. Uribe A, Alam M, Johansson O, Midtvedt T, Theodorsson E. Microflora modulates endocrine cells in the gastrointestinal mucosa of the rat. Gastroenterology. 1994;107(5):1259-69. doi: 10.1016/0016-5085(94)90526-6.

15. Quigley E., Thompson J. The motor response to intestinal resection: motor activity in the canine small intestine following distal resection. Gastroenterology. 1993. (105):791-798. PMID:8359650

16. Rosberg-Cody E, Ross RP, Hussey S, Ryan CA, Murphy BP, Fitzgerald GF, et al. Mining the Microbiota of the Neonatal Gastrointestinal Tract for Conjugated Linoleic Acid-Producing Bifidobacteria. Applied and Environmental Microbiology. 2004;70(8):4635-41. doi: 10.1128/aem.70.8.4635-4641.2004.

17. Ridlon JM. Bile salt biotransformations by human intestinal bacteria. The Journal of Lipid Research. 2005;47(2):241-59. doi: 10.1194/jlr.R500013-JLR200.

18. Haiser HJ, Turnbaugh PJ. Developing a metagenomic view of xenobiotic metabolism. Pharmacological Research. 2013;69(1):21-31. doi: 10.1016/j.phrs.2012.07.009.

19. Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev. 2001;81(3):1031-64. PMID:11427691

20. Hill MJ. Intestinal flora and endogenous vitamin synthesis. European Journal of Cancer Prevention. 1997;6(Supplement 1):S43-S5. doi: 10.1097/00008469-199703001-00009.

21. Manco M, Putignani L, Bottazzo GF. Gut Microbiota, Lipopolysaccharides, and Innate Immunity in the Pathogenesis of Obesity and Cardiovascular Risk. Endocrine Reviews. 2010;31(6):817-44. doi: 10.1210/er.2009-0030.

22. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174-80. doi: 10.1038/nature09944.

23. Siezen RJ, Kleerebezem M. The human gut microbiome: are we our enterotypes? Microbial Biotechnology. 2011;4(5):550-3. doi: 10.1111/j.1751-7915.2011.00290.x.

24. Koren O. et al. A guide to enterotypes across the human body: meta-analysis of microbial community structures in human microbiome datasets. PLoS Comput. Biol. 2013. 9

25. Françoise Gavini CC. Differences in the Distribution of Bifidobacterial and Enterobacterial Species in Human Faecal Microflora of Three Different (Children, Adults, Elderly) Age Groups. Microbial Ecology in Health and Disease. 2001;13(1):40-5. doi: 10.1080/089106001750071690.

26. Hopkins M., Macfarlane G. Changes in predominant bacterial populations in human faeces with age and with Clostridium difficile infection. J Med Microbiol. 2002; 51(5):448–454. PMID:11990498

27. He F, Ouwehand AC, Isolauri E, Hosoda M, Benno Y, Salminen S. Differences in Composition and Mucosal Adhesion of Bifidobacteria Isolated from Healthy Adults and Healthy Seniors. Current Microbiology. 2014;43(5):351-4. doi: 10.1007/s002840010315.

28. Bartosch S, Fite A, Macfarlane GT, McMurdo MET. Characterization of Bacterial Communities in Feces from Healthy Elderly Volunteers and Hospitalized Elderly Patients by Using Real-Time PCR and Effects of Antibiotic Treatment on the Fecal Microbiota. Applied and Environmental Microbiology. 2004;70(6):3575-81. doi: 10.1128/aem.70.6.3575-3581.2004.

29. Hébuterne X. Gut changes attributed to ageing: effects on intestinal microflora. Current Opinion in Clinical Nutrition and Metabolic Care. 2003;6(1):49-54. doi: 10.1097/00075197-200301000-00008.

30. Woodmansey EJ. Intestinal bacteria and ageing. Journal of Applied Microbiology. 2007;102(5):1178-86. doi: 10.1111/j.1365-2672.2007.03400.x.

31. Midtvedt A-C, Midtvedt T. Production of Short Chain Fatty Acids by the Intestinal Microflora During the First 2 Years of Human Life. Journal of Pediatric Gastroenterology and Nutrition. 1992;15(4):395-403. doi: 10.1097/00005176-199211000-00005.

32. Laurin D, Brodeur J, Bourdages J, et al. Fibre intake in elderly individuals with poor masticatory performance. J Can Dent Assoc. 1994; 60(5):443–446, 449. PMID:8004522

33. Mariat D, Firmesse O, Levenez F, Guimarăes VD, Sokol H, Doré J, et al. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiology. 2009;9(1):123. doi: 10.1186/1471-2180-9-123.

34. Zoetendal EG, Rajilic-Stojanovic M, de Vos WM. High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota. Gut. 2008;57(11):1605-15. doi: 10.1136/gut.2007.133603.

35. Bartosch S, Fite A, Macfarlane GT, McMurdo MET. Characterization of Bacterial Communities in Feces from Healthy Elderly Volunteers and Hospitalized Elderly Patients by Using Real-Time PCR and Effects of Antibiotic Treatment on the Fecal Microbiota. Applied and Environmental Microbiology. 2004;70(6):3575-81. doi: 10.1128/aem.70.6.3575-3581.2004.

36. Filippoa С, Cavalieria D, Paolab M. et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europeand rural Africa. PNAS. 2010. 107(33).14691—14696

37. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: Human gut microbes associated with obesity. Nature. 2006;444(7122):1022-3. doi: 10.1038/4441022a.

38. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. Nature. 2008;457(7228):480-4. doi: 10.1038/nature07540.

39. Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proceedings of the National Academy of Sciences. 2005;102(31):11070-5. doi: 10.1073/pnas.0504978102.

40. Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, et al. Human gut microbiota in obesity and after gastric bypass. Proceedings of the National Academy of Sciences. 2009;106(7):2365-70. doi: 10.1073/pnas.0812600106.

41. Schwiertz A, Taras D, Schäfer K, Beijer S, Bos NA, Donus C, et al. Microbiota and SCFA in Lean and Overweight Healthy Subjects. Obesity. 2010;18(1):190-5. doi: 10.1038/oby.2009.167.

42. Jumpertz R, Le DS, Turnbaugh PJ, Trinidad C, Bogardus C, Gordon JI, et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. American Journal of Clinical Nutrition. 2011;94(1):58-65. doi: 10.3945/ajcn.110.010132.

43. Duncan SH, Lobley GE, Holtrop G, Ince J, Johnstone AM, Louis P, et al. Human colonic microbiota associated with diet, obesity and weight loss. International Journal of Obesity. 2008;32(11):1720-4. doi: 10.1038/ijo.2008.155.

44. Jeffery IB, O'Toole PW. Diet-microbiota interactions and their implications for healthy living. Nutrients. 2013. 17;5(1):234-52

45. De Filippo C, Cavalieri D, di Paola M, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl. Acad. 2010. (107):14691–14696

46. Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488(7410):178-84. doi: 10.1038/nature11319.

47. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al. Linking Long-Term Dietary Patterns with Gut Microbial Enterotypes. Science. 2011;334(6052):105-8. doi: 10.1126/science.1208344.

48. Gummesson A, Carlsson LMS, Storlien LH, Bäckhed F, Lundin P, Löfgren L, et al. Intestinal Permeability Is Associated With Visceral Adiposity in Healthy Women. Obesity. 2011;19(11):2280-2. doi: 10.1038/oby.2011.251.

49. Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500(7464):541-6. doi: 10.1038/nature12506.

50. Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500(7464):585-8. doi: 10.1038/nature12480.

51. Barger JL, Walford RL, Weindruch R. The retardation of aging by caloric restriction: its significance in the transgenic era. Experimental Gerontology. 2003;38(11-12):1343-51. doi: 10.1016/j.exger.2003.10.017.

52. Manco M. Endotoxin as a missed link among all the metabolic abnormalities in the metabolic syndrome. Atherosclerosis. 2009;206(1):36. doi: 10.1016/j.atherosclerosis.2009.03.047.

53. Ingalls RR. CD11c/CD18, a transmembrane signaling receptor for lipopolysaccharide. Journal of Experimental Medicine. 1995;181(4):1473-9. doi: 10.1084/jem.181.4.1473.

54. Geurts L, Lazarevic V, Derrien M, et al. Altered gut microbiota and endocannabinoid system tone in obese and diabetic leptinresistant mice: impact on apelin regulation in adipose tissue. Front Microbiol 2011. (2):149.

55. Успенский Ю.П. Функция микрофлоры пищеварительного тракта. Дисбиоз кишечника. / Под ред. Е.И. Ткаченко, А.Н. Суворова. - 2007. – C.19–24 [Uspenskiy YuP. Funktsiya mikroflory pishchevaritel'nogo trakta. Disbioz kishechnika. Pod red. E.I. Tkachenko, A.N. Suvorova. 2007. 19–24]

56. Serino M, Luche E, Gres S, Baylac A, Berge M, Cenac C, et al. Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota. Gut. 2011;61(4):543-53. doi: 10.1136/gutjnl-2011-301012.

57. Amar J, Serino M, Lange C, Chabo C, Iacovoni J, Mondot S, et al. Involvement of tissue bacteria in the onset of diabetes in humans: evidence for a concept. Diabetologia. 2011;54(12):3055-61. doi: 10.1007/s00125-011-2329-8.

58. Wiedermann CJ, Kiechl S, Dunzendorfer S, Schratzberger P, Egger G, Oberhollenzer F, et al. Association of endotoxemia with carotid atherosclerosis and cardiovascular disease. Journal of the American College of Cardiology. 1999;34(7):1975-81. doi: 10.1016/s0735-1097(99)00448-9.

59. Koren O, Spor A, Felin J, Fak F, Stombaugh J, Tremaroli V, et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proceedings of the National Academy of Sciences. 2010;108(Supplement_1):4592-8. doi: 10.1073/pnas.1011383107.

60. Vlachopoulos C. Acute Systemic Inflammation Increases Arterial Stiffness and Decreases Wave Reflections in Healthy Individuals. Circulation. 2005;112(14):2193-200. doi: 10.1161/circulationaha.105.535435.