<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Almanac of Clinical Medicine</journal-id><journal-title-group><journal-title xml:lang="en">Almanac of Clinical Medicine</journal-title><trans-title-group xml:lang="ru"><trans-title>Альманах клинической медицины</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2072-0505</issn><issn publication-format="electronic">2587-9294</issn><publisher><publisher-name xml:lang="en">Moscow Regional Research and Clinical Institute (MONIKI)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">91</article-id><article-id pub-id-type="doi">10.18786/2072-0505-2015-40-12-34</article-id><article-categories><subj-group subj-group-type="toc-heading"><subject>АКТУАЛЬНАЯ ПРОБЛЕМА</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">PHYLOMETABOLIC CORE OF INTESTINAL MICROBIOTA</article-title><trans-title-group xml:lang="ru"><trans-title>ФИЛОМЕТАБОЛИЧЕСКОЕ ЯДРО МИКРОБИОТЫ КИШЕЧНИКА</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Sitkin</surname><given-names>S. I.</given-names></name><name xml:lang="ru"><surname>Ситкин</surname><given-names>С. И.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Sitkin Stanislav Igorevich – PhD, Associate Professor, Leading Research Fellow, Laboratory of Microbiology</p></bio><bio xml:lang="ru"><p>Ситкин Станислав Игоревич –  кандидат медицинских наук, доцент, ведущий научный сотрудник лаборатории микробиологии</p></bio><email>sitkins@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Tkachenko</surname><given-names>E. I.</given-names></name><name xml:lang="ru"><surname>Ткаченко</surname><given-names>Е. И.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Tkachenko Evgeniy Ivanovich – MD, PhD, Professor, Head of Chair of Internal Disease Propedeutics</p></bio><bio xml:lang="ru"><p>Ткаченко Евгений Иванович –  доктор медицинских наук, профессор, зав. кафедрой пропедевтики внутренних болезней</p></bio><email>sitkins@mail.ru</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Vakhitov</surname><given-names>T. Ya.</given-names></name><name xml:lang="ru"><surname>Вахитов</surname><given-names>Т. Я.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Vakhitov Timur Yasherovich – ScD in Biology, Head of Laboratory of Microbiology</p></bio><bio xml:lang="ru"><p>Вахитов Тимур Яшэрович –  доктор биологических наук, начальник лаборатории микробиологии</p></bio><email>sitkins@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">State Research Institute of Highly Pure Biopreparations, Saint Petersburg</institution></aff><aff><institution xml:lang="ru">Государственный научно-исследовательский институт особо чистых биопрепаратов, Санкт-Петербург</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">North-Western State Medical University named after I.I. Mechnikov, Saint Petersburg</institution></aff><aff><institution xml:lang="ru">СевероЗападный государственный медицинский университет имени И.И. Мечникова Санкт-Петербург</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2015-08-15" publication-format="electronic"><day>15</day><month>08</month><year>2015</year></pub-date><issue>40</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>12</fpage><lpage>34</lpage><history><date date-type="received" iso-8601-date="2016-02-12"><day>12</day><month>02</month><year>2016</year></date><date date-type="accepted" iso-8601-date="2016-02-12"><day>12</day><month>02</month><year>2016</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2015, Sitkin S.I., Tkachenko E.I., Vakhitov T.Y.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2015, Ситкин С.И., Ткаченко Е.И., Вахитов Т.Я.</copyright-statement><copyright-year>2015</copyright-year><copyright-holder xml:lang="en">Sitkin S.I., Tkachenko E.I., Vakhitov T.Y.</copyright-holder><copyright-holder xml:lang="ru">Ситкин С.И., Ткаченко Е.И., Вахитов Т.Я.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://almclinmed.ru/jour/article/view/91">https://almclinmed.ru/jour/article/view/91</self-uri><abstract xml:lang="en"><p>The authors  discuss the  theory  of human  superorganism and its microbiota (microbiome), whose mutualistic  interactions  is realized within the  microbiota – gut – brain axis that includes endocrine, immune and neurohumoral pathways. The newest concepts  of microbiome enterotypes and core microbiota  are  presented, which are  important  for understanding of the  role of symbiotic  microorganisms  in human  vital activities, for explanation of pathophysiology of many  chronic  human  diseases  (beyond  gastrointestinal disorders), as well as for the  search of effective therapeutic targets. As highly promising are considered  the functional approaches to studies  of microbiota  that  allowed to formulate the concept  of phylometabolic (phylofunctional) core. This is a series of evolutionally stable microorganisms  responsible  for majority of the  main microbiome  functions, such as fermentation  of polysaccharides  (glycans), production of short-chain  fatty acids (butyrate, propionate, acetate), hydrogen  utilization, production of lactate, metabolism of aminoacids, bile acids, choline, production  of vitamins and  some  biologically active substances – anti-inflammatory, anti-microbial, immunostimulatory. The authors are first to describe the main functional groups  of microorganisms  of   gut microbiota phylometabolic core, providing key metabolic functions, as well as the leading characteristics of the  phylometabolic core as such. The perspectives  of modification  of composition  and functions  of phylometabolic microbiota  core are discussed based on metabiotics  as a virtually new class of therapeutic agents. A hypothesis has been proposed that  the  ratios  between main  components of the key gut microbiota may reflect fundamental  processed  related  to a mutualistic interactions between microbiota and human body, as well as they may serve as effective biological markers of dysbiotic states  determining the  development of  various  pathologic   conditions.  For  example, the  ratio between Bacteroides spp. and  butyrate producing  bacteria  that  indirectly indicates  total numbers  of microbial genes  can be used both for assessment of chronic inflammation of various localization (starting  from inflammatory  bowel disease to fat tissue inflammation related to metabolic syndrome), and for control of treatment efficacy.</p></abstract><trans-abstract xml:lang="ru"><p>Авторы обсуждают теорию сверхорганизма человека и его микробиоты (микробиома), мутуалистические взаимоотношения между которыми реализуются в пределах оси «микробиота – кишечник – мозг», включающей в себя эндокринные, иммунные  и нейрогуморальные пути. Представлены новейшие концепции энтеротипов  микробиома  и ключевой микробиоты кишечника (ядра микробиоты), важные для понимания роли симбиотических микроорганизмов в жизнедеятельности организма  человека, объяснения  патогенеза многих хронических заболеваний  человека (не только гастроэнтерологических), а также поиска эффективных терапевтических мишеней. Показана перспективность функционально-ориентированных подходов к изучению микробиоты, позволивших выдвинуть концепцию филометаболического (филофункционального)  ядра, представляющего собой набор эволюционно стабильных видов микроорганизмов, отвечающих за большинство   основных функций микробиоты, таких как ферментация   полисахаридов   (гликанов),   продукция короткоцепочечных жирных кислот (бутират, пропионат, ацетат), утилизация  водорода, продукция лактата, метаболизм аминокислот, желчных кислот, холина, продукция  витаминов и некоторых  биологически  активных соединений – противовоспалительных, антимикробных, иммуностимулирующих. Авторами впервые описаны основные функциональные группы микроорганизмов филометаболического ядра микробиоты кишечника, обеспечивающие ключевые метаболические  функции, а также ведущие характеристики самого филометаболического  ядра.  Обсуждаются перспективы коррекции  состава  и  функций филометаболического ядра микробиоты с помощью принципиально нового класса терапевтических агентов – метабиотиков. Выдвинуто предположение, что соотношения между основными компонентами  ключевой  микробиоты  кишечника   отражают фундаментальные  процессы,  связанные с взаимодействием микробиоты и организма  человека, и  могут служить эффективными биомаркерами дисбиотических состояний, определяющих  развитие  той или иной патологии. Например, соотношение  между бактероидами и бутират-продуцирующими  бактериями, косвенно указывающее на общее количество микробных генов, может быть использовано как для оценки выраженности хронического воспаления различной  локализации  (от воспалительных заболеваний кишечника до воспалительных изменений  в жировой ткани, связанных с метаболическим синдромом), так и для контроля эффективности проводимой терапии.</p></trans-abstract><kwd-group xml:lang="en"><kwd>biomarkers of gut dysbiosis</kwd><kwd>butyrate producing bacteria</kwd><kwd>core gut microbiome</kwd><kwd>metabiotics</kwd><kwd>phylometabolic core microbiota</kwd><kwd>functional groups of microorganisms</kwd><kwd>enterotypes</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>биомаркеры дисбиоза кишечника</kwd><kwd>бутират-продуцирующие бактерии</kwd><kwd>ключевая микробиота кишечника</kwd><kwd>метабиотики</kwd><kwd>филометаболическое ядро микробиоты</kwd><kwd>функциональные группы микроорганизмов</kwd><kwd>энтеротипы</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>1. Gill SR, Pop M, Deboy RT, Eckburg PB, Turnbaugh PJ, Samuel BS, Gordon JI, Relman DA, Fraser-Liggett CM, Nelson KE. Metagenomic analysis of the human distal gut microbiome. Science. 2006;312(5778):1355–9.</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>2. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Doré J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J; MetaHIT Consortium, Bork P, Ehrlich SD, Wang J. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65. doi: 10.1038/nature08821.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>3. Bäckhed F, Fraser CM, Ringel Y, Sanders ME, Sartor RB, Sherman PM, Versalovic J, Young V, Finlay BB. Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. Cell Host Microbe. 2012;12(5):611–22. doi: 10.1016/j. chom.2012.10.012.</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>4. Rajilić-Stojanović M, de Vos WM. The first 1000 cultured species of the human gastrointestinal microbiota. FEMS Microbiol Rev. 2014;38(5):996–1047. doi: 10.1111/15746976.12075.</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>5. Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90(3):859–904. doi: 10.1152/physrev.00045.2009.</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>6. Guarner F, Malagelada JR. Gut flora in health and disease. Lancet. 2003;361(9356):512–9.</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>7. Guarnier F. The enteric microbiota. In: Grang er DN, Granger J, Morgan &amp; Claypool Life Sciences, editors. Colloquium Series on Integrated Systems Physiology: From Molecule to Function to Disease. USA: Morgan &amp; Claypool Life Sciences Publishers; 2011. p. 1–77.</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>8. Prakash S, Rodes L, Coussa-Charley M, Tomaro-Duchesneau C. Gut microbiota: nextfrontier in understanding human health and development of biotherapeutics. Biologics. 2011;5:71–86. doi: 10.2147/BTT.S19099.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>9. Maukonen J. Characterization of the human predominant fecal microbiota. With special focus on the Clostridial clusters IV and XIVa [Dissertation]. Espoo: VTT Science 26; 2012. 161 p.</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>10. Bocci V. The neglected organ: bacterial flora has a crucial immunostimulatory role. Perspect Biol Med. 1992;35(2):251–60.</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>11. Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004;101(44):15718–23.</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>12. O'Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO Rep. 2006;7(7):688–93.</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>13. Cani PD, Delzenne NM. Involvement of the gut microbiota in the development of low grade inflammation associated with obesity: focus on this neglected partner. Acta Gastroenterol Belg. 2010;73(2):267–9.</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>14. Guinane CM, Cotter PD. Role of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic or- gan. Therap Adv Gastroenterol. 2013;6(4):295– 308. doi: 10.1177/1756283X13482996.</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>15. Lederberg J. Infectious history. Science. 2000;288(5464):287–93.</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>16. Nicholson JK, Holmes E, Lindon JC, Wilson ID. The challenges of modeling mammalian biocomplexity. Nat Biotechnol. 2004;22(10): 1268–74.</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>17. Goodacre R. Metabolomics of a superorganism. J Nutr. 2007;137(1 Suppl):259S–266S.</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>18. Rosenberg E, Sharon G, Zilber-Rosenberg I. The hologenome theory of evolution contains Lamarckian aspects within a Darwinian frame- work. Environ Microbiol. 2009;11(12):2959–62. doi: 10.1111/j.1462-2920.2009.01995.x.</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>19. Sleator RD. The human superorgan ism – of microbes and men. Med Hypotheses. 2010;74(2):214–5. doi: 10.1016/j. mehy.2009.08.047.</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>20. van Duynhoven J, Vaughan EE, Jacobs DM, Kemperman RA, van Velzen EJ, Gross G, Rog er LC, Possemiers S, Smilde AK, Doré J, Westerhuis JA, Van de Wiele T. Metabolic fate of polyphenols in the human superorganism. Proc Natl Acad Sci U S A. 2011;108 Suppl 1:4531–8. doi: 10.1073/pnas.1000098107.</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>21. Марков АВ. Рождение сложности. Эволюционная биология сегодня. Неожиданные открытия и новые вопросы. М.: Астрель, Corpus; 2010. 552 с.</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>22. Burcelin R, Serino M, Chabo C, Garidou L, Pomié C, Courtney M, Amar J, Bouloumié A. Metagenome and metabolism: the tissue microbiota hypothesis. Diabetes Obes Metab. 2013;15 Suppl 3:61–70. doi: 10.1111/ dom.12157.</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>23. Равин НВ, Шестаков СВ. Геном прокариот. Вавиловский журнал генетики и селекции. 2013;17(4/2):972–84.</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>24. Wang WL, Xu SY, Ren ZG, Tao L, Jiang JW, Zheng SS. Application of metagenomics in the human gut microbiome. World J Gastroenterol. 2015;21(3):803–14. doi: 10.3748/wjg.v21.i3.803.</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>25. Xiong W, Abraham PE, Li Z, Pan C, Hettich RL. Microbial metaproteomics for characterizing the range of metabolic functions and activities of human gut microbiota. Proteomics. 2015. doi: 10.1002/pmic.201400571.</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>26. Bäckhed F, Ley RE, Sonnenburg JL, Peter son DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science. 2005;307(5717): 1915–20.</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>27. Dethlefsen L, McFall-Ngai M, Relman DA. An ecological and evolutionary perspective on human-microbe mutualism and disease. Nature. 2007;449(7164):811–8.</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>28. Белобородова НВ. Интеграция метаболизма человека и его микробиома при критических состояниях. Общая реаниматология. 2012;8(4):42–54.</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>29. Bienenstock J, Collins S. 99 Dahlem conference on infection, inflammation and chronic inflammatory disorders: psycho-neuroimmunology and the intestinal microbiota: clinical observations and basic mechanisms. Clin Exp Immunol. 2010;160(1):85–91. doi: 10.1111/j.1365-2249.2010.04124.x.</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>30. Claus SP, Ellero SL, Berger B, Krause L, Bruttin A, Molina J, Paris A, Want EJ, de Waziers I, Cloarec O, Richards SE, Wang Y, Dumas ME, Ross A, Rezzi S, Kochhar S, Van Bladeren P, Lindon JC, Holmes E, Nicholson JK. Colonization-induced host-gut microbial metabolic interaction. MBio. 2011;2(2):e00271–10. doi: 10.1128/mBio.00271-10.</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>31. Bienenstock J. Commensal communication to the brain: pathways and behavioral consequences. Microb Ecol Health Dis. 2012;23. doi: 10.3402/mehd.v23i0.19007.</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>32. Larsson E, Tremaroli V, Lee YS, Koren O, Nookaew I, Fricker A, Nielsen J, Ley RE, Bäckhed F. Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88. Gut. 2012;61(8):1124–31. doi:</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>10.1136/gutjnl-2011-301104.</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>33. Thomas LV, Ockhuizen T. New insights into the impact of the intestinal microbiota on health and disease: a symposium report. Br J Nutr. 2012;107 Suppl 1:S1–13. doi: 10.1017/ S0007114511006970.</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>34. Clarke G, Grenham S, Scully P, Fitzgerald P, Moloney RD, Shanahan F, Dinan TG, Cryan JF. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry. 2013;18(6):666–73. doi: 10.1038/ mp.2012.77.</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>35. Forsythe P, Kunze WA. Voices from within: gut microbes and the CNS. Cell Mol Life Sci. 2013;70(1):55–69. doi: 10.1007/s00018-012- 1028-z.</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>36. Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol. 2013;6(1):39–51. doi: 10.1177/1756283X12459294.</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>37. Philpott H, Gibson P, Thien F. Irritable bowel syndrome – an inflammatory disease involving mast cells. Asia Pac Allergy. 2011;1(1):36–42. doi: 10.5415/apallergy.2011.1.1.36.</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>38. Kennedy PJ, Cryan JF, Dinan TG, Clarke G. Irritable bowel syndrome: a microbiome-gut-brain axis	disorder? World J Gastroenterol. 2014;20(39):14105–25. doi: 10.3748/wjg.v20. i39.14105.</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>39. Segata N, Haake SK, Mannon P, Lemon KP, Waldron L, Gevers D, Huttenhower C, Izard J. Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biol. 2012;13(6):R42. doi: 10.1186/gb-2012-13-6-r42.</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>40. Wilson M. Bacteriology of humans: an ecological perspective. Wiley-Blackwell; 2008. 360 p.</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>41. Dicksved J, Lindberg M, Rosenquist M, Enroth H, Jansson JK, Engstrand L. Molecular characterization of the stomach microbiota in patients with gastric cancer and in controls. J Med Microbiol. 2009;58(Pt 4):509–16. doi: 10.1099/jmm.0.007302-0.</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>42. Жебрун АБ. Инфекция Helicobacter pylori. СПб.: Феникс; 2006. 380 с.</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>43. van den Bogert B, Meijerink M, Zoetendal EG, Wells JM, Kleerebezem M. Immunomodulatory properties of Streptococcus and Veillonella isolates from the human small intestine microbiota. PLoS One. 2014;9(12):e114277. doi: 10.1371/journal.pone.0114277.</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>44. Rajilić-Stojanović M, Smidt H, de Vos WM. Diversity of the human gastrointestinal tract microbiota revisited. Environ Microbiol. 2007;9(9):2125–36.</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>45. 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.</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>46. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM, Bertalan M, Borruel N, Casellas F, Fernandez L, Gautier L, Hansen T, Hattori M, Hayashi T, Kleerebezem M, Kurokawa K, Leclerc M, Levenez F, Manichanh C, Nielsen HB, Nielsen T, Pons N, Poulain J, Qin J, Sicheritz-Ponten T, Tims S, Torrents D, Ugarte E, Zoetendal EG, Wang J, Guarner F, Pedersen O, de Vos WM, Brunak S, Doré J; MetaHIT Consortium, Antolín M, Artiguenave F, Blottiere HM, Almeida M, Brechot C, Cara C, Chervaux C, Cultrone A, Delorme C, Denariaz G, Dervyn R, Foerstner KU, Friss C, van de Guchte M, Guedon E, Haimet F, Huber W, van Hylckama-Vlieg J, Jamet A, Juste C, Kaci G, Knol J, Lakhdari O, Layec S, Le Roux K, Maguin E, Mérieux A, Melo Minardi R, M'rini C, Muller J, Oozeer R, Parkhill J, Renault P, Rescigno M, Sanchez N, Sunagawa S, Torrejon A, Turner K, Vandemeulebrouck G, Varela E, Winogradsky Y, Zeller G, Weissenbach J, Ehrlich SD, Bork P. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174– 80. doi: 10.1038/nature09944.</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>47. Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO. Development of the human infant intestinal microbiota. PLoS Biol. 2007;5(7):e177.</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>48. Mariat D, Firmesse O, Levenez F, Guimarăes V, Sokol H, Doré J, Corthier G, Furet JP. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol. 2009;9:123. doi: 10.1186/1471-2180-9-123.</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>49. Biagi E, 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(5):e10667. doi: 10.1371/journal. pone.0010667.</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>50. Biagi E, Candela M, Fairweather-Tait S, Franceschi C, Brigidi P. Aging of the human metaorganism: the microbial counterpart. Age (Dordr). 2012;34(1):247–67. doi: 10.1007/s11357-011- 9217-5.</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>51. Sokol H, Seksik P, Furet JP, Firmesse O, Nion-Larmurier I, Beaugerie L, Cosnes J, Corthier G, Marteau P, Doré J. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis. 2009;15(8):1183–9. doi: 10.1002/ ibd.20903.</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>52. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444(7122):1022–3.</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>53. Harmsen HJ, Raangs GC, He T, Degener JE, Welling GW. Extensive set of 16S rRNA-based probes for detection of bacteria in human feces. Appl Environ Microbiol. 2002;68(6): 2982–90.</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>54. Swidsinski A, Loening-Baucke V, Kirsch S, Doerffel Y. Functional biostructure of colonic microbiota (central fermenting area, germinal stock area and separating mucus layer) in healthy subjects and patients with diarrhea treated with Saccharomyces boulardii. Gastroenterol Clin Biol. 2010;34 Suppl 1:S79–92. doi: 10.1016/S0399-8320(10)70025-7.</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>55. Zitomersky NL, Coyne MJ, Comstock LE. Longitudinal analysis of the prevalence, maintenance, and IgA response to species of the order Bacteroidales in the human gut. Infect Immun. 2011;79(5):2012–20. doi: 10.1128/ IAI.01348-10.</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>56. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kuczynski J, Caporaso JG, Lozupone CA, Lauber C, Clemente JC, Knights D, Knight R, Gordon JI. Human gut microbiome viewed across age and geography. Nature. 2012;486(7402):222–7. doi: 10.1038/nature11053.</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>57. Liu J, Wang H, Yang H, Zhang Y, Wang J, Zhao F, Qi J. Composition-based classification of short metagenomic sequences elucidates the landscapes of taxonomic and functional enrichment of microorganisms. Nucleic Acids Res. 2013;41(1):e3. doi: 10.1093/nar/gks828.</mixed-citation></ref><ref id="B59"><label>59.</label><mixed-citation>58. Dridi B, Henry M, El Khéchine A, Raoult D, Drancourt M. High prevalence of Methanobrevibacter smithii and Methanosphaera stadtmanae detected in the human gut using an improved DNA detection protocol. PLoS One. 2009;4(9):e7063. doi: 10.1371/journal. pone.0007063.</mixed-citation></ref><ref id="B60"><label>60.</label><mixed-citation>59. Sahakian AB, Jee SR, Pimentel M. Methane and the gastrointestinal tract. Dig Dis Sci. 2010;55(8):2135–43. doi: 10.1007/s10620-009- 1012-0.</mixed-citation></ref><ref id="B61"><label>61.</label><mixed-citation>60. Dridi B, Henry M, Richet H, Raoult D, Drancourt M. Age-related prevalence of Methanomassiliicoccus luminyensis in the human gut microbiome. APMIS. 2012;120(10):773–7. doi: 10.1111/j.1600-0463.2012.02899.x.</mixed-citation></ref><ref id="B62"><label>62.</label><mixed-citation>61. Schulze J, Sonnenborn U. Yeasts in the gut: from commensals to infectious agents. Dtsch Arztebl Int. 2009;106(51–52):837–42. doi: 10.3238/arztebl.2009.0837.</mixed-citation></ref><ref id="B63"><label>63.</label><mixed-citation>62. Авалуева ЕБ, Шевяков МА, Успенский ЮП, Нилова ЛЮ, Жигалова ТН, Суворова МА, Матвеева НВ. Кандидозный дисбиоз у пациентов с воспалительными заболевани ями кишечника и адгезивные свойства Candida spp. Проблемы медицинской микологии. 2010;12(1):10–4.</mixed-citation></ref><ref id="B64"><label>64.</label><mixed-citation>63. Reyes A, Haynes M, Hanson N, Angly FE, Heath AC, Rohwer F, Gordon JI. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature. 2010;466(7304):334–8. doi: 10.1038/nature09199.</mixed-citation></ref><ref id="B65"><label>65.</label><mixed-citation>64. Waller AS, Yamada T, Kristensen DM, Kultima JR, Sunagawa S, Koonin EV, Bork P. Classification and quantification of bacteriophage taxa in human gut metagenomes. ISME J. 2014;8(7):1391–402. doi: 10.1038/ismej.2014.30.</mixed-citation></ref><ref id="B66"><label>66.</label><mixed-citation>65. Dethlefsen L, Huse S, Sogin ML, Relman DA. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 2008;6(11):e280. doi: 10.1371/journal.pbio.0060280.</mixed-citation></ref><ref id="B67"><label>67.</label><mixed-citation>66. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal microbial flora. Science. 2005;308(5728):1635–8.</mixed-citation></ref><ref id="B68"><label>68.</label><mixed-citation>67. Flint HJ, Duncan SH, Scott KP, Louis P. Interactions and competition within the microbial community of the human colon: links between diet and health. Environ Microbiol. 2007;9(5):1101–11.</mixed-citation></ref><ref id="B69"><label>69.</label><mixed-citation>68. Xu J, Mahowald MA, Ley RE, Lozupone CA, Hamady M, Martens EC, Henrissat B, Coutinho PM, Minx P, Latreille P, Cordum H, Van Brunt A, Kim K, Fulton RS, Fulton LA, Clifton SW, Wilson RK, Knight RD, Gordon JI. Evolution of symbiotic bacteria in the distal human intestine. PLoS Biol. 2007;5(7):e156.</mixed-citation></ref><ref id="B70"><label>70.</label><mixed-citation>69. Rajilić-Stojanović M, Heilig HG, Molenaar D, Kajander K, Surakka A, Smidt H, de Vos WM. Development and application of the human intestinal tract chip, a phylogenetic microarray: analysis of universally conserved phylotypes in the abundant microbiota of young and elderly adults. Environ Microbiol. 2009;11(7):1736–51. doi: 10.1111/j.1462-2920.2009.01900.x.</mixed-citation></ref><ref id="B71"><label>71.</label><mixed-citation>70. Flint HJ, Scott KP, Louis P, Duncan SH. The role of the gut microbiota in nutrition and health. Nat Rev Gastroenterol Hepatol. 2012;9(10):577–89. doi: 10.1038/nrgastro.2012.156.</mixed-citation></ref><ref id="B72"><label>72.</label><mixed-citation>71. Martens EC, Lowe EC, Chiang H, Pudlo NA, Wu M, McNulty NP, Abbott DW, Henrissat B, Gilbert HJ, Bolam DN, Gordon JI. Recognition and degradation of plant cell wall polysaccharides by two human gut symbionts. PLoS Biol. 2011;9(12):e1001221. doi: 10.1371/journal. pbio.1001221.</mixed-citation></ref><ref id="B73"><label>73.</label><mixed-citation>72. Wright DP, Rosendale DI, Robertson AM. Prevotella enzymes involved in mucin oligosaccharide degradation and evidence for a small operon of genes expressed during growth on mucin. FEMS Microbiol Lett. 2000;190(1):73–9.</mixed-citation></ref><ref id="B74"><label>74.</label><mixed-citation>73. Greenhill AR, Tsuji H, Ogata K, Natsuhara K, Morita A, Soli K, Larkins JA, Tadokoro K, Odani S, Baba J, Naito Y, Tomitsuka E, Nomoto K, Siba PM, Horwood PF, Umezaki M. Characterization of the gut microbiota of Papua New Guineans using reverse transcription quantitative PCR. PLoS One. 2015;10(2):e0117427. doi: 10.1371/journal.pone.0117427.</mixed-citation></ref><ref id="B75"><label>75.</label><mixed-citation>74. Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol. 2004;54(Pt 5):1469–76.</mixed-citation></ref><ref id="B76"><label>76.</label><mixed-citation>75. van Passel MW, Kant R, Zoetendal EG, Plugge CM, Derrien M, Malfatti SA, Chain PS, Woyke T, Palva A, de Vos WM, Smidt H. The genome of Akkermansia muciniphila, a dedicated intestinal mucin degrader, and its use in exploring intestinal metagenomes. PLoS One. 2011;6(3):e16876. doi: 10.1371/journal. pone.0016876.</mixed-citation></ref><ref id="B77"><label>77.</label><mixed-citation>76. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, Bewtra M, Knights D, Walters WA, Knight R, Sinha R, Gilroy E, Gupta K, Baldassano R, Nessel L, Li H, Bushman FD, Lewis JD. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334(6052):105–8. doi: 10.1126/science.1208344.</mixed-citation></ref><ref id="B78"><label>78.</label><mixed-citation>77. Bushman FD, Lewis JD, Wu GD. Diet, gut enterotypes and health: is there a link? Nestle Nutr Inst Workshop Ser. 2013;77:65–73. doi: 10.1159/000351385.</mixed-citation></ref><ref id="B79"><label>79.</label><mixed-citation>78. De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, Collini S, Pieraccini G, Lionetti P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. 2010;107(33):14691–6. doi: 10.1073/pnas.1005963107.</mixed-citation></ref><ref id="B80"><label>80.</label><mixed-citation>79. Ou J, Carbonero F, Zoetendal EG, DeLany JP, Wang M, Newton K, Gaskins HR, O'Keefe SJ. Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. Am J Clin Nutr. 2013;98(1):111–20. doi: 10.3945/ajcn.112.056689.</mixed-citation></ref><ref id="B81"><label>81.</label><mixed-citation>80. Carbonero F, Zoetendal EG, Ou J, O'Keefe SJ, Gaskins HR. Mo1611 Traditional African and western diets select distinct phylogenetic and functional colonic microbiota among different populations. Gastroenterology. 2012;142(5) Suppl 1:S-641.</mixed-citation></ref><ref id="B82"><label>82.</label><mixed-citation>81. Lim MY, Rho M, Song YM, Lee K, Sung J, Ko G. Stability of gut enterotypes in Korean monozygotic twins and their association with biomarkers and diet. Sci Rep. 2014;4:7348. doi: 10.1038/srep07348.</mixed-citation></ref><ref id="B83"><label>83.</label><mixed-citation>82. Попенко АС. Биоинформационное исследование таксономического состава микробиоты кишечника человека. Автореф. дис. … канд. биол. наук. М.; 2014. 22 с.</mixed-citation></ref><ref id="B84"><label>84.</label><mixed-citation>83. Zhang J, Guo Z, Xue Z, Sun Z, Zhang M, Wang L, Wang G, Wang F, Xu J, Cao H, Xu H, Lv Q, Zhong Z, Chen Y, Qimuge S, Menghe B, Zheng Y, Zhao L, Chen W, Zhang H. A phylo-functional core of gut microbiota in healthy young Chinese cohorts across lifestyles, geography and ethnicities. ISME J. 2015;9(9):1979–90. doi: 10.1038/ismej.2015.11.</mixed-citation></ref><ref id="B85"><label>85.</label><mixed-citation>84. Holmes I, Harris K, Quince C. Dirichlet multinomial mixtures: generative models for microbial metagenomics. PLoS One. 2012;7(2):e30126. doi: 10.1371/journal.pone.0030126.</mixed-citation></ref><ref id="B86"><label>86.</label><mixed-citation>85. Claesson MJ, Jeffery IB, Conde S, Power SE, O'Connor EM, Cusack S, Harris HM, Coakley M, Lakshminarayanan B, O'Sullivan O, Fitzgerald GF, Deane J, O'Connor M, Harnedy N, O'Connor K, O'Mahony D, van Sinderen D, Wallace M, Brennan L, Stanton C, Marchesi JR, Fitzgerald AP, Shanahan F, Hill C, Ross RP, O'Toole PW. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488(7410):178–84. doi: 10.1038/ nature11319.</mixed-citation></ref><ref id="B87"><label>87.</label><mixed-citation>86. Roager HM, Licht TR, Poulsen SK, Larsen TM, Bahl MI. Microbial enterotypes, inferred by the prevotella-to-bacteroides ratio, remained stable during a 6-month randomized controlled diet intervention with the new nordic diet. Appl Environ Microbiol. 2014;80(3):1142–9. doi: 10.1128/AEM.03549-13.</mixed-citation></ref><ref id="B88"><label>88.</label><mixed-citation>87. Jacobsen UP, Nielsen HB, Hildebrand F, Raes J, Sicheritz-Ponten T, Kouskoumvekaki I, Panagiotou G. The chemical interactome space between the human host and the genetically defined gut metabotypes. ISME J. 2013;7(4):730–42. doi: 10.1038/ismej.2012.141.</mixed-citation></ref><ref id="B89"><label>89.</label><mixed-citation>88. Huse SM, Ye Y, Zhou Y, Fodor AA. A core human microbiome as viewed through 16S rRNA sequence clusters. PLoS One. 2012;7(6):e34242. doi: 10.1371/journal.pone.0034242.</mixed-citation></ref><ref id="B90"><label>90.</label><mixed-citation>89. Koren O, Knights D, Gonzalez A, Waldron L, Segata N, Knight R, Huttenhower C, Ley RE. A guide to enterotypes across the human body: meta-analysis of microbial community structures in human microbiome datasets. PLoS Comput Biol. 2013;9(1):e1002863. doi: 10.1371/journal.pcbi.1002863.</mixed-citation></ref><ref id="B91"><label>91.</label><mixed-citation>90. Jeffery IB, Claesson MJ, O'Toole PW, Shanahan F. Categorization of the gut microbiota: enterotypes or gradients? Nat Rev Microbiol. 2012;10(9):591–2.</mixed-citation></ref><ref id="B92"><label>92.</label><mixed-citation>91. Knights D, Ward TL, McKinlay CE, Miller H, Gonzalez A, McDonald D, Knight R. Rethinking “enterotypes”. Cell Host Microbe. 2014;16(4):433– 7. doi: 10.1016/j.chom.2014.09.013.</mixed-citation></ref><ref id="B93"><label>93.</label><mixed-citation>92. Суворов АН. Мир микробов и человек. Природа. 2015;(5):11–9.</mixed-citation></ref><ref id="B94"><label>94.</label><mixed-citation>93. Sanli K, Karlsson FH, Nookaew I, Nielsen J. FANTOM: Functional and taxonomic analysis of metagenomes. BMC Bioinformatics. 2013;14:38. doi: 10.1186/1471-2105-14-38.</mixed-citation></ref><ref id="B95"><label>95.</label><mixed-citation>94. Kim Y, Koh I, Rho M. Deciphering the human microbiome using next-generation sequencing data and bioinformatics approaches. Methods. 2015;79–80:52–9. doi: 10.1016/j. ymeth.2014.10.022.</mixed-citation></ref><ref id="B96"><label>96.</label><mixed-citation>95. Verberkmoes NC, Russell AL, Shah M, Godzik A, Rosenquist M, Halfvarson J, Lefsrud MG, Apajalahti J, Tysk C, Hettich RL, Jansson JK. Shotgun metaproteomics of the human distal gut microbiota. ISME J. 2009;3(2):179–89. doi: 10.1038/ismej.2008.108.</mixed-citation></ref><ref id="B97"><label>97.</label><mixed-citation>96. Rehman A, Lepage P, Nolte A, Hellmig S, Schreiber S, Ott SJ. Transcriptional activity of the dominant gut mucosal microbiota in chronic inflammatory bowel disease patients. J Med Microbiol. 2010;59(Pt 9):1114–22. doi: 10.1099/ jmm.0.021170-0.</mixed-citation></ref><ref id="B98"><label>98.</label><mixed-citation>97. Kolmeder CA, de Been M, Nikkilä J, Ritamo I, Mättö J, Valmu L, Salojärvi J, Palva A, Salonen A, de Vos WM. Comparative metaproteomics and diversity analysis of human intestinal microbiota testifies for its temporal stability and expression of core functions. PLoS One. 2012;7(1):e29913. doi: 10.1371/journal. pone.0029913.</mixed-citation></ref><ref id="B99"><label>99.</label><mixed-citation>98. Franzosa EA, Morgan XC, Segata N, Waldron L, Reyes J, Earl AM, Giannoukos G, Boylan MR, Ciulla D, Gevers D, Izard J, Garrett WS, Chan AT, Huttenhower C. Relating the metatranscriptome and metagenome of the human gut. Proc Natl Acad Sci U S A. 2014;111(22):E2329– 38. doi: 10.1073/pnas.1319284111.</mixed-citation></ref><ref id="B100"><label>100.</label><mixed-citation>99. Tap J, Mondot S, Levenez F, Pelletier E, Caron C, Furet JP, Ugarte E, Muñoz-Tamayo R, Paslier DL, Nalin R, Dore J, Leclerc M. Towards the human intestinal microbiota phylogenetic core. Environ Microbiol. 2009;11(10):2574–84. doi: 10.1111/j.1462-2920.2009.01982.x.</mixed-citation></ref><ref id="B101"><label>101.</label><mixed-citation>100. Sobhani I, Tap J, Roudot-Thoraval F, Roperch JP, Letulle S, Langella P, Corthier G, Tran Van Nhieu J, Furet JP. Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One. 2011;6(1):e16393. doi: 10.1371/journal.pone.0016393.</mixed-citation></ref><ref id="B102"><label>102.</label><mixed-citation>101. Jalanka-Tuovinen J, Salonen A, Nikkilä J, Immonen O, Kekkonen R, Lahti L, Palva A, de Vos WM. Intestinal microbiota in healthy adults: temporal analysis reveals individual and common core and relation to intestinal symptoms. PLoS One. 2011;6(7):e23035. doi: 10.1371/journal. pone.0023035.</mixed-citation></ref><ref id="B103"><label>103.</label><mixed-citation>102. Tyakht AV, Kostryukova ES, Popenko AS, Belenikin MS, Pavlenko AV, Larin AK, Karpova IY, Selezneva OV, Semashko TA, Ospanova EA, Babenko VV, Maev IV, Cheremushkin SV, Kucheryavyy YA, Shcherbakov PL, Grinevich VB, Efimov OI, Sas EI, Abdulkhakov RA, Abdulkhakov SR, Lyalyukova EA, Livzan MA, Vlassov VV, Sagdeev RZ, Tsukanov VV, Osipenko MF, Kozlova IV, Tkachev AV, Sergienko VI, Alexeev DG, Govorun VM. Human gut microbiota community structures in urban and rural populations in Russia. Nat Commun. 2013;4:2469. doi: 10.1038/ncomms3469. 103. Тяхт АВ. Функциональный анализ метагенома кишечника человека. Автореферат дис. … канд. биол. наук. М.; 2014. 22 с.</mixed-citation></ref><ref id="B104"><label>104.</label><mixed-citation>104. Thorasin T, Hoyles L, McCartney AL. Dynamics and diversity of the ‘Atopobium cluster' in the human faecal microbiota, and phenotypic characterization of ‘Atopobium cluster' isolates. Microbiology. 2015;161(Pt 3):565–79. doi: 10.1099/mic.0.000016.</mixed-citation></ref><ref id="B105"><label>105.</label><mixed-citation>105. Lukovac S, Belzer C, Pellis L, Keijser BJ, de Vos WM, Montijn RC, Roeselers G. Differential modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids. MBio. 2014;5(4). pii: e01438–14. doi: 10.1128/mBio.01438-14.</mixed-citation></ref><ref id="B106"><label>106.</label><mixed-citation>106. Bang C, Weidenbach K, Gutsmann T, Heine H, Schmitz RA. The intestinal archaea Methanosphaera stadtmanae and Methanobrevibacter smithii activate human dendritic cells. PLoS One. 2014;9(6):e99411. doi: 10.1371/journal. pone.0099411.</mixed-citation></ref><ref id="B107"><label>107.</label><mixed-citation>107. Sekelja M, Berget I, Næs T, Rudi K. Unveiling an abundant core microbiota in the human adult colon by a phylogroup-independent searching approach. ISME J. 2011;5(3):519–31. doi: 10.1038/ismej.2010.129.</mixed-citation></ref><ref id="B108"><label>108.</label><mixed-citation>108. Li K, Bihan M, Methé BA. Analyses of the stability and core taxonomic memberships of the human microbiome. PLoS One. 2013;8(5):e63139. doi: 10.1371/journal.pone.0063139.</mixed-citation></ref><ref id="B109"><label>109.</label><mixed-citation>109. Meehan CJ, Beiko RG. A phylogenomic view of ecological specialization in the Lachnospiraceae, a family of digestive tract-associated bacteria. Genome Biol Evol. 2014;6(3):703–13. doi: 10.1093/gbe/evu050.</mixed-citation></ref><ref id="B110"><label>110.</label><mixed-citation>110. Turnbaugh PJ, Quince C, Faith JJ, McHardy AC, Yatsunenko T, Niazi F, Affourtit J, Egholm M, Henrissat B, Knight R, Gordon JI. Organismal, genetic, and transcriptional variation in the deeply sequenced gut microbiomes of identical twins. Proc Natl Acad Sci U S A. 2010;107(16):7503–8. doi: 10.1073/ pnas.1002355107.</mixed-citation></ref><ref id="B111"><label>111.</label><mixed-citation>111. 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. doi: 10.1111/j.1574-6968.2009.01514.x.</mixed-citation></ref><ref id="B112"><label>112.</label><mixed-citation>112. Vital M, Howe AC, Tiedje JM. Revealing the bacterial butyrate synthesis pathways by analyzing (meta)genomic data. MBio. 2014;5(2):e00889. doi: 10.1128/mBio.00889-14.</mixed-citation></ref><ref id="B113"><label>113.</label><mixed-citation>113. Johnson JL, Moore WEC, Moore LVH. Bacteroides caccae sp. nov., Bacteroides merdae sp. nov., and Bacteroides stercoris sp. nov. Isolated from Human Feces. Int J Syst Evol Microbiol. 1986;36(4):499–501. doi: 10.1099/0020771336-4-499.</mixed-citation></ref><ref id="B114"><label>114.</label><mixed-citation>114. Chassard C, Delmas E, Lawson PA, Bernalier-Donadille A. Bacteroides xylanisolvens sp. nov., a xylan-degrading bacterium isolated from human faeces. Int J Syst Evol Microbiol. 2008;58(Pt 4):1008–13. doi: 10.1099/ ijs.0.65504-0.</mixed-citation></ref><ref id="B115"><label>115.</label><mixed-citation>115. Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: roles of resistantstarch and nonstarch polysaccharides. Physiol Rev. 2001;81(3):1031–64.</mixed-citation></ref><ref id="B116"><label>116.</label><mixed-citation>116. Rey FE, Faith JJ, Bain J, Muehlbauer MJ, Stevens RD, Newgard CB, Gordon JI. Dissecting the in vivo metabolic potential of two human gut acetogens. J Biol Chem. 2010;285(29):22082– 90. doi: 10.1074/jbc.M110.117713.</mixed-citation></ref><ref id="B117"><label>117.</label><mixed-citation>117. Reichardt N, Duncan SH, Young P, Belenguer A, McWilliam Leitch C, Scott KP, Flint HJ, Louis P. Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. ISME J. 2014;8(6):1323–35. doi: 10.1038/ismej.2014.14.</mixed-citation></ref><ref id="B118"><label>118.</label><mixed-citation>118. Salonen A, Salojärvi J, Lahti L, de Vos WM. The adult intestinal core microbiota is determined by analysis depth and health status. Clin Microbiol Infect. 2012;18 Suppl 4:16–20. doi: 10.1111/j.1469-0691.2012.03855.x.</mixed-citation></ref><ref id="B119"><label>119.</label><mixed-citation>119. Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A. 2007;104(34):13780–5.</mixed-citation></ref><ref id="B120"><label>120.</label><mixed-citation>120. Frank DN, Robertson CE, Hamm CM, Kpadeh Z, Zhang T, Chen H, Zhu W, Sartor RB, Boedeker EC, Harpaz N, Pace NR, Li E. Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. Inflamm Bowel Dis. 2011;17(1):179–84. doi: 10.1002/ibd.21339.</mixed-citation></ref><ref id="B121"><label>121.</label><mixed-citation>121. Kabeerdoss J, Sankaran V, Pugazhendhi S, Ramakrishna BS. Clostridium leptum group bacteria abundance and diversity in the fecal microbiota of patients with inflammatory bowel disease: a case-control study in India. BMC Gastroenterol. 2013;13:20. doi: 10.1186/1471-230X-13-20.</mixed-citation></ref><ref id="B122"><label>122.</label><mixed-citation>122. Naseribafrouei A, Hestad K, Avershina E, Sekelja M, Linløkken A, Wilson R, Rudi K. Correlation between the human fecal microbiota and depression. Neurogastroenterol Motil. 2014;26(8):1155–62. doi: 10.1111/nmo.12378.</mixed-citation></ref><ref id="B123"><label>123.</label><mixed-citation>123. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI. A core gut microbiome in obese and lean twins. Nature. 2009;457(7228):480–4. doi: 10.1038/nature07540.</mixed-citation></ref><ref id="B124"><label>124.</label><mixed-citation>124. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489(7415):220–30. doi: 10.1038/nature11550.</mixed-citation></ref><ref id="B125"><label>125.</label><mixed-citation>125. Doré J, Corthier G. The human intestinal microbiota. Gastroenterol Clin Biol. 2010;34 Suppl 1:S7–15. doi: 10.1016/S0399-8320(10)70015-4.</mixed-citation></ref><ref id="B126"><label>126.</label><mixed-citation>126. Lepage P, Leclerc MC, Joossens M, Mondot S, Blottière HM, Raes J, Ehrlich D, Doré J. A metagenomic insight into our gut's microbiome. Gut. 2013;62(1):146–58. doi: 10.1136/gutjnl-2011-301805.</mixed-citation></ref><ref id="B127"><label>127.</label><mixed-citation>127. Smith EA, Macfarlane GT. Formation of Phenolic and Indolic Compounds by AnaerobicBacteria in the Human Large Intestine. Microb Ecol. 1997;33(3):180–8.</mixed-citation></ref><ref id="B128"><label>128.</label><mixed-citation>128. Metges CC. Contribution of microbial amino acids to amino acid homeostasis of the host. J Nutr. 2000;130(7):1857S–64S.</mixed-citation></ref><ref id="B129"><label>129.</label><mixed-citation>129. 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.</mixed-citation></ref><ref id="B130"><label>130.</label><mixed-citation>130. Flint HJ, Scott KP, Duncan SH, Louis P, Forano E. Microbial degradation of complex carbohydrates in the gut. Gut Microbes. 2012;3(4):289–306.</mixed-citation></ref><ref id="B131"><label>131.</label><mixed-citation>131. 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. doi: 10.4291/wjgp.v3.i1.27.</mixed-citation></ref><ref id="B132"><label>132.</label><mixed-citation>132. Carmody RN, Turnbaugh PJ. Host-microbial interactions in the metabolism of therapeu tic and diet-derived xenobiotics. J Clin Invest. 2014;124(10):4173–81. doi: 10.1172/JCI72335.</mixed-citation></ref><ref id="B133"><label>133.</label><mixed-citation>133. Joice R, Yasuda K, Shafquat A, Morgan XC, Huttenhower C. Determining microbial products and identifying molecular targets in the human microbiome. Cell Metab. 2014;20(5):731– 41. doi: 10.1016/j.cmet.2014.10.003.</mixed-citation></ref><ref id="B134"><label>134.</label><mixed-citation>134. Shafquat A, Joice R, Simmons SL, Huttenhower C. Functional and phylogenetic assembly of microbial communities in the human microbiome. Trends Microbiol. 2014;22(5):261–6. doi: 10.1016/j.tim.2014.01.011.</mixed-citation></ref><ref id="B135"><label>135.</label><mixed-citation>135. Cullen TW, Schofield WB, Barry NA, Putnam EE, Rundell EA, Trent MS, Degnan PH, Booth CJ, Yu H, Goodman AL. Gut microbiota. Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation. Science. 2015;347(6218):170–5. doi: 10.1126/science.1260580.</mixed-citation></ref><ref id="B136"><label>136.</label><mixed-citation>136. Magnúsdóttir S, Ravcheev D, de Crécy-Lagard V, Thiele I. Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes. Front Genet. 2015;6:148. doi: 10.3389/fgene.2015.00148.</mixed-citation></ref><ref id="B137"><label>137.</label><mixed-citation>137. Neis EP, Dejong CH, Rensen SS. The role of microbial amino acid metabolism in host me tabolism. Nutrients. 2015;7(4):2930–46. doi: 10.3390/nu7042930.</mixed-citation></ref><ref id="B138"><label>138.</label><mixed-citation>138. Sagar NM, Cree IA, Covington JA, Arasaradnam RP. The interplay of the gut microbiome, bile acids, and volatile organic compounds. Gastroenterol Res Pract. 2015;2015:398585. doi: 10.1155/2015/398585. 146.</mixed-citation></ref><ref id="B139"><label>139.</label><mixed-citation>139. Quévrain E, Maubert MA, Michon C, Chain F, Marquant R, Tailhades J, Miquel S, Carlier L, Bermúdez-Humarán LG, Pigneur B, Lequin O, Kharrat P, Thomas G, Rainteau D, Aubry C, Breyner N, Afonso C, Lavielle S, Grill JP, Chassaing G, Chatel JM, Trugnan G, Xavier R, Langella P, Sokol H, Seksik P. Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease. Gut. 2015. pii: gutjnl-2014-307649. doi: 10.1136/gutjnl-2014-307649.</mixed-citation></ref><ref id="B140"><label>140.</label><mixed-citation>140. Cardona F, Andrés-Lacueva C, Tulipani S, Tinahones FJ, Queipo-Ortuño MI. Benefits of polyphenols on gut microbiota and implications in human health. J Nutr Biochem. 2013;24(8):1415–22. doi: 10.1016/j.jnutbio.2013.05.001.</mixed-citation></ref><ref id="B141"><label>141.</label><mixed-citation>141. Marín L, Miguélez EM, Villar CJ, Lombó F. Bioavailability of dietary polyphenols and gut microbiota metabolism: antimicrobial properties. Biomed Res Int. 2015;2015:905215. doi: 10.1155/2015/905215.</mixed-citation></ref><ref id="B142"><label>142.</label><mixed-citation>142. Rafii F. The role of colonic bacteria in the metabolism of the natural isoflavone daidzin to equol. Metabolites. 2015;5(1):56–73. doi: 10.3390/metabo5010056.</mixed-citation></ref><ref id="B143"><label>143.</label><mixed-citation>143. Kitahara M, Sakamoto M, Ike M, Sakata S, Benno Y. Bacteroides plebeius sp. nov. and Bacteroides coprocola sp. nov., isolated from human faeces. Int J Syst Evol Microbiol. 2005;55(Pt 5):2143–7.</mixed-citation></ref><ref id="B144"><label>144.</label><mixed-citation>144. Hehemann JH, Correc G, Barbeyron T, Helbert W, Czjzek M, Michel G. Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature. 2010;464(7290):908–12. doi: 10.1038/nature08937. ture08937.</mixed-citation></ref><ref id="B145"><label>145.</label><mixed-citation>145. Sánchez E, De Palma G, Capilla A, Nova E, Pozo T, Castillejo G, Varea V, Marcos A, Garrote JA, Polanco I, López A, Ribes-Koninckx C, García-Novo MD, Calvo C, Ortigosa L, Palau F, Sanz Y. Influence of environmental and genetic factors linked to celiac disease risk on infant gut colonization by Bacteroides species. Appl Environ Microbiol. 2011;77(15):5316–23. doi: 10.1128/AEM.00365-11.</mixed-citation></ref><ref id="B146"><label>146.</label><mixed-citation>146. Sitkin S, Tkachenko E, Vakhitov T, Oreshko L, Zhigalova T. Oral butyrate plus inulin improve serum metabolomic profile and gut microbiota composition in ulcerative colitis and celiac disease. J Crohns Colitis. 2014;8 Suppl 1:S232. doi: 10.1016/S1873-9946(14)60519-5.</mixed-citation></ref><ref id="B147"><label>147.</label><mixed-citation>147. Shenderov BA. Metabiotics: novel idea or natural development of probiotic conception. Microb Ecol Health Dis. 2013;24. doi: 10.3402/ mehd.v24i0.20399.</mixed-citation></ref><ref id="B148"><label>148.</label><mixed-citation>148. Pozuelo M, Panda S, Santiago A, Mendez S, Accarino A, Santos J, Guarner F, Azpiroz F, Manichanh C. Reduction of butyrateand methane-producing microorganisms in patients with Irritable Bowel Syndrome. Sci Rep. 2015;5:12693. doi: 10.1038/srep12693.</mixed-citation></ref><ref id="B149"><label>149.</label><mixed-citation>149. Nylund L, Nermes M, Isolauri E, Salminen S, de Vos WM, Satokari R. Severity of atopic disease inversely correlates with intestinal microbiota diversity and butyrate-producing bacteria. Allergy. 2015;70(2):241–4. doi: 10.1111/all.12549.</mixed-citation></ref><ref id="B150"><label>150.</label><mixed-citation>150. Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, Almeida M, Quinquis B, Levenez F, Galleron N, Gougis S, Rizkalla S, Batto JM, Renault P; ANR MicroObes consor- tium, Doré J, Zucker JD, Clément K, Ehrlich SD. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500(7464):585–8. doi: 10.1038/nature12480.</mixed-citation></ref><ref id="B151"><label>151.</label><mixed-citation>151. Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, Almeida M, Arumugam M, Batto JM, Kennedy S, Leonard P, Li J, Burgdorf K, Grarup N, Jørgensen T, Brandslund I, Nielsen HB, Juncker AS, Bertalan M, Levenez F, Pons N, Rasmussen S, Sunagawa S, Tap J, Tims S, Zoetendal EG, Brunak S, Clément K, Doré J, Kleerebezem M, Kristiansen K, Renault P, Sicheritz-Ponten T, de Vos WM, Zucker JD, Raes J, Hansen T; MetaHIT consortium, Bork P, Wang J, Ehrlich SD, Pedersen O. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500(7464):541–6. doi: 10.1038/nature12506.</mixed-citation></ref><ref id="B152"><label>152.</label><mixed-citation>152. Lepage P, Leclerc MC, Joossens M, Mondot S, Blottière HM, Raes J, Ehrlich D, Doré J. A metagenomic insight into our gut's microbiome. Gut. 2013;62(1):146–58. doi: 10.1136/gutjnl-2011-301805.</mixed-citation></ref><ref id="B153"><label>153.</label><mixed-citation>153. Sitkin S, Vakhitov T, Tkachenko E, Oreshko L, Zhigalova T. Metabolic dysbiosis concept and its biomarkers in ulcerative colitis and celiac disease. J Crohns Colitis. 2015;9 Suppl 1:S437. doi: 10.1093/ecco-jcc/jju027.829.</mixed-citation></ref><ref id="B154"><label>154.</label><mixed-citation>154. Shenderov BA, Midtvedt T. Epigenomic programing: a future way to health? Microb Ecol Health Dis. 2014;25. doi: 10.3402/mehd. v25.24145.</mixed-citation></ref></ref-list></back></article>
