mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-POS-1905mimmun-1905Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESОсобенности субпопуляционного состава регуляторных Т-лимфоцитов и микробиоты кишечника при синдроме раздраженного кишечникаProfile of subpopulation composition of regulatory T lymphocytes and intestinal microbiota in patients with irritable bowel syndromehttps://orcid.org/0000-0002-2569-6660ЕрмоленкоЕ. И.ErmolenkoE. I.

Ермоленко Елена Игоревна — докторр медицинских наук, доцент, заведующая лабораторией биомедицинской микроэкологии отдела молекулярной микробиологии ИЭМ; профессор кафедры физиологии СПбГУ.

197376, Санкт-Петербург, ул. Акад. Павлова, 12, Тел.: 8 (812) 234-68-68, Факс: 8 (812) 234-94-89

PhD, MD (Medicine), Associate Professor, Head, Laboratory of Biomedical Microecology, Department of Molecular Microbiology, IEM; Professor, Department of Physiology, St.PSU.

St. Petersburg

lermolenko1@yandex.ruhttps://orcid.org/0000-0001-7204-7850КудрявцевИ. В.KudryavtsevI. V.

Кудрявцев Игорь Владимирович — кандидат биологических наук, старший научный сотрудник отдела иммунологии ИЭМ; доцент кафедры иммунологии Первый Санкт-Петербургский ГМУ им. академика И.П. Павлова.

PhD (Biology), Senior Research Associate, Department of Immunology, IEM; Associate Professor, Department of Immunology, First St. Petersburg State I. Pavlov MU.

igorek1981@yandex.ruСоловьеваО. И.SolovyovaO. I.

Соловьева Ольга Ивановна — кандидат медицинских наук, доцент кафедры внутренних болезней, клинической фармакологии и нефрологии СЗГМУ им. И.И. Мечникова.

PhD (Medicine), Associate Professor, Department of Internal Diseases, Clinical Pharmacology and Nephrology, North-Western State I. Mechnikov MU.

o_solovjova@inbox.ruhttps://orcid.org/0000-0002-9570-4769КарасеваА. Б.KarasevaA. B.

Карасева Алена Борисовна — научный сотрудник отдела молекулярной микробиологии.

Research Associate, Department of Molecular Microbiology.

tarno@list.ruЦапиеваА. Н.TsapievaA. N.

Научный сотрудник отдела молекулярной микробиологии.

Research Associate, Department of Molecular Microbiology.

St. Petersburg

КондратенкоЮ. Д.KondratenkoYu. D.

Программист лаборатории «Центр алгоритмической биотехнологии», Институт трансляционной биомедицины СПбГУ.

Software Engineer, Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, St.PSU.

St. Petersburg, Russian Federation

КотылеваМ. П.KotylevaM. P.

Научный сотрудник отдела молекулярной микробиологии ИЭМ.

Санкт-Петербург

Research Associate, Department of Molecular Microbiology.

СеребряковаМ. К.SerebryakovaM. K.

Научный сотрудник отдела иммунологии ИЭМ.

Research Associate, Department of Immunology.

ШумихинаИ. А.ShumikhinaI. A.

Старший лаборант кафедры внутренних болезней, клинической фармакологии и нефрологии СЗГМУ им. И.И. Мечникова.

Санкт-Петербург

Senior Laboratory Assistant, Department of Internal Diseases, Clinical Pharmacology and Nephrology, N-WS I. Mechnikov MU.

СуворовА. Н.SuvorovA. N.

Докторр медицинских наук, член-корр. РАН, заведующий отделом молекулярной микробиологии ИЭМ; заведующий кафедрой фундаментальных проблем медицины и медицинской технологии СПбГУ.

Санкт-Петербург

PhD, MD (Medicine), Сorresponding Member, Russian Academy of Sciences, Head, Department of Molecular Microbiology, IEM; Head, Department of Fundamental Medicine and Medical Technologies, St.PSU.

ФГБНУ Институт экспериментальной медицины; ФГБОУВО Санкт-Петербургский государственный университетРоссияФГБНУ Институт экспериментальной медицины; ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФРоссияInstitute of Experimental Medicine; St. Petersburg State University; First St. Petersburg State I. Pavlov Medical UniversityRussian FederationФГБОУ ВО «Северо-Западный государственный медицинский университет имени И.И. Мечникова» Министерства здравоохранения РФРоссияNorth-Western State I. Mechnikov Medical UniversityRussian FederationФГБНУ Институт экспериментальной медициныРоссияInstitute of Experimental MedicineRussian FederationФГБНУ Институт экспериментальной медицинРоссияInstitute of Experimental MedicineRussian FederationФГБОУВО Санкт-Петербургский государственный университетРоссияSt. Petersburg State UniversityRussian FederationФГБНУ Институт экспериментальной медицины; ФГБОУВО Санкт-Петербургский государственный университетРоссияInstitute of Experimental Medicine; St. Petersburg State UniversityRussian Federation202014042020222335346Copyright © Ермоленко Е.И., Кудрявцев И.В., Соловьева О.И., Карасева А.Б., Цапиева А.Н., Кондратенко Ю.Д., Котылева М.П., Серебрякова М.К., Шумихина И.А., Суворов А.Н., 20202020Ермоленко Е.И., Кудрявцев И.В., Соловьева О.И., Карасева А.Б., Цапиева А.Н., Кондратенко Ю.Д., Котылева М.П., Серебрякова М.К., Шумихина И.А., Суворов А.Н.Ermolenko E.I., Kudryavtsev I.V., Solovyova O.I., Karaseva A.B., Tsapieva A.N., Kondratenko Y.D., Kotyleva M.P., Serebryakova M.K., Shumikhina I.A., Suvorov A.N.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/1905

При помощи метагеномного анализа (16 S rRNA) выявлены особенности соcтава кишечного микробиоценоза у больных синдромом раздраженного кишечника (СРК): 1) увеличение представительства Actinobacteria, в том числе Bifidobacterium spp., Firmicutes, в том числе принадлежащих к семействам Streptococcaceae (Streptococcus), Lachnosperaceae (Dorea), Veillonellaceae (Dialister), Proteobacteria (семейства Enterobacteriaceae и Desulfovibrionaceae); 2) уменьшение популяции Bacteroidetes, в том числе представителей семейств Prevotellacea (Prevotella spp.), Bacteroidaceae (Bacteroides spp.), фирмикутных бактерий, относящихся к семействам Clostridiaceae и Ruminococcaceae (Fecalibacterium spp.). Проточная цитометрия при исследовании субпопуляционного состава T регуляторных (Тreg) лимфоцитов выявила у больных СРК увеличение количества CD45R0+CD62L+ клеток центральной памяти (СМ), способных регулировать процессы созревания и дифференцировки лимфоцитов в лимфоидной ткани. Обнаружено снижение экспрессии экзонуклеаз CD39 и CD73, что может оказывать существенное влияние на их активность. Отмечено снижение эффекторных клеток памяти (ЕМ) Тreg.

Изменения в уровне экспрессии экзонуклеаз CD39 и CD73 находились в обратной корреляционной связи с содержанием протеобактерий и представительством родов Bifidobactrium и Faecalibacterium. Количественное содержание СМ Treg находилось в прямой корреляционной связи с содержанием Dorea spp.

Полученные результаты могут указывать на нарушения в процессах дифференцировки Тreg, которые тесно связаны с изменениями ключевых компонентов кишечного микробиоценоза при СРК.

The following specificcharacteristics of the composition of intestinal microbiota in patients with irritable bowel syndrome (IBS) were identified using a metagenomic analysis (16 S rRNA): 1) an increase in the representation of Actinobacteria, including Bifidobacterium spp., Firmicutes, including representatives of Streptococcaceae (Streptococcus), Lachnosperaceae (Dorea), Veillonellaceae (Dialister), Proteobacteria (Enterobacteriaceae and Desulfovibrionaceae families); 2) a decrease in the population of Bacteroidetes, including representatives of the families Prevotellacea (Prevotella spp.), Bacteroidaceae (Bacteroides spp.). Firmicutes belonging to the families Clostridiaceae and Ruminococcaceae (Fecalibacterium spp.).

Flow cytometry in the study of the subpopulation composition of T regulatory (Treg) lymphocytes in patients with IBS revealed an increase in the number of CD45R0+CD62L+ central memory cells (CM), which can regulate the processes of maturation and differentiation of lymphocytes in lymphoid tissue. A decrease in the expression of exonucleases CD39 and CD73 was detected, which can have a significant effect on their activity. A reduction in effector memory cells (EM) Treg was observed.

Changes in the expression level of exonucleases CD39 and CD73 were inversely correlated with the content of Proteobacteria and the representation of the genera Bifidobacterium spp. and Faecalibacterium spp. The content of СЫ Treg was directly correlated with the content of Dorea spp.

The results may be indicative of impairment in the processes of Treg differentiation, which are closely related to changes in key components of intestinal microbiocenosis in IBS.

кишечный микробиоценозметагеномный анализпроточная цитометрия субпопуляции Т-лимфоцитовintestinal microbiocenosismetagenomic analysisflow cytometry of a subpopulation of T lymphocytesThe work is supported by the grant of RPF 16-1510085ReferencesAkehurst R.L., Brazier J.E., Mathers N., O’Keefe C., Kaltenthaler E., Morgan A., Platts M., Walters S.J. Health-related quality of life and cost impact of irritable bowel syndrome in a UK primary care setting. Pharmacoeconomics, 2002, Vol. 20, no. 7, pp. 455-462.Akehurst R.L., Brazier J.E., Mathers N., O’Keefe C., Kaltenthaler E., Morgan A., Platts M., Walters S.J. Health-related quality of life and cost impact of irritable bowel syndrome in a UK primary care setting. Pharmacoeconomics, 2002, Vol. 20, no. 7, pp. 455-462.Averina O.V., Ermolenko E.I., Ratushniy A.Yu., Tarasova E.A., Borschev Yu.Yu., Leontieva G.F., Kramskaya T.A., Kotyleva M.P., Danilenko V.N., Suvorov A.N. Effect of probiotics on the production of cytokines in the systems in vitro. Medical Immunology (Russia), 2015, Vol. 17, no. 5, pp. 443-454. doi: 10.15789/1563-0625-2015-5-443-454.Averina O.V., Ermolenko E.I., Ratushniy A.Yu., Tarasova E.A., Borschev Yu.Yu., Leontieva G.F., Kramskaya T.A., Kotyleva M.P., Danilenko V.N., Suvorov A.N. Effect of probiotics on the production of cytokines in the systems in vitro. Medical Immunology (Russia), 2015, Vol. 17, no. 5, pp. 443-454. doi: 10.15789/1563-0625-2015-5-443-454.Belmer S.V. Immunological aspects of irritable bowel syndrome. Physician, 2016, no. 8, pp. 14-18.Belmer S.V. Immunological aspects of irritable bowel syndrome. Physician, 2016, no. 8, pp. 14-18.Chong P.P., Chin V.K., Looi C.Y., Wong W.F., Madhavan P, Yong V.C. The Microbiome and irritable bowel syndrome - a review on the pathophysiology, current research and future therapy. Front. Microbiol., 2019, Vol. 10, 1136. doi: 10.3389/fmicb.2019.01136.Chong P.P., Chin V.K., Looi C.Y., Wong W.F., Madhavan P, Yong V.C. The Microbiome and irritable bowel syndrome - a review on the pathophysiology, current research and future therapy. Front. Microbiol., 2019, Vol. 10, 1136. doi: 10.3389/fmicb.2019.01136.Drossman D.A., Hasler W.L. Rome IV - Functional GI disorders: disorders of gut-brain interaction. Gastroenterology, 2016, Vol. 150, no. 6, pp. 1257-1261.Drossman D.A., Hasler W.L. Rome IV - Functional GI disorders: disorders of gut-brain interaction. Gastroenterology, 2016, Vol. 150, no. 6, pp. 1257-1261.Eeckhaut V, Machiels K., Perrier C., Romero C., Maes S., Flahou B., Steppe M., Haesebrouck F., Sas B., Ducatelle R., Vermeire S., van Immerseel F. Butyricicoccus pullicaecorum in inflammatory bowel disease. Gut, 2013, Vol. 62, no. 12, pp. 1745-1752.Eeckhaut V, Machiels K., Perrier C., Romero C., Maes S., Flahou B., Steppe M., Haesebrouck F., Sas B., Ducatelle R., Vermeire S., van Immerseel F. Butyricicoccus pullicaecorum in inflammatory bowel disease. Gut, 2013, Vol. 62, no. 12, pp. 1745-1752.Forshammar J., Isaksson S., Strid H., Stotzer P.O., Sjbvall H., Simren M., Ohman L. A pilot study of colonic B cell pattern in irritable bowel syndrome. Scand. J. Gastroenterol., 2008, Vol. 43, no. 12, pp. 1461-1466.Forshammar J., Isaksson S., Strid H., Stotzer P.O., Sjbvall H., Simren M., Ohman L. A pilot study of colonic B cell pattern in irritable bowel syndrome. Scand. J. Gastroenterol., 2008, Vol. 43, no. 12, pp. 1461-1466.Golovkin A.S., Asadullina I.A., Kudryavtsev I.V. Purinergic regulation of basic physiological and pathological processes. Meditsinskaya immunologiya = Medical Immunology (Russia), 2018, Vol. 20, no. 4, pp. 463-476. doi: 10.15789/1563-0625-2018-4-463-476.Golovkin A.S., Asadullina I.A., Kudryavtsev I.V. Purinergic regulation of basic physiological and pathological processes. Meditsinskaya immunologiya = Medical Immunology (Russia), 2018, Vol. 20, no. 4, pp. 463-476. doi: 10.15789/1563-0625-2018-4-463-476.Gonsalkorale W.M., Perrey C., Pravica V, Whorwell P.J., Hutchinson I.V. Interleukin 10 genotypes in irritable bowel syndrome: evidence for an inflammatory component? Gut, 2003, Vol. 52, no. 1, pp. 91-93.Gonsalkorale W.M., Perrey C., Pravica V, Whorwell P.J., Hutchinson I.V. Interleukin 10 genotypes in irritable bowel syndrome: evidence for an inflammatory component? Gut, 2003, Vol. 52, no. 1, pp. 91-93.Grant C.R., Liberal R., Mieli-Vergani G., Vergani D., Longhi M.S. Regulatory T-cells in autoimmune diseases: challenges, controversies and - yet - unanswered questions. Autoimmun. Rev., 2015, Vol. 14, pp. 105-116.Grant C.R., Liberal R., Mieli-Vergani G., Vergani D., Longhi M.S. Regulatory T-cells in autoimmune diseases: challenges, controversies and - yet - unanswered questions. Autoimmun. Rev., 2015, Vol. 14, pp. 105-116.Hod K., Ringel-Kulka T., Martin C.F., Maharshak N., Ringel Y. High-sensitive C-reactive protein as a marker for inflammation in irritable bowel syndrome. J. Clin. Gastroenterol., 2016, Vol. 50, no. 3, pp. 227-232.Hod K., Ringel-Kulka T., Martin C.F., Maharshak N., Ringel Y. High-sensitive C-reactive protein as a marker for inflammation in irritable bowel syndrome. J. Clin. Gastroenterol., 2016, Vol. 50, no. 3, pp. 227-232.Holmen N., Isaksson S., Simren M., Sjbvall H., Ohman L. CD4+CD25+ regulatory T cells in irritable bowel syndrome patients. Neurogastroenterol. Motil., 2007, Vol. 19, no. 2, pp. 119-125.Holmen N., Isaksson S., Simren M., Sjbvall H., Ohman L. CD4+CD25+ regulatory T cells in irritable bowel syndrome patients. Neurogastroenterol. Motil., 2007, Vol. 19, no. 2, pp. 119-125.Ivashkin V.T., Maev I.V., Sheptulin A.A., Trukhmanov A.S., Alexeyeva O.P., Baranskaya E.K., Ivashkin K.V., Kalinin A.V., Korochanskaya N.V., Kucherya Y.A., Lapina T.L., Plotnikova E.Y., Poluektova E.A., Simanenkov V.I., Partova, A.V. Tkachev O.A., Shifrin O.S., Tarasova L.V., Khlynov I.B. Resolution of Advisory council “How to improve treatment results functional dyspepsia and irritable bowel syndrome”? Russian Journal of Gastroenterology, Hepatology, Coloproctology, 2016, no. 2, pp. 101-104.Ivashkin V.T., Maev I.V., Sheptulin A.A., Trukhmanov A.S., Alexeyeva O.P., Baranskaya E.K., Ivashkin K.V., Kalinin A.V., Korochanskaya N.V., Kucherya Y.A., Lapina T.L., Plotnikova E.Y., Poluektova E.A., Simanenkov V.I., Partova, A.V. Tkachev O.A., Shifrin O.S., Tarasova L.V., Khlynov I.B. Resolution of Advisory council “How to improve treatment results functional dyspepsia and irritable bowel syndrome”? Russian Journal of Gastroenterology, Hepatology, Coloproctology, 2016, no. 2, pp. 101-104.Kassinen A., Krogius-Kurikka L., Makivuokko H., Rinttila T., Paulin L., Corander J., Malinen E., Apajalahti J., Palva A. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology, 2007, Vol. 133, no. 1, pp. 24-33.Kassinen A., Krogius-Kurikka L., Makivuokko H., Rinttila T., Paulin L., Corander J., Malinen E., Apajalahti J., Palva A. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology, 2007, Vol. 133, no. 1, pp. 24-33.Kim H.Y., Kim T.S., Kim B.H. Degradation of organic sulfur compounds and the reduction of dibenzothiophene to biphenyl and hydrogen sulfide by Desulfovibrio desulfuricans M6. Biotechnol. Let., 1990, Vol. 12, no. 10, pp. 761-764.Kim H.Y., Kim T.S., Kim B.H. Degradation of organic sulfur compounds and the reduction of dibenzothiophene to biphenyl and hydrogen sulfide by Desulfovibrio desulfuricans M6. Biotechnol. Let., 1990, Vol. 12, no. 10, pp. 761-764.Khaydukov S.V., Baydun L.A., Zurochka A.V., Totolian Areg A. Standardized technology “Research of subpopulation composition of peripheral blood lymphocytes using pro-tread cytofluorimeters-analyzers” (Project). Medical Immunology (Russia), 2012, Vol. 14, no. 3, pp. 255-268. doi: 10.15789/1563-0625-2012-3-255-268.Khaydukov S.V., Baydun L.A., Zurochka A.V., Totolian Areg A. Standardized technology “Research of subpopulation composition of peripheral blood lymphocytes using pro-tread cytofluorimeters-analyzers” (Project). Medical Immunology (Russia), 2012, Vol. 14, no. 3, pp. 255-268. doi: 10.15789/1563-0625-2012-3-255-268.Kindt S., van Oudenhove L., Broekaert D., Kasran A., Ceuppens J.L., Bossuyt X., Fischler B., Tack J. Immune dysfunction in patients with functional gastrointestinal disorders. Neurogastroenterol. Motil., 2009, Vol. 21, no. 4, pp. 389-398.Kindt S., van Oudenhove L., Broekaert D., Kasran A., Ceuppens J.L., Bossuyt X., Fischler B., Tack J. Immune dysfunction in patients with functional gastrointestinal disorders. Neurogastroenterol. Motil., 2009, Vol. 21, no. 4, pp. 389-398.Kudryavtsev I.V., Ermolenko E.I., Solovyova O.I., Serebryakova M.K., Shumikhina I.A., Suvorov A.N. Subpopulation composition oft-lymphocytes in irritable bowel syndrome. Experimental and Clinical Gastroenterology (Russia), 2019, no. 5, pp. 22-28.Kudryavtsev I.V., Ermolenko E.I., Solovyova O.I., Serebryakova M.K., Shumikhina I.A., Suvorov A.N. Subpopulation composition oft-lymphocytes in irritable bowel syndrome. Experimental and Clinical Gastroenterology (Russia), 2019, no. 5, pp. 22-28.Lovell R.M., Ford A.C. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin. Gastroenterol. Hepatol., 2012, Vol. 10, no. 7, pp. 712-721.Lovell R.M., Ford A.C. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin. Gastroenterol. Hepatol., 2012, Vol. 10, no. 7, pp. 712-721.Lucas K. Role of the Toll like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway. Mol. Neurobiol., 2013, Vol. 48, pp. 190-204.Lucas K. Role of the Toll like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway. Mol. Neurobiol., 2013, Vol. 48, pp. 190-204.Mazmanian S.K. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature, 2008, Vol. 453, pp. 620-625.Mazmanian S.K. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature, 2008, Vol. 453, pp. 620-625.Miquel S., Martin R., Rossi O., Bermudez-Humaran L., Chatel J., Sokol H., Thomas M., Wells J., Langella P Faecalibacterium prausnitzii and human intestinal health. Curr. Opin. Microbiol., 2013, Vol. 16, no. 3, pp. 255-261.Miquel S., Martin R., Rossi O., Bermudez-Humaran L., Chatel J., Sokol H., Thomas M., Wells J., Langella P Faecalibacterium prausnitzii and human intestinal health. Curr. Opin. Microbiol., 2013, Vol. 16, no. 3, pp. 255-261.Nasser Y., Petes C., Simmers C., Basso L., Altier C., Gee K., Vanner S.J.. Activation of peripheral blood CD4+ T-cells in IBS is not associated with gastrointestinal or psychological symptoms. Sci. Rep., 2019, Vol. 9, no. 1, 3710. doi: 10.1038/s41598-019-40124-5.Nasser Y., Petes C., Simmers C., Basso L., Altier C., Gee K., Vanner S.J.. Activation of peripheral blood CD4+ T-cells in IBS is not associated with gastrointestinal or psychological symptoms. Sci. Rep., 2019, Vol. 9, no. 1, 3710. doi: 10.1038/s41598-019-40124-5.Nurkhametova D., Kudryavtsev I., Khayrutdinova O., Serebryakova M., Altunbaev R., Malm T., Giniatullin R. Purinergic profiling of regulatory T-cells in patients with episodic migraine. Front. Cell. Neurosci., 2018, Vol. 12, 326. doi: 10.3389/fncel.2018.00326.Nurkhametova D., Kudryavtsev I., Khayrutdinova O., Serebryakova M., Altunbaev R., Malm T., Giniatullin R. Purinergic profiling of regulatory T-cells in patients with episodic migraine. Front. Cell. Neurosci., 2018, Vol. 12, 326. doi: 10.3389/fncel.2018.00326.Pozuelo M., Panda S., Santiago A., Mendez S., Accarino A., Santos J., Guarner F., Azpiroz F., Manichanh C. Reduction of butyrate-and methane-producing microorganisms in patients with Irritable Bowel Syndrome. Sci. Rep., 2015, Vol. 5, 12693. doi: 10.1038/srep12693.Pozuelo M., Panda S., Santiago A., Mendez S., Accarino A., Santos J., Guarner F., Azpiroz F., Manichanh C. Reduction of butyrate-and methane-producing microorganisms in patients with Irritable Bowel Syndrome. Sci. Rep., 2015, Vol. 5, 12693. doi: 10.1038/srep12693.Rajilic-Stojanovic M., Biagi E., Heilig H.G., Kajander K., Kekkonen R.A., Tims S., de Vos W.M. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology, 2011, Vol. 141, no. 5, pp. 1792-1801.Rajilic-Stojanovic M., Biagi E., Heilig H.G., Kajander K., Kekkonen R.A., Tims S., de Vos W.M. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology, 2011, Vol. 141, no. 5, pp. 1792-1801.Rigsbee L., Agans R., Shankar V., Kenche H., Khamis H.J., Michail S., Paliy O. Quantitative profiling of gut microbiota of children with diarrhea-predominant irritable bowel syndrome. Am. J. Gastroenterol., 2012, Vol. 107, no. 11, pp. 1740-1751.Rigsbee L., Agans R., Shankar V., Kenche H., Khamis H.J., Michail S., Paliy O. Quantitative profiling of gut microbiota of children with diarrhea-predominant irritable bowel syndrome. Am. J. Gastroenterol., 2012, Vol. 107, no. 11, pp. 1740-1751.Rissiek A., Baumann I., Cuapio A., Mautner A., Kolster M., Arck P.C., Dodge-Khatami A., Mittrucker H.W., Koch-Nolte F., Haag F., Tolosa E. The expression of CD39 on regulatory T cells is genetically driven and further upregulated at sites of inflammation. J. Autoimmun., 2015, Vol. 58, pp. 12-20.Rissiek A., Baumann I., Cuapio A., Mautner A., Kolster M., Arck P.C., Dodge-Khatami A., Mittrucker H.W., Koch-Nolte F., Haag F., Tolosa E. The expression of CD39 on regulatory T cells is genetically driven and further upregulated at sites of inflammation. J. Autoimmun., 2015, Vol. 58, pp. 12-20.Rodes L., Khan A., Paul A., Coussa-Charley M., Marinescu D., Tomaro-Duchesneau C., Shao W., Kahouli I., Prakash S. Effect of probiotics Lactobacillus and Bifidobacterium on gut-derived lipopolysaccharides and inflammatory cytokines: an in vitro study using a human colonic microbiota model. J. Microbiol. Biotechnol., 2013, Vol. 23, pp. 518-526.Rodes L., Khan A., Paul A., Coussa-Charley M., Marinescu D., Tomaro-Duchesneau C., Shao W., Kahouli I., Prakash S. Effect of probiotics Lactobacillus and Bifidobacterium on gut-derived lipopolysaccharides and inflammatory cytokines: an in vitro study using a human colonic microbiota model. J. Microbiol. Biotechnol., 2013, Vol. 23, pp. 518-526.Sakaguchi S., Miyara M., Costantino C.M., Hafler D.A. FOXP3+ regulatory T cells in the human immune system. Nat. Rev. Immunol., 2010, Vol. 10, pp. 490-500.Sakaguchi S., Miyara M., Costantino C.M., Hafler D.A. FOXP3+ regulatory T cells in the human immune system. Nat. Rev. Immunol., 2010, Vol. 10, pp. 490-500.Schirmer M., Smeekens S.P., Vlamakis H., Jaeger M., Oosting M., Franzosa E.A., Ter Horst R., Jansen T., Jacobs L., Bonder M.J., Kurilshikov A., Fu J., Joosten L.A.B., Zhernakova A., Huttenhower C., Wijmenga C., Netea M.G., Xavier R.J. Linking the human gut microbiome to inflammatory cytokine production capacity. Cell, 2016, Vol. 167, no. 4, pp. 1125-1136.Schirmer M., Smeekens S.P., Vlamakis H., Jaeger M., Oosting M., Franzosa E.A., Ter Horst R., Jansen T., Jacobs L., Bonder M.J., Kurilshikov A., Fu J., Joosten L.A.B., Zhernakova A., Huttenhower C., Wijmenga C., Netea M.G., Xavier R.J. Linking the human gut microbiome to inflammatory cytokine production capacity. Cell, 2016, Vol. 167, no. 4, pp. 1125-1136.Sitkin S.I., Tkachenko E.I., Vakhitov T.Ya. Metabolic bowel dysbiosis and its biomarkers. Experimental and Clinical Gastroenterology, 2015, no. 12, pp. 6-29.Sitkin S.I., Tkachenko E.I., Vakhitov T.Ya. Metabolic bowel dysbiosis and its biomarkers. Experimental and Clinical Gastroenterology, 2015, no. 12, pp. 6-29.Smith P.M., Howitt M.R., Panikov N., Michaud M., Gallini C.A., Bohlooly-Y M., Glickman J.N., Garrett W.S. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science, 2013, Vol. 341, pp. 569-573.Smith P.M., Howitt M.R., Panikov N., Michaud M., Gallini C.A., Bohlooly-Y M., Glickman J.N., Garrett W.S. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science, 2013, Vol. 341, pp. 569-573.Solovyova O.I., Simanenkov V.I., Suvorov A.N., Ermolenko E.I., Shumihina I.A., Svirido D.A. Use of probiotics and pre-probiotics in the treatment ofirritable bowel syndrome. Experimental and Clinical Gastroenterology (Russia), 2017, no. 7, pp. 115-120.Solovyova O.I., Simanenkov V.I., Suvorov A.N., Ermolenko E.I., Shumihina I.A., Svirido D.A. Use of probiotics and pre-probiotics in the treatment ofirritable bowel syndrome. Experimental and Clinical Gastroenterology (Russia), 2017, no. 7, pp. 115-120.Suzuki D., Ueki A., Amaishi A., Ueki K. Desulfovibrio portus sp. nov., a novel sulfate-reducing bacterium in the class Deltaproteobacteria isolated from an estuarine sediment. J. Gen. Appl. Microbiol., 2009, Vol. 55, no. 2, pp. 125-133.Suzuki D., Ueki A., Amaishi A., Ueki K. Desulfovibrio portus sp. nov., a novel sulfate-reducing bacterium in the class Deltaproteobacteria isolated from an estuarine sediment. J. Gen. Appl. Microbiol., 2009, Vol. 55, no. 2, pp. 125-133.Tana C., Umesaki Y., Imaoka A., Handa T., Kanazawa M., Fukudo S. Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. Neurogastroenterol. Motil., 2010, Vol. 22, no. 5, pp. 512-519.Tana C., Umesaki Y., Imaoka A., Handa T., Kanazawa M., Fukudo S. Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. Neurogastroenterol. Motil., 2010, Vol. 22, no. 5, pp. 512-519.Tap J., Derrien M., Tbrnblom H., Brazeilles R., Cools-Portier S., Dore J., Stbrsrud S., le Neve B., Ohman L., Simren M. Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology, 2017, Vol. 152, pp. 111-123.Tap J., Derrien M., Tbrnblom H., Brazeilles R., Cools-Portier S., Dore J., Stbrsrud S., le Neve B., Ohman L., Simren M. Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology, 2017, Vol. 152, pp. 111-123.Taras D., Simmering R., Collins M.D., Lawson P.A., Blaut M. Reclassification of Eubacterium formicigenerans Holdeman and Moore 1974 as Dorea formicigenerans gen. nov., comb. nov., and description of Dorea longicatena sp. nov., isolated from human faeces. Int. J. Syst. Evol. Microbiol., 2002, Vol. 52, Pt 2, pp. 423-428.Taras D., Simmering R., Collins M.D., Lawson P.A., Blaut M. Reclassification of Eubacterium formicigenerans Holdeman and Moore 1974 as Dorea formicigenerans gen. nov., comb. nov., and description of Dorea longicatena sp. nov., isolated from human faeces. Int. J. Syst. Evol. Microbiol., 2002, Vol. 52, Pt 2, pp. 423-428.

The authors declare that there are no conflicts of interest present.