<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" 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" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">medsovet</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинский Совет</journal-title><trans-title-group xml:lang="en"><trans-title>Meditsinskiy sovet = Medical Council</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2079-701X</issn><issn pub-type="epub">2658-5790</issn><publisher><publisher-name>REMEDIUM GROUP Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.21518/2079-701X-2020-10-92-100</article-id><article-id custom-type="elpub" pub-id-type="custom">medsovet-5726</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>АЛЛЕРГОЛОГИЯ И ИММУНОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ALLERGOLOGY AND IMMUNOLOGY</subject></subj-group></article-categories><title-group><article-title>Микробиота кишечника как ключевой фактор формирования иммунитета и толерантности. Возможности пробиотиков</article-title><trans-title-group xml:lang="en"><trans-title>Intestinal microbiota as a key factor in the formation of immunity and tolerance. Probiotics capabilities</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2743-1460</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Корниенко</surname><given-names>Е. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kornienko</surname><given-names>E. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Корниенко Елена Александровна, д.м.н., профессор кафедры детских болезней имени профессора И.М. Воронцова факультета послевузовского и дополнительного профессионального образования</p><p>192100, Санкт-Петербург, ул. Литовская, д. 2</p></bio><bio xml:lang="en"><p>Elena A. Kornienko, Dr. of Sci. (Med.), Professor of the Department of Children’s Diseases named after Professor I.M. Vorontsov of the Faculty of Postgraduate and Additional Professional Education</p><p>2, Litovskaya St., St Petersburg, 194100</p></bio><email xlink:type="simple">elenkornienk@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Санкт-Петербургский государственный педиатрический медицинский университет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>St Petersburg State Pediatric University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>29</day><month>07</month><year>2020</year></pub-date><volume>0</volume><issue>10</issue><fpage>92</fpage><lpage>100</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Корниенко Е.А., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Корниенко Е.А.</copyright-holder><copyright-holder xml:lang="en">Kornienko E.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.med-sovet.pro/jour/article/view/5726">https://www.med-sovet.pro/jour/article/view/5726</self-uri><abstract><p>Введение. Микробиом кишечника является неотъемлемой частью здоровья его хозяина и выполняет несколько важнейших функций: метаболическую, координирующую, защитную, эпигенетическую, которые тесно взаимосвязаны. В условиях дисбиоза нарушение этих функций способствует формированию патологии.Иммунная система кишечника находится в постоянном взаимодействии с микробиотой. Она представлена всеми иммунными клетками: Т- и В-лимфоцитами, Т-регуляторными (Tr), дендритными клетками, макрофагами. Микропрезентация антигенов происходит через М-клетки, расположенные между эпителиоцитами. На мембране эпителия представлены Toll-подобные рецепторы, распознающие паттерны микробных клеток. Дендритные клетки осуществляют презентацию этих антигенов Т-клеткам и направляют дальнейший адаптивный иммунный ответ.Иммунная система созревает в результате заселения кишечника микробиотой, что подтверждено экспериментально на животных-гнотобионтах. В физиологических условиях она обеспечивает толерантность к собственной микробиоте посредством Tr-клеток. При дисбиозе толерогенное действие уменьшается, в результате развивается воспаление.</p><p>Состояние кишечного барьера. Кишечный барьер поддерживается микробиотой, которая стимулирует синтез муцина и клаудина. При дисбиозе усиливается проницаемость, а иммунная система подвергается атаке микробов и их метаболитов, что способствует воспалению.Дисбиоз предрасполагает к развитию воспалительных заболеваний кишечника, колоректального рака, метаболического синдрома и ожирения, пищевой аллергии. Микробиота при этих заболеваниях теряет свое разнообразие и богатство и оказывает преимущественно провоспалительное действие.</p><p>Влияние пробиотиков на иммунную систему. Пробиотики за счет адгезии в слизистый слой усиливают барьерные функции, взаимодействуют с иммунной системой, влияют на дендритные клетки, способствуя образованию Tr и препятствуя активации ядерного фактора воспаления NF-kB. Метаболиты комменсалов, в частности бутират, усиливают привлечение в толстую кишку Tr-клеток, оказывая толерогенное действие.</p><p>Показания к назначению пробиотиков. Enterococcus faecium и Bifidobacterium longum доказали действие, аналогичное нормальной кишечной микробиоте, и свою эффективность в лечении дисбиоза у детей и взрослых.</p></abstract><trans-abstract xml:lang="en"><p>Introduction. The intestinal microbiome is an integral part of the health of its owner and performs several important functions: metabolic, coordinating, protective, epigenetic, which are closely interactive. In conditions of dysbiosis, disturbances of these functions contributes to different disorders.The intestinal immune system closely interacts with the microbiota. It is represented by all cells: T- and B-lymphocytes, T-regulatory, dendritic cells, macrophages. Micropresentation of antigens occurs through M-cells located between enterocytes. Toll-like receptors that recognize bacterial patterns are presented on the epithelial membrane. Dendritic cells present these antigens to T-cells and direct a further adaptive immune response.The immune system matures as a result of colonization of the intestine with microbiota, which is confirmed experimentally in gnotobiotic animals. Under physiological conditions, the immune system provides tolerance to its own microbiota through Tr-cells. Tolerogenic effects decrease in dysbiotic conditions, as a result, inflammation develops.</p><p>The state of the intestinal barrier. The intestinal barrier is maintained by microbiota, which stimulates the synthesis of mucin and claudine. In dysbiosis, permeability increases, and the immune system is attacked by microbes and their metabolites, which contributes to inflammation.Dysbiosis predisposes to the development of inflammatory bowel diseases, colorectal cancer, metabolic syndrome and obesity, food allergies. In these diseases, the microbiota loses its diversity and richness and has a predominantly pro-inflammatory effect.</p><p>The effect of probiotics on the immune system. Probiotics, due to adhesion to the mucous layer, enhance barrier functions, interact with the immune system, affect dendritic cells, promoting the formation of Tr and inhibiting the activation of NF-kB. Commensal metabolites (butyrate) increase the involvement of Tr cells in the colon, exerting a tolerogenic effect.</p><p>Indications for the appointment of probiotics. Enterococcus faecium and Bifidobacterium longum have proven their activities similar to normal microbiota, and effectiveness in treatment of dysbiosis in children and adults.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>микробиота</kwd><kwd>иммунитет</kwd><kwd>толерантность</kwd><kwd>пробиотики</kwd><kwd>Enterococcus faecium</kwd><kwd>Bifidobacterium longum</kwd></kwd-group><kwd-group xml:lang="en"><kwd>microbiota</kwd><kwd>immunity</kwd><kwd>tolerance</kwd><kwd>probiotics</kwd><kwd>Enterococcus faecium</kwd><kwd>Bifidobacterium longum</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Статья публикуется при поддержке компании ООО «Пфайзер Инновации», что не повлияло на результаты исследования.</funding-statement><funding-statement xml:lang="en">The article is published with the support of Pfizer Innovations LLC, the support did not affect the research results.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Shi N., Li N., Duan X., Niu H. Interaction between the gut microbiome and mucosal immune system. Military Medical Research. 2017;4:59. doi: 10.1186/s40779-017-0122-9.</mixed-citation><mixed-citation xml:lang="en">Shi N., Li N., Duan X., Niu H. Interaction between the gut microbiome and mucosal immune system. Military Medical Research. 2017;4:59. doi: 10.1186/s40779-017-0122-9.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Clavel T., Lagkouvardos I., Gomes-Neto J.C., Ramer-Tait A.E. Deciphering interactions between the gut microbiota and the immune system via microbial cultivation and minimal microbiomes. Immunol. Rev. 2017;279(1):8–22. doi: 10.1111/imr.12578.</mixed-citation><mixed-citation xml:lang="en">Clavel T., Lagkouvardos I., Gomes-Neto J.C., Ramer-Tait A.E. Deciphering interactions between the gut microbiota and the immune system via microbial cultivation and minimal microbiomes. Immunol. Rev. 2017;279(1):8–22. doi: 10.1111/imr.12578.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Rios D., Wood M.B., Li J., Chassaing B., Gewirtz A.T., Williams I.R. Antigen sampling by intestinal M cells is the principal pathway initiating mucosal IgA production to commensal enteric bacteria. Mucosal Immunol. 2016;9(4):907–916. doi: 10.1038/mi.2015.121.</mixed-citation><mixed-citation xml:lang="en">Rios D., Wood M.B., Li J., Chassaing B., Gewirtz A.T., Williams I.R. Antigen sampling by intestinal M cells is the principal pathway initiating mucosal IgA production to commensal enteric bacteria. Mucosal Immunol. 2016;9(4):907–916. doi: 10.1038/mi.2015.121.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Tilg H., Moschen A.R. Food, immunity, and the microbiome. Gastroenterology. 2015;148(6):1107–1119. doi: 10.1053/j.gastro.2014.12.036.</mixed-citation><mixed-citation xml:lang="en">Tilg H., Moschen A.R. Food, immunity, and the microbiome. Gastroenterology. 2015;148(6):1107–1119. doi: 10.1053/j.gastro.2014.12.036.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Bjerke G.A., Wilson R., Storro O., Oyen T., Johnsen R., Rudi K. Mother-tochild transmission of and multiple-strain colonisation by Bacteroides fragilis in a cohort of mothers and their children. Applied and Environmental Microbiology. 2011;77(23):8318–8324. doi: 10.1128/AEM.05293-11.</mixed-citation><mixed-citation xml:lang="en">Bjerke G.A., Wilson R., Storro O., Oyen T., Johnsen R., Rudi K. Mother-tochild transmission of and multiple-strain colonisation by Bacteroides fragilis in a cohort of mothers and their children. Applied and Environmental Microbiology. 2011;77(23):8318–8324. doi: 10.1128/AEM.05293-11.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Penders J., Thijs C., Vink C., Stelma F.F., Snijders B., Kummeling I. et al. Factors Influencing the Composition of the Intestinal Microbiota in Early Infancy. Pediatrics. 2006;118(2):511–521. doi: 10.1542/peds.2005-2824.</mixed-citation><mixed-citation xml:lang="en">Penders J., Thijs C., Vink C., Stelma F.F., Snijders B., Kummeling I. et al. Factors Influencing the Composition of the Intestinal Microbiota in Early Infancy. Pediatrics. 2006;118(2):511–521. doi: 10.1542/peds.2005-2824.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Riedel C.U., Foata F., Philippe D., Adolfsson O., Eikmanns B.J., Blum S. AntiInflammatory Effects of Bifidobacteria by Inhibition of LPS-Induced NF-kappaB Activation. World Journal of Gastroenterology. 2006;12(23):3729–3735. doi: 10.3748/wjg.v12.i23.3729.</mixed-citation><mixed-citation xml:lang="en">Riedel C.U., Foata F., Philippe D., Adolfsson O., Eikmanns B.J., Blum S. AntiInflammatory Effects of Bifidobacteria by Inhibition of LPS-Induced NF-kappaB Activation. World Journal of Gastroenterology. 2006;12(23):3729–3735. doi: 10.3748/wjg.v12.i23.3729.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Round J.L., Mazmanian S.K. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci U.S.A. 2010;107(27):12204–12209. doi: 10.1073/pnas.0909122107.</mixed-citation><mixed-citation xml:lang="en">Round J.L., Mazmanian S.K. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci U.S.A. 2010;107(27):12204–12209. doi: 10.1073/pnas.0909122107.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Quévrain E., Maubert M.A., Michon C., Chain F., Marquant R., Talihades J. et al. Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn’s disease. Gut. 2016;65:415–425. doi: 10.1136/gutjnl-2014-307649.</mixed-citation><mixed-citation xml:lang="en">Quévrain E., Maubert M.A., Michon C., Chain F., Marquant R., Talihades J. et al. Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn’s disease. Gut. 2016;65:415–425. doi: 10.1136/gutjnl-2014-307649.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Vaishnava S., Behrendt C.L., Ismail A.S., Eckmann L., Hooper L.V. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbe interface. Proc Natl Acad Sci USA. 2008;105(52):20858–20863. doi: 10.1073/pnas.0808723105.</mixed-citation><mixed-citation xml:lang="en">Vaishnava S., Behrendt C.L., Ismail A.S., Eckmann L., Hooper L.V. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbe interface. Proc Natl Acad Sci USA. 2008;105(52):20858–20863. doi: 10.1073/pnas.0808723105.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Gaboriau-Routhiau V., Rakotobe S., Lécuyer E., Mulder I., Lan A., Bridonneau C. et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity. 2009;31(4):677–689. doi: 10.1016/j.immuni.2009.08.020.</mixed-citation><mixed-citation xml:lang="en">Gaboriau-Routhiau V., Rakotobe S., Lécuyer E., Mulder I., Lan A., Bridonneau C. et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity. 2009;31(4):677–689. doi: 10.1016/j.immuni.2009.08.020.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Kim Y.S., Ho S.B. Intestinal goblet cells and mucins in health and disease: Recent insights and progress. Curr Gastroenterol Rep. 2010;12(5):319–330. doi: 10.1007/s11894-010-0131-2.</mixed-citation><mixed-citation xml:lang="en">Kim Y.S., Ho S.B. Intestinal goblet cells and mucins in health and disease: Recent insights and progress. Curr Gastroenterol Rep. 2010;12(5):319–330. doi: 10.1007/s11894-010-0131-2.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Petersson J., Schreiber O., Velcich A., Roos S., Holm L., Phillipson M. et al. Importance and regulation of the colonic mucus barrier in a mouse model of colitis. Am J Physiol: Liver Physiol. 2011;300(2):327–333. doi: 10.1152/ajpgi.00422.2010.</mixed-citation><mixed-citation xml:lang="en">Petersson J., Schreiber O., Velcich A., Roos S., Holm L., Phillipson M. et al. Importance and regulation of the colonic mucus barrier in a mouse model of colitis. Am J Physiol: Liver Physiol. 2011;300(2):327–333. doi: 10.1152/ajpgi.00422.2010.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Willemsen L.E.M., Koetsier M.A., Van Deventer S.J.H., Van Tol E.A.F. Short chain fatty acids stimulate epithelial mucin 2 expression through dierential effects on prostaglandin E1 and E2 production by intestinal myofibroblasts. Gut. 2003;52(10):1442–1447. doi: 10.1136/gut.52.10.1442.</mixed-citation><mixed-citation xml:lang="en">Willemsen L.E.M., Koetsier M.A., Van Deventer S.J.H., Van Tol E.A.F. Short chain fatty acids stimulate epithelial mucin 2 expression through dierential effects on prostaglandin E1 and E2 production by intestinal myofibroblasts. Gut. 2003;52(10):1442–1447. doi: 10.1136/gut.52.10.1442.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Koren O., Goodrich J.K., Cullender T.C., Spor A., Laitinen K., Bäckhed H.K. et al. Host Remodeling of the gut microbiome and metabolic changes during pregnancy. Cell. 2012;150(3):470–480. doi: 10.1016/j.cell.2012.07.008.</mixed-citation><mixed-citation xml:lang="en">Koren O., Goodrich J.K., Cullender T.C., Spor A., Laitinen K., Bäckhed H.K. et al. Host Remodeling of the gut microbiome and metabolic changes during pregnancy. Cell. 2012;150(3):470–480. doi: 10.1016/j.cell.2012.07.008.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Kriss M., Hazleton K.Z., Nusbacher N.M., Martin C.G., Lozupone C.A. Low Diversity gut microbiota dysbiosis: Drivers, functional implications and recovery. Curr Opin Microbiol. 2018;44:34–40. doi: 10.1016/j.mib.2018.07.003.</mixed-citation><mixed-citation xml:lang="en">Kriss M., Hazleton K.Z., Nusbacher N.M., Martin C.G., Lozupone C.A. Low Diversity gut microbiota dysbiosis: Drivers, functional implications and recovery. Curr Opin Microbiol. 2018;44:34–40. doi: 10.1016/j.mib.2018.07.003.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Miyoshi J., Chang E.B. The gut microbiota and inflammatory bowel diseases. Transl Res. 2017;179:38–48. doi: 10.1016/j.trsl.2016.06.002.</mixed-citation><mixed-citation xml:lang="en">Miyoshi J., Chang E.B. The gut microbiota and inflammatory bowel diseases. Transl Res. 2017;179:38–48. doi: 10.1016/j.trsl.2016.06.002.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Kostic A.D., Xavier R.J., Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology. 2014;146(6):1489–1499. doi: 10.1053/j.gastro.2014.02.009.</mixed-citation><mixed-citation xml:lang="en">Kostic A.D., Xavier R.J., Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology. 2014;146(6):1489–1499. doi: 10.1053/j.gastro.2014.02.009.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Williams J.E., Price W.J., Shafii B., Yahvah K.M., Bode L., McGuire M.A., McGuire M.K. Relationships among Microbial Communities, Maternal Cells, Oligosaccharides, and Macronutrients in Human Milk. J Hum Lact. 2017;33(3):540–551. doi: 10.1177/0890334417709433.</mixed-citation><mixed-citation xml:lang="en">Williams J.E., Price W.J., Shafii B., Yahvah K.M., Bode L., McGuire M.A., McGuire M.K. Relationships among Microbial Communities, Maternal Cells, Oligosaccharides, and Macronutrients in Human Milk. J Hum Lact. 2017;33(3):540–551. doi: 10.1177/0890334417709433.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Ananthakrishnan A.N., Khalili H., Konijeti G.G., Higuchi L.M., de Silva P., Korzenik J.R. et al. A prospective study of long-term intake of dietary fiber and risk of Crohn’s disease and ulcerative colitis. Gastroenterology. 2013;145(5):970–977. doi: 10.1053/j.gastro.2013.07.050.</mixed-citation><mixed-citation xml:lang="en">Ananthakrishnan A.N., Khalili H., Konijeti G.G., Higuchi L.M., de Silva P., Korzenik J.R. et al. A prospective study of long-term intake of dietary fiber and risk of Crohn’s disease and ulcerative colitis. Gastroenterology. 2013;145(5):970–977. doi: 10.1053/j.gastro.2013.07.050.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Moss A., Nalankilli K. The association between diet and colorectal cancer risk: Moving beyond generalizations. Gastroenterology. 2017;152(8):18211823. doi: 10.1053/j.gastro.2017.04.025.</mixed-citation><mixed-citation xml:lang="en">Moss A., Nalankilli K. The association between diet and colorectal cancer risk: Moving beyond generalizations. Gastroenterology. 2017;152(8):18211823. doi: 10.1053/j.gastro.2017.04.025.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Gianfredi V., Salvatori T., Villarini M., Moretti M., Nucci D., Realdon S. Is dietary fibre truly protective against colon cancer? A systematic review and meta-analysis. Int J Food Sci Nutr. 2018;69(8):904–915. doi: 10.1080/09637486.2018.1446917.</mixed-citation><mixed-citation xml:lang="en">Gianfredi V., Salvatori T., Villarini M., Moretti M., Nucci D., Realdon S. Is dietary fibre truly protective against colon cancer? A systematic review and meta-analysis. Int J Food Sci Nutr. 2018;69(8):904–915. doi: 10.1080/09637486.2018.1446917.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Lazaridis N., Germanidis G. Current insights into the innate immune system dysfunction in irritable bowel syndrome. Ann Gastroenterol. 2018;31(2):171–187. doi: 10.20524/aog.2018.0229.</mixed-citation><mixed-citation xml:lang="en">Lazaridis N., Germanidis G. Current insights into the innate immune system dysfunction in irritable bowel syndrome. Ann Gastroenterol. 2018;31(2):171–187. doi: 10.20524/aog.2018.0229.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Lacy B.E., Mearin F., Chang L., Chey W.D., Lembo A.J., Simren M., Spiller R. Bowel Disorders. Gastroenterology. 2016;150(6):1393–1407. doi: 10.1053/j.gastro.2016.02.031.</mixed-citation><mixed-citation xml:lang="en">Lacy B.E., Mearin F., Chang L., Chey W.D., Lembo A.J., Simren M., Spiller R. Bowel Disorders. Gastroenterology. 2016;150(6):1393–1407. doi: 10.1053/j.gastro.2016.02.031.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">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;444:1027–1031. doi: 10.1038/nature05414.</mixed-citation><mixed-citation xml:lang="en">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;444:1027–1031. doi: 10.1038/nature05414.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Ley R.E., Turnbaugh P.J., Klein S., Gordon J.I. Microbial ecology human gut microbes associated with obesity. Nature. 2006;444:1022–1023. doi: 10.1038/4441022a.</mixed-citation><mixed-citation xml:lang="en">Ley R.E., Turnbaugh P.J., Klein S., Gordon J.I. Microbial ecology human gut microbes associated with obesity. Nature. 2006;444:1022–1023. doi: 10.1038/4441022a.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Collado M.C., Isolauri E., Laitinen K., Salminen S. Effect of mother’s weight on infant’s microbiota acquisition, composition, and activity during pregnancy: a prospective follow-up study initiated in early pregnancy. Am J Clin Nutr. 2010;92(5):1023–1030. doi: 10.3945/ajcn.2010.29877.</mixed-citation><mixed-citation xml:lang="en">Collado M.C., Isolauri E., Laitinen K., Salminen S. Effect of mother’s weight on infant’s microbiota acquisition, composition, and activity during pregnancy: a prospective follow-up study initiated in early pregnancy. Am J Clin Nutr. 2010;92(5):1023–1030. doi: 10.3945/ajcn.2010.29877.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">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(7):1761–1772. doi: 10.2337/db06-1491.</mixed-citation><mixed-citation xml:lang="en">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(7):1761–1772. doi: 10.2337/db06-1491.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Castellazzi A.M., Valsecchi C., Caimmi S., Licari A., Marseglia A., Leoni M.C. et al. Probiotics and food allergy. Ital J Pediatr. 2013;39:47. doi: 10.1186/18247288-39-47.</mixed-citation><mixed-citation xml:lang="en">Castellazzi A.M., Valsecchi C., Caimmi S., Licari A., Marseglia A., Leoni M.C. et al. Probiotics and food allergy. Ital J Pediatr. 2013;39:47. doi: 10.1186/18247288-39-47.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Bjorksten B., Naaber P., Sepp E., Mikelsaar M. The intestinal microflora in allergic Estonian and Sweden 2-year-old children. Clin Exp Allergy. 1999;29(3):342–346. doi: 10.1046/j.1365-2222.1999.00560.x.</mixed-citation><mixed-citation xml:lang="en">Bjorksten B., Naaber P., Sepp E., Mikelsaar M. The intestinal microflora in allergic Estonian and Sweden 2-year-old children. Clin Exp Allergy. 1999;29(3):342–346. doi: 10.1046/j.1365-2222.1999.00560.x.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Nylund L., Satokari R., Nikkila J., Rajilić-Stojanović M., Kalliomäki M., Isolauri E. et al. Micriarray analysis reveals marked intestinal microbiota abberancy in infants having eczema compared to healthy children in at-risk for atopic disease. BMC Microbiology. 2013;13:12–23. doi: 10.1186/1471-2180-13-12.</mixed-citation><mixed-citation xml:lang="en">Nylund L., Satokari R., Nikkila J., Rajilić-Stojanović M., Kalliomäki M., Isolauri E. et al. Micriarray analysis reveals marked intestinal microbiota abberancy in infants having eczema compared to healthy children in at-risk for atopic disease. BMC Microbiology. 2013;13:12–23. doi: 10.1186/1471-2180-13-12.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Платонова Н.Б. Аллергия к белку коровьего молока. Педиатр. 2016;7(3):153–156. doi: 10.17816/PED73153-156.</mixed-citation><mixed-citation xml:lang="en">Platonova N.B. Allergy to cow’s milk protein. Pediatr = Pediatrician. 2016;7(3):153–156. (In Russ.) doi: 10.17816/PED73153-156.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Rakoff-Naboum S., Paglimo J., Eslami-Varzanch F., Edberg S., Medzhinov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004;118(2):229–241. doi: 10.1016/j.cell.2004.07.002.</mixed-citation><mixed-citation xml:lang="en">Rakoff-Naboum S., Paglimo J., Eslami-Varzanch F., Edberg S., Medzhinov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004;118(2):229–241. doi: 10.1016/j.cell.2004.07.002.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Yan F., Polk D.B. Probiotic bacterium prevents cytokine-induced apoptosis in intestinal epithelial cells. J Biol Chem. 2002;277(52):50959–50965. doi: 10.1074/jbc.M207050200.</mixed-citation><mixed-citation xml:lang="en">Yan F., Polk D.B. Probiotic bacterium prevents cytokine-induced apoptosis in intestinal epithelial cells. J Biol Chem. 2002;277(52):50959–50965. doi: 10.1074/jbc.M207050200.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Ouwehand A., Isolauri E., Salminen S. The role of intestinal microflora for development of the immune system in early childhood. Eur J Nutr. 2002;41(1):132–137. doi: 10.1007/s00394-002-1105-4.</mixed-citation><mixed-citation xml:lang="en">Ouwehand A., Isolauri E., Salminen S. The role of intestinal microflora for development of the immune system in early childhood. Eur J Nutr. 2002;41(1):132–137. doi: 10.1007/s00394-002-1105-4.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Righy R., Kamm M.A., Knight S.C. et al. Pathogenic bacteria stimulate colonic dendritic cells to produce pro-inflammatory IL-12 while the response to probiotic bacteria is to produce anti-inflammatory IL-10. Gut. 2002;50:70.</mixed-citation><mixed-citation xml:lang="en">Righy R., Kamm M.A., Knight S.C. et al. Pathogenic bacteria stimulate colonic dendritic cells to produce pro-inflammatory IL-12 while the response to probiotic bacteria is to produce anti-inflammatory IL-10. Gut. 2002;50:70.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Smits H.H., Engering A., van der Kleij D., Wierenga E., Kooyk Y., Kapsenberg M.L. et al. Selective probiotic bacteria induce IL-10producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J Allergy Clin Immunol. 2005;115(6):12601267. doi: 10.1016/j.jaci.2005.03.036.</mixed-citation><mixed-citation xml:lang="en">Smits H.H., Engering A., van der Kleij D., Wierenga E., Kooyk Y., Kapsenberg M.L. et al. Selective probiotic bacteria induce IL-10producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J Allergy Clin Immunol. 2005;115(6):12601267. doi: 10.1016/j.jaci.2005.03.036.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Houghteling P.D., Walker W.A. Why is initial bsterial colonization of the intestine important to infants’ and children’s health? J Pediatr Gasteroenterol Nutr. 2015;60(3):294–307. doi: 10.1097/MPG.0000000000000597.</mixed-citation><mixed-citation xml:lang="en">Houghteling P.D., Walker W.A. Why is initial bsterial colonization of the intestine important to infants’ and children’s health? J Pediatr Gasteroenterol Nutr. 2015;60(3):294–307. doi: 10.1097/MPG.0000000000000597.</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Braat H., van Den B.J., van Tol E., Hommes D., Peppelenbosch M., van Deventer S. et al. Lactobacillus rhamnosus induces peripheral hyporesponsiveness in stimulated CD4+ T cells via modulation of dendritic cell function. Am J Clin Nutr. 2004;80(6):1618–1625. doi: 10.1093/ajcn/80.6.1618.</mixed-citation><mixed-citation xml:lang="en">Braat H., van Den B.J., van Tol E., Hommes D., Peppelenbosch M., van Deventer S. et al. Lactobacillus rhamnosus induces peripheral hyporesponsiveness in stimulated CD4+ T cells via modulation of dendritic cell function. Am J Clin Nutr. 2004;80(6):1618–1625. doi: 10.1093/ajcn/80.6.1618.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Dalmasso G., Cortez F., Imbert V., Lagadec Peyron J.-F., Rampal P., Czerucka D., Groux H. Saccharomyces boulardii inhibits inflammatory bowel disease by trapping T cells in mesenteric lymph nodes. Gastroenterology. 2006;131(6):1812–1825. doi: 10.1053/j.gastro.2006.10.001.</mixed-citation><mixed-citation xml:lang="en">Dalmasso G., Cortez F., Imbert V., Lagadec Peyron J.-F., Rampal P., Czerucka D., Groux H. Saccharomyces boulardii inhibits inflammatory bowel disease by trapping T cells in mesenteric lymph nodes. Gastroenterology. 2006;131(6):1812–1825. doi: 10.1053/j.gastro.2006.10.001.</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Fang H., Elina T., Heikki A., Seppo S. Modulation of humoral immune response through probiotic intake. FEMS Immunol Med Microbiol. 2000;29(1):47–52. doi: 10.1111/j.1574-695X.2000.tb01504.x.</mixed-citation><mixed-citation xml:lang="en">Fang H., Elina T., Heikki A., Seppo S. Modulation of humoral immune response through probiotic intake. FEMS Immunol Med Microbiol. 2000;29(1):47–52. doi: 10.1111/j.1574-695X.2000.tb01504.x.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Savino F., Cordisco L., Tarasco V., Palumeri E., Calabrese R., Oggero R. et al. Lactobacillus reuteri DSM 17938 in infantile colic: a randomized doubleblind, placebo controlled trial. Pediatrics. 2010;126(3):526–533. doi: 10.1542/peds.2010-0433.</mixed-citation><mixed-citation xml:lang="en">Savino F., Cordisco L., Tarasco V., Palumeri E., Calabrese R., Oggero R. et al. Lactobacillus reuteri DSM 17938 in infantile colic: a randomized doubleblind, placebo controlled trial. Pediatrics. 2010;126(3):526–533. doi: 10.1542/peds.2010-0433.</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Bernet M.F., Brassart D., Neeser J.R., Servin A.L. Adhesion of human bifidobacterial strains to cultured human intestinal epithelial cells and inhibition of enteropathogen-cell interactions. Appl Environ Microbiol. 1993;59(12):41214128. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC195875.</mixed-citation><mixed-citation xml:lang="en">Bernet M.F., Brassart D., Neeser J.R., Servin A.L. Adhesion of human bifidobacterial strains to cultured human intestinal epithelial cells and inhibition of enteropathogen-cell interactions. Appl Environ Microbiol. 1993;59(12):41214128. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC195875.</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Bednorz C., Guenther S., Oelgeschläger K., Kinnemann B., Pieper R., Hartmann S. et al. Feeding the probiotic Enterococcus faecium strain NCIMB 10415 to piglets specifically reduces the number of Escherichia coli pathotypes that adhere to the gut mucosa. Appl Environ Microbiol. 2013;79(24):7896–7904. doi: 10.1128/AEM.03138-13.</mixed-citation><mixed-citation xml:lang="en">Bednorz C., Guenther S., Oelgeschläger K., Kinnemann B., Pieper R., Hartmann S. et al. Feeding the probiotic Enterococcus faecium strain NCIMB 10415 to piglets specifically reduces the number of Escherichia coli pathotypes that adhere to the gut mucosa. Appl Environ Microbiol. 2013;79(24):7896–7904. doi: 10.1128/AEM.03138-13.</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Silva A.M., Barbosa F.H., Duarte R., Vieira L.Q., Arantes R.M.E., Nicoli J.R. Effect of Bifidobacterium longum ingestion on experimental salmonellosis in mice. J Appl Microbiol. 2004;97(1):29–37. doi: 10.1111/j.1365-2672.2004.02265.x.</mixed-citation><mixed-citation xml:lang="en">Silva A.M., Barbosa F.H., Duarte R., Vieira L.Q., Arantes R.M.E., Nicoli J.R. Effect of Bifidobacterium longum ingestion on experimental salmonellosis in mice. J Appl Microbiol. 2004;97(1):29–37. doi: 10.1111/j.1365-2672.2004.02265.x.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Miyauchi E., Ogita T., Miyamoto J., Kawamoto S., Morita H., Ohno H. et al. Bifidobacterium longum alleviates dextran sulfate sodium-induced colitis by suppressing IL-17A response: involvement of intestinal epithelial costimulatory molecules. PLoS One. 2013;8(11):79735. doi: 10.1371/journal.pone.0079735.</mixed-citation><mixed-citation xml:lang="en">Miyauchi E., Ogita T., Miyamoto J., Kawamoto S., Morita H., Ohno H. et al. Bifidobacterium longum alleviates dextran sulfate sodium-induced colitis by suppressing IL-17A response: involvement of intestinal epithelial costimulatory molecules. PLoS One. 2013;8(11):79735. doi: 10.1371/journal.pone.0079735.</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Scharek L., Guth J., Reiter K., Weyrauch K.D., Taras D., Schwerk P. et al. Influence of a probiotic Enterococcus faecium strain on development of the immune system of sows and piglets. Vet Immunol Immunopathol. 2005;105(1-2):151–161. doi: 10.1016/j.vetimm.2004.12.022.</mixed-citation><mixed-citation xml:lang="en">Scharek L., Guth J., Reiter K., Weyrauch K.D., Taras D., Schwerk P. et al. Influence of a probiotic Enterococcus faecium strain on development of the immune system of sows and piglets. Vet Immunol Immunopathol. 2005;105(1-2):151–161. doi: 10.1016/j.vetimm.2004.12.022.</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Veir J.K., Knorr R., Cavadini C., Sherrill S.J., Benyacoub J., Satyaraj E., Lappin M.R. Effect of supplementation with Enterococcus faecium (SF68) on immune functions in cats. Vet Ther. 2007;8(4):229–238. Available at: https://pubmed.ncbi.nlm.nih.gov/18183541.</mixed-citation><mixed-citation xml:lang="en">Veir J.K., Knorr R., Cavadini C., Sherrill S.J., Benyacoub J., Satyaraj E., Lappin M.R. Effect of supplementation with Enterococcus faecium (SF68) on immune functions in cats. Vet Ther. 2007;8(4):229–238. Available at: https://pubmed.ncbi.nlm.nih.gov/18183541.</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Line J.E., Svetoch E.A., Eruslanov B.V., Perelygin V.V., Mitsevich E.V., Mitsevich I.P. et al. Isolation and purification of enterocin E-760 with broad antimicrobial activity against gram-positive and gram-negative bacteria. Antimicrob Agents Chemother. 2008;52(3):1094–1100. doi: 10.1128/AAC.01569-06.</mixed-citation><mixed-citation xml:lang="en">Line J.E., Svetoch E.A., Eruslanov B.V., Perelygin V.V., Mitsevich E.V., Mitsevich I.P. et al. Isolation and purification of enterocin E-760 with broad antimicrobial activity against gram-positive and gram-negative bacteria. Antimicrob Agents Chemother. 2008;52(3):1094–1100. doi: 10.1128/AAC.01569-06.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
