medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2022-16-12-152-159medsovet-6992Research ArticleШКОЛА ПЕДИАТРАPEDIATRICIAN SCHOOLКлинические эффекты влияния пробиотиков на функционирование «оси кишечник - головной мозг» у детейClinical effects of probiotics on the functioning of the gut-brain axis in childrenhttps://orcid.org/0000-0003-4200-4598ЗахароваИ. Н.ZakharovaI. N.

Захарова Ирина Николаевна – доктор медицинских наук, профессор, заведующая кафедрой педиатрии имени академика Г.Н. Сперанского.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1.

Irina N. Zakharova - Dr. Sci. (Med.), Professor, Head of the Department of Pediatrics named after Academician G.N. Speransky, Russian Medical Academy of Continuous Professional Education.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993.

zakharova-rmapo@yandex.ruДмитриеваД. К.DmitrievaD. K.

Дмитриева Диана Кирилловна - аспирант кафедры педиатрии имени академика Г.Н. Сперанского.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1.

Diana K. Dmitrieva - Postgraduate Student of the Department of Pediatrics named after Academician G.N. Speransky, Russian Medical Academy of Continuous Professional Education.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993.

dmitrievadi@maill.ruhttps://orcid.org/0000-0002-2847-6268БережнаяИ. В.BerezhnayaI. V.

Бережная Ирина Владимировна – кандидат медицинских наук, доцент кафедры педиатрии имени академика Г.Н. Сперанского.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1.

Irina V. Berezhnaya - Cand. Sci. (Med.), Associate Professor of the Department of Pediatrics named after Academician G.N. Speransky, Russian Medical Academy of Continuous Professional Education.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993.

berezhnaya-irina26@yandex.ruСериковаЛ. С.SerikovaL. S.

Серикова Людмила Сергеевна - заведующая отделением педиатрии.

143420, Московская обл., Красногорск, п. Новый, д. 1.

Lyudmila S. Serikova - Head of Pediatrician Department, National Medical Research Center of High Medical Technologies - Central Military Clinical Hospital named after A.A. Vishnevsky.

1, Novy, Krasnogorsk, Moscow Region, 143420.

malusya4@mail.ruСугянН. Г.SugianN. G.

Сугян Нарине Григорьевна - кандидат медицинских наук, доцент кафедры педиатрии имени академика Г.Н. Сперанского.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1.

Narine G. Sugian - Cand. Sci. (Med.), Associate Professor of the Department of Pediatrics named after Academician G.N. Speransky, Russian Medical Academy of Continuous Professional Education.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993.

narine6969@mail.ruГостюхинаА. Д.GostyukhinaA. D.

Гостюхина Анастасия Дмитриева - ординатор кафедры педиатрии имени академика Г.Н. Сперанского.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1.

Anastasiya D. Gostyukhina - Resident of the Department of Pediatrics named after Academician G.N. Speransky, Russian Medical Academy of Continuous Professional Education.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993.

gostuhinaa@gmail.comРоссийская медицинская академия непрерывного профессионального образованияРоссияRussian Medical Academy of Continuous Professional EducationRussian FederationНациональный медицинский исследовательский центр высоких медицинских технологий - центральный военный клинический госпиталь имени А.А. ВишневскогоРоссияNational Medical Research Center of High Medical Technologies - Central Military Clinical Hospital named after A.A. VishnevskyRussian Federation202213072022012152159Copyright © Захарова И.Н., Дмитриева Д.К., Бережная И.В., Серикова Л.С., Сугян Н.Г., Гостюхина А.Д., 20222022Захарова И.Н., Дмитриева Д.К., Бережная И.В., Серикова Л.С., Сугян Н.Г., Гостюхина А.Д.Zakharova I.N., Dmitrieva D.K., Berezhnaya I.V., Serikova L.S., Sugian N.G., Gostyukhina A.D.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/6992

Микробиота кишечника представляет собой сложную совокупность бактерий, вирусов, простейших, архей и грибов, населяющих желудочно-кишечный тракт (ЖКТ) человека. Микробиота играет фундаментальную роль в сохранении здоровья человека и в развитии различных заболеваний, в т. ч. психических. Клинические исследования доказали существование двунаправленной связи между кишечником, микробиотой и мозгом в рамках «оси мозг - кишечник - микробиом». Предполагается, что кишечные микробы играют роль во многих психических расстройствах и могут быть потенциальной терапевтической мишенью. Нервная система и ЖКТ сообщаются через двунаправленную сеть сигнальных путей, которая состоит из множества соединений, включая блуждающий нерв, иммунную систему, гипоталамо-гипофизарно-надпочечниковую ось, некоторые трансмиттеры и бактериальные метаболиты. Имеющиеся данные свидетельствуют о взаимном влиянии микробиоты и активации воспалительных процессов в головном мозге. В случае повреждения этой связи для коррекции микробиоты в последнее время все чаще используют психобиотики. Впервые использованный в 2013 г. термин определял психобиотики как пробиотики, которые при приеме внутрь в адекватных количествах оказывают положительное влияние на психическое здоровье. В дальнейшем, учитывая продемонстрированную пользу пребиотиков, они были включены в определение. Таким образом, психобиотики - полезные бактерии (пробиотики) или вспомогательные вещества для таких бактерий (пребиотики), которые влияют на взаимоотношения между бактериями и мозгом. Пробиотические бактерии после приема внутрь концентрируются в основном в эпителии кишечника, обеспечивая хозяина питательными веществами и оказывая влияние на иммунную систему, а также производя нейроактивные вещества, которые действуют на «ось мозг - кишечник». Данный обзор посвящен новой интересной области, которая связывает микробиоту кишечника с заболеваниями нервной системы и ее возможным лечением с помощью психобиотиков.

The gut microbiota is a complex collection of bacteria, viruses, protozoa, archaea, and fungi colonising the human gastrointestinal (GI) tract. The microbiota plays a fundamental role in keeping the body healthy and the development of various diseases, including mental ones. Clinical studies have showed that there exists a bidirectional communication between the gut, microbiota and brain within the brain-gut-microbiome axis. It is understood that gut microbes play a role in many mental disorders and may be a potential therapeutic target. The nervous system and GI tract communicate through a bidirectional signalling network that includes multiple pathways, among which are the vagus nerve, the immune system, the hypothalamic-pituitary-adrenal axis, some transmitters, and bacterial metabolites. The available data indicate the mutual influence of the microbiota and the activation of inflammatory processes in the brain. Psychobiotics have been increasingly used for the management of the microbiota in case of injury of this pathway. The term that was used for the first time in 2013 defined psychobiotics as probiotics, which have a positive effect on mental health provided that they are taken orally at adequate doses.

Afterwards they were included in the definition, given the proven benefit of prebiotics. Thus, psychobiotics are beneficial bacteria (probiotics) or auxiliary substances for such bacteria (prebiotics) that affect the communication and interactions between bacteria and the brain. Following ingestion, probiotic bacteria concentrate mainly in the intestinal epithelium, providing the host with nutrients and influencing the immune system, as well as producing neuroactive substances that act on the brain-gut axis. This review is devoted to the new interesting area that correlates the gut microbiota with nervous system diseases and its possible treatment with psychobiotics.

детицентральная нервная системаголовной мозгкороткоцепочечные жирные кислотыпробиотикиchildrencentral nervous systembrainshort-chain fatty acidsprobioticsReferencesAhlawat S., Asha, Sharma K.K. Gutorgan axis: a microbial outreach and networking. Lett App Microbiol. 2020;72(6):636-668. https://doi.org/10.1111/lam.13333Ahlawat S., Asha, Sharma K.K. Gutorgan axis: a microbial outreach and networking. Lett App Microbiol. 2020;72(6):636-668. https://doi.org/10.1111/lam.13333Roger AJ., Munoz-Gomez S.A., Kamikawa R. The origin and diversification of mitochondria. Curr Biol. 2017;27(21):R1177-R1R92. https://doi.org/10.1016/j.cub.2017.09.015.Roger AJ., Munoz-Gomez S.A., Kamikawa R. The origin and diversification of mitochondria. Curr Biol. 2017;27(21):R1177-R1R92. https://doi.org/10.1016/j.cub.2017.09.015.Moloney R.D., Desbonnet L., Clarke G., Dinan T.G., Cryan J.F. The microbiome: stress, health and disease. Mamm Genome. 2014;25(1-2):49-74. https://doi.org/10.1007/s00335-013-9488-5.Moloney R.D., Desbonnet L., Clarke G., Dinan T.G., Cryan J.F. The microbiome: stress, health and disease. Mamm Genome. 2014;25(1-2):49-74. https://doi.org/10.1007/s00335-013-9488-5.Dinan T.G., Stanton C., Cryan J.F. Psychobiotics: A novel class of psychotropic. Biol Psychiatry. 2013;74(10):720-726. https://doi.org/10.1016/j.bio-psych.2013.05.001.Dinan T.G., Stanton C., Cryan J.F. Psychobiotics: A novel class of psychotropic. Biol Psychiatry. 2013;74(10):720-726. https://doi.org/10.1016/j.bio-psych.2013.05.001.Sampson T.R., Debelius J.W., Thron T., Janssen S., Shastri G.G., Ilhan Z.E. et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell. 2016;167(6):1469-1480.e12. https://doi.org/10.1016/j.cell.2016.11.018.Sampson T.R., Debelius J.W., Thron T., Janssen S., Shastri G.G., Ilhan Z.E. et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell. 2016;167(6):1469-1480.e12. https://doi.org/10.1016/j.cell.2016.11.018.Leung K., Thuret S. Gut microbiota: a modulator of brain plasticity and cognitive function in ageing. Healthcare (Basel). 2015;3(4):898-916. https://doi.org/10.3390/healthcare3040898.Leung K., Thuret S. Gut microbiota: a modulator of brain plasticity and cognitive function in ageing. Healthcare (Basel). 2015;3(4):898-916. https://doi.org/10.3390/healthcare3040898.Qin J., Li R., Raes J., Arumugam M., Burgdorf K.S., Manichanh C. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59-65. https://doi.org/10.1038/nature08821.Qin J., Li R., Raes J., Arumugam M., Burgdorf K.S., Manichanh C. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59-65. https://doi.org/10.1038/nature08821.Drossman D.A. Functional gastrointestinal disorders: history, pathophysiology, clinical features and rome IV. Gastroenterology. 2016;150(6):1262-1279.E2. https://doi.org/10.1053/j.gastro.2016.02.032.Drossman D.A. Functional gastrointestinal disorders: history, pathophysiology, clinical features and rome IV. Gastroenterology. 2016;150(6):1262-1279.E2. https://doi.org/10.1053/j.gastro.2016.02.032.Margolis K.G., Cryan J.F., Mayer E.A. The Microbiota-gut-brain axis: from motility to mood. Gastroenterology. 2021;160(5):1486-1501. https://doi.org/10.1053/j.gastro.2020.10.066.Margolis K.G., Cryan J.F., Mayer E.A. The Microbiota-gut-brain axis: from motility to mood. Gastroenterology. 2021;160(5):1486-1501. https://doi.org/10.1053/j.gastro.2020.10.066.Mayer E.A. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci. 2011;12(8):453-466. https://doi.org/10.1038/nrn3071.Mayer E.A. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci. 2011;12(8):453-466. https://doi.org/10.1038/nrn3071.Pearse A.G. The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J Histochem Cytochem. 1969;17(5):303-313. https://doi.org/10.1177/17.5.303.Pearse A.G. The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J Histochem Cytochem. 1969;17(5):303-313. https://doi.org/10.1177/17.5.303.Furness J.B., Callaghan B.P., Rivera L.R., Cho H.-J. The enteric nervous system and gastrointestinal innervation: integrated local and central control. Adv Exp Med Biol. 2014;817:39-71. https://doi.org/10.1007/978-1-4939-0897-4_3.Furness J.B., Callaghan B.P., Rivera L.R., Cho H.-J. The enteric nervous system and gastrointestinal innervation: integrated local and central control. Adv Exp Med Biol. 2014;817:39-71. https://doi.org/10.1007/978-1-4939-0897-4_3.Sundman E., Olofsson P.S. Neural control of the immune system. Adv Physiol Educ. 2014;38(2):135-139. https://doi.org/10.1152/advan.00094.2013.Sundman E., Olofsson P.S. Neural control of the immune system. Adv Physiol Educ. 2014;38(2):135-139. https://doi.org/10.1152/advan.00094.2013.Dinan T.G., Cryan J.F. Regulation of the stress response by the gut microbiota: Implications for psychoneuroendocrinology. Psychoneuroendocrinology. 2012;37(9):1369-1378. https://doi.org/10.1016/j.psyneuen.2012.03.007.Dinan T.G., Cryan J.F. Regulation of the stress response by the gut microbiota: Implications for psychoneuroendocrinology. Psychoneuroendocrinology. 2012;37(9):1369-1378. https://doi.org/10.1016/j.psyneuen.2012.03.007.Carabotti M., Scirocco A., Maselli M.A., Severi C. The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015;28(2):203-209. Available at: https://pubmed.ncbi.nlm.nih.gov/25830558/.Carabotti M., Scirocco A., Maselli M.A., Severi C. The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015;28(2):203-209. Available at: https://pubmed.ncbi.nlm.nih.gov/25830558/.Bermudez-Humaran L.G., Salinas E., Ortiz G.G., Ramirez-Jirano LJ., Morales J.A., Bitzer-Quintero O.K. From probiotics to psychobiotics: live beneficial bacteria which act on the brain-gut axis. Nutrients. 2019;11(4):890. https://doi.org/10.3390/nu11040890.Bermudez-Humaran L.G., Salinas E., Ortiz G.G., Ramirez-Jirano LJ., Morales J.A., Bitzer-Quintero O.K. From probiotics to psychobiotics: live beneficial bacteria which act on the brain-gut axis. Nutrients. 2019;11(4):890. https://doi.org/10.3390/nu11040890.Cryan J.F., O'Riordan K.J., Cowan C.S.M., Sandhu K.V., Bastiaanssen T.F.S., Boehme M. et al. The Microbiota-Gut-Brain Axis. Physiol Rev. 2019;99(4):1877-2013. https://doi.org/10.1152/physrev.00018.2018.Cryan J.F., O'Riordan K.J., Cowan C.S.M., Sandhu K.V., Bastiaanssen T.F.S., Boehme M. et al. The Microbiota-Gut-Brain Axis. Physiol Rev. 2019;99(4):1877-2013. https://doi.org/10.1152/physrev.00018.2018.Borre Y.E., O'Keeffe G.W., Clarke G., Stanton C., Dinan T.G., Cryan J.F. Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med. 2014;20(9):509-518. https://doi.org/10.1016/j.molmed.2014.05.002.Borre Y.E., O'Keeffe G.W., Clarke G., Stanton C., Dinan T.G., Cryan J.F. Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med. 2014;20(9):509-518. https://doi.org/10.1016/j.molmed.2014.05.002.Yano J.M., Yu K., Donaldson G.P., Shastri G.G., Ann P., Ma L. et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161(2):264-276. https://doi.org/10.1016/j.cell.2015.02.047.Yano J.M., Yu K., Donaldson G.P., Shastri G.G., Ann P., Ma L. et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161(2):264-276. https://doi.org/10.1016/j.cell.2015.02.047.Gershon M.D. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes. 2013;20(1):14-21. https://doi.org/10.1097/MED.0b013e32835bc703.Gershon M.D. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes. 2013;20(1):14-21. https://doi.org/10.1097/MED.0b013e32835bc703.Dissanayake D., Hall H., Berg-Brown N., Elford A.R., Hamilton S.R., Murakami K. et al. Nuclear factor-kB1 controls the functional maturation of dendritic cells and prevents the activation of autoreactive T cells. Nat Med. 2011;17(12):1663-1667. https://doi.org/10.1038/nm.2556.Dissanayake D., Hall H., Berg-Brown N., Elford A.R., Hamilton S.R., Murakami K. et al. Nuclear factor-kB1 controls the functional maturation of dendritic cells and prevents the activation of autoreactive T cells. Nat Med. 2011;17(12):1663-1667. https://doi.org/10.1038/nm.2556.Wishart D.S., Feunang Y.D., Marcu A., Guo A.C., Liang K., Vazquez-Fresno R. et al. HMDB 4.0: the human metabolome database for 2018. Nucleic Acids Res. 2018;46(D1):D608-D617. https://doi.org/10.1093/nar/gkx1089.Wishart D.S., Feunang Y.D., Marcu A., Guo A.C., Liang K., Vazquez-Fresno R. et al. HMDB 4.0: the human metabolome database for 2018. Nucleic Acids Res. 2018;46(D1):D608-D617. https://doi.org/10.1093/nar/gkx1089.Oleskin A.V., Shenderov B.A. Neuromodulatory effects and targets of the SCFAs and gasotransmitters produced by the human symbiotic microbiota. Microb Ecol Health Dis. 2016;27:30971. https://doi.org/10.3402/mehd.v27.30971.Oleskin A.V., Shenderov B.A. Neuromodulatory effects and targets of the SCFAs and gasotransmitters produced by the human symbiotic microbiota. Microb Ecol Health Dis. 2016;27:30971. https://doi.org/10.3402/mehd.v27.30971.Nankova B.B., Agarwal R., MacFabe D.F., La Gamma E.F. Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells -possible relevance to autism spectrum disorders. PloS ONE. 2014;9(8):e103740. https://doi.org/10.1371/journal.pone.0103740.Nankova B.B., Agarwal R., MacFabe D.F., La Gamma E.F. Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells -possible relevance to autism spectrum disorders. PloS ONE. 2014;9(8):e103740. https://doi.org/10.1371/journal.pone.0103740.Hill C., Guarner F., Reid G., Gibson G.R., Merenstein D.J., Pot B. et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-514. https://doi.org/10.1038/nrgastro.2014.66.Hill C., Guarner F., Reid G., Gibson G.R., Merenstein D.J., Pot B. et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-514. https://doi.org/10.1038/nrgastro.2014.66.Gibson G.R., Roberfroid M.B. Dietary modulation of the human colonic microbiota: Introducing the concept of prebiotics. J Nutr. 1995;125(6):1401-1412. https://doi.org/10.1093/jn/125.6.1401.Gibson G.R., Roberfroid M.B. Dietary modulation of the human colonic microbiota: Introducing the concept of prebiotics. J Nutr. 1995;125(6):1401-1412. https://doi.org/10.1093/jn/125.6.1401.Gibson G.R., Hutkins R., Sanders M.E., Prescott S.L., Reimer R.A., Salminen S.J. et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14(8):491-502. https://doi.org/10.1038/nrgastro.2017.75.Gibson G.R., Hutkins R., Sanders M.E., Prescott S.L., Reimer R.A., Salminen S.J. et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14(8):491-502. https://doi.org/10.1038/nrgastro.2017.75.Phillips J.G.P. The treatment of melancholia by the lactic acid bacillus. J Ment Sci. 1910;56(234):422-430. https://doi.org/10.1192/bjp.56.234.422.Phillips J.G.P. The treatment of melancholia by the lactic acid bacillus. J Ment Sci. 1910;56(234):422-430. https://doi.org/10.1192/bjp.56.234.422.Logan A.C., Katzman M. Major depressive disorder: probiotics may be an adjuvant therapy. Med Hypotheses. 2005;64(3):533-538. https://doi.org/10.1016/j.mehy.2004.08.019.Logan A.C., Katzman M. Major depressive disorder: probiotics may be an adjuvant therapy. Med Hypotheses. 2005;64(3):533-538. https://doi.org/10.1016/j.mehy.2004.08.019.Burnet P.W.J., Cowen P.J. Psychobiotics highlight the pathways to happiness. Biol Psychiatry. 2013;74(10):708-709. https://doi.org/10.1016/j.bio-psych.2013.08.002.Burnet P.W.J., Cowen P.J. Psychobiotics highlight the pathways to happiness. Biol Psychiatry. 2013;74(10):708-709. https://doi.org/10.1016/j.bio-psych.2013.08.002.Matcovitch-Natan O., Winter D.R., Giladi A., Vargas Aguilar S., Spinrad A., Sarrazin S. et al. Microglia development follows a stepwise program to regulate brain homeostasis. Science. 2016;353(6301):aad8670. https://doi.org/10.1126/science.aad8670.Matcovitch-Natan O., Winter D.R., Giladi A., Vargas Aguilar S., Spinrad A., Sarrazin S. et al. Microglia development follows a stepwise program to regulate brain homeostasis. Science. 2016;353(6301):aad8670. https://doi.org/10.1126/science.aad8670.Bambury A., Sandhu K., Cryan J.F., Dinan T.G. Finding the needle in the haystack: Systematic identification of psychobiotics. Br J Pharmacol. 2018;175(24):4430-4438. https://doi.org/10.1111/bph.14127.Bambury A., Sandhu K., Cryan J.F., Dinan T.G. Finding the needle in the haystack: Systematic identification of psychobiotics. Br J Pharmacol. 2018;175(24):4430-4438. https://doi.org/10.1111/bph.14127.Forsythe P., Sudo N., Dinan T., Taylor V.H., Bienenstock J. Mood and gut feelings. Brain Behav Immun. 2010;24(1):9-16. https://doi.org/10.1016/j.bbi.2009.05.058.Forsythe P., Sudo N., Dinan T., Taylor V.H., Bienenstock J. Mood and gut feelings. Brain Behav Immun. 2010;24(1):9-16. https://doi.org/10.1016/j.bbi.2009.05.058.Mayer E.A. The neurobiology of stress and gastrointestinal disease. Gut. 2000;47(6):861-869. https://doi.org/10.1136/gut.47.6.861.Mayer E.A. The neurobiology of stress and gastrointestinal disease. Gut. 2000;47(6):861-869. https://doi.org/10.1136/gut.47.6.861.Eyre H., Baune B.T. Neuroplastic changes in depression: A role for the immune system. Psychoneuroendocrinology. 2012;37(9):1397-1416. https://doi.org/10.1016/j.psyneuen.2012.03.019.Eyre H., Baune B.T. Neuroplastic changes in depression: A role for the immune system. Psychoneuroendocrinology. 2012;37(9):1397-1416. https://doi.org/10.1016/j.psyneuen.2012.03.019.Gareau M.G., Jury J., MacQueen G., Sherman P.M., Perdue M.H. Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation. Gut. 2007;56(11):1522-1528. https://doi.org/10.1136/gut.2006.117176.Gareau M.G., Jury J., MacQueen G., Sherman P.M., Perdue M.H. Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation. Gut. 2007;56(11):1522-1528. https://doi.org/10.1136/gut.2006.117176.Foster J.A., McVey Neufeld K.-A. Gut-brain axis: How the microbiome influences anxiety and depression. Trends Neurosci. 2013;36(5):305-312. https://doi.org/10.1016/j.tins.2013.01.005.Foster J.A., McVey Neufeld K.-A. Gut-brain axis: How the microbiome influences anxiety and depression. Trends Neurosci. 2013;36(5):305-312. https://doi.org/10.1016/j.tins.2013.01.005.Amaral F.A., Sachs D., Costa V.V., Fagundes C.T., Cisalpino D., Cunha T.M. et al. Commensal microbiota is fundamental for the development of inflammatory pain. Proc Natl Acad Sci U S A. 2008;105(6):2193-2197. https://doi.org/10.1073/pnas.0711891105.Amaral F.A., Sachs D., Costa V.V., Fagundes C.T., Cisalpino D., Cunha T.M. et al. Commensal microbiota is fundamental for the development of inflammatory pain. Proc Natl Acad Sci U S A. 2008;105(6):2193-2197. https://doi.org/10.1073/pnas.0711891105.Lv F., Chen S., Wang L., Jiang R., Tian H., Li J. et al. The role of microbiota in the pathogenesis of schizophrenia and major depressive disorder and the possibility of targeting microbiota as a treatment option. Oncotarget. 2017;8(59):100899-100907. https://doi.org/10.18632/oncotarget.21284.Lv F., Chen S., Wang L., Jiang R., Tian H., Li J. et al. The role of microbiota in the pathogenesis of schizophrenia and major depressive disorder and the possibility of targeting microbiota as a treatment option. Oncotarget. 2017;8(59):100899-100907. https://doi.org/10.18632/oncotarget.21284.Han A., Sung Y.-B., Chung S.-Y., Kwon M.-S. Possible additional antidepressant-like mechanism of sodium butyrate: targeting the hippocampus. Neuropharmacology. 2014;81:292-302. https://doi.org/10.1016/j.neuro-pharm.2014.02.017.Han A., Sung Y.-B., Chung S.-Y., Kwon M.-S. Possible additional antidepressant-like mechanism of sodium butyrate: targeting the hippocampus. Neuropharmacology. 2014;81:292-302. https://doi.org/10.1016/j.neuro-pharm.2014.02.017.Surawicz C.M., Elmer G.W., Speelman P., McFarland L.V., Chinn J., Van Belle G. Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study. Gastroenterology. 1989;96(4):981-988. https://doi.org/10.1016/0016-5085(89)91613-2.Surawicz C.M., Elmer G.W., Speelman P., McFarland L.V., Chinn J., Van Belle G. Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study. Gastroenterology. 1989;96(4):981-988. https://doi.org/10.1016/0016-5085(89)91613-2.Chalmers J.A., Quintana D.S., Abbott M.J.-A., Kemp A.H. Anxiety disorders are associated with reduced heart rate variability: a meta-analysis. Front Psychiatry. 2014;5:80. https://doi.org/10.3389/fpsyt.2014.00080.Chalmers J.A., Quintana D.S., Abbott M.J.-A., Kemp A.H. Anxiety disorders are associated with reduced heart rate variability: a meta-analysis. Front Psychiatry. 2014;5:80. https://doi.org/10.3389/fpsyt.2014.00080.Clamor A., Lincoln T.M., Thayer J.F., Koenig J. Resting vagal activity in schizophrenia: meta-analysis of heart rate variability as a potential endophenotype. Br J Psychiatry. 2016;208(1):9-16. https://doi.org/10.1192/bjp.bp.114.160762.Clamor A., Lincoln T.M., Thayer J.F., Koenig J. Resting vagal activity in schizophrenia: meta-analysis of heart rate variability as a potential endophenotype. Br J Psychiatry. 2016;208(1):9-16. https://doi.org/10.1192/bjp.bp.114.160762.Akkasheh G., Kashani-Poor Z., Tajabadi-Ebrahimi M., Jafari P., Akbari H., Taghizadeh M. et al. Clinical and metabolic response to probiotic administration in patients with major depressive disorder: a randomized, doubleblind, placebo-controlled trial. Nutrition. 2016;32(3):315-320. https://doi.org/10.1016/j.nut.2015.09.003.Akkasheh G., Kashani-Poor Z., Tajabadi-Ebrahimi M., Jafari P., Akbari H., Taghizadeh M. et al. Clinical and metabolic response to probiotic administration in patients with major depressive disorder: a randomized, doubleblind, placebo-controlled trial. Nutrition. 2016;32(3):315-320. https://doi.org/10.1016/j.nut.2015.09.003.Pinto-Sanchez M.I., Hall G.B., Ghajar K., Nardelli A., Bolino C., Lau J.T. et al. Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome. Gastroenterology. 2017;153(2):448-459.e8. https://doi.org/10.1053/j.gastro.2017.05.003.Pinto-Sanchez M.I., Hall G.B., Ghajar K., Nardelli A., Bolino C., Lau J.T. et al. Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome. Gastroenterology. 2017;153(2):448-459.e8. https://doi.org/10.1053/j.gastro.2017.05.003.Bravo J.A., Forsythe P., Chew M.V., Escaravage E., Savignac H.M., Dinan T.G. et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011;108(38):16050-16055. https://doi.org/10.1073/pnas.1102999108.Bravo J.A., Forsythe P., Chew M.V., Escaravage E., Savignac H.M., Dinan T.G. et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011;108(38):16050-16055. https://doi.org/10.1073/pnas.1102999108.Dickerson F.B., Stallings C., Origoni A., Katsafanas E., Savage C.L.G., Schweinfurth L.A.B. et al. Effect of probiotic supplementation on schizophrenia symptoms and association with gastrointestinal functioning: a randomized, placebo-controlled trial. Prim Care Companion CNS Disord. 2014;16(1):PCC.13m01579. https://doi.org/10.4088/PCC.13m01579.Dickerson F.B., Stallings C., Origoni A., Katsafanas E., Savage C.L.G., Schweinfurth L.A.B. et al. Effect of probiotic supplementation on schizophrenia symptoms and association with gastrointestinal functioning: a randomized, placebo-controlled trial. Prim Care Companion CNS Disord. 2014;16(1):PCC.13m01579. https://doi.org/10.4088/PCC.13m01579.Kelly J.R., Allen A.P., Temko A., Hutch W., Kennedy P.J., Farid N. et al. Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects. Brain Behav Immun. 2017;61:50-59. https://doi.org/10.1016/j.bbi.2016.11.018.Kelly J.R., Allen A.P., Temko A., Hutch W., Kennedy P.J., Farid N. et al. Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects. Brain Behav Immun. 2017;61:50-59. https://doi.org/10.1016/j.bbi.2016.11.018.Benton D., Williams C., Brown A. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur J Clin Nutr. 2007;61(3):355-361. https://doi.org/10.1038/sj.ejcn.1602546.Benton D., Williams C., Brown A. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur J Clin Nutr. 2007;61(3):355-361. https://doi.org/10.1038/sj.ejcn.1602546.Дармов И.В., Чичерин И.Ю., Ердякова А.С., Погорельский И.П., Лундовских И.А. Сравнительная оценка выживаемости микроорганизмов пробиотиков в составе коммерческих препаратов в условиях in vitro. Гастроэнтерология. 2011;(9):96-101. Режим доступа: https://cyberleninka.ru/article/n/sravnitelnaya-otsenka-vyzhivaemosti-mikroorganizmov-probiotikov-v-sostave-kommercheskih-preparatov-v-usloviyah-in-vitro.Darmov I.V., Chicherin I.Yu., Erdyakova A.S., Pogorelskiy I.P., Lundovskikh I.A. Comparative assessment of in vitro survival of probiotic microorganisms as part of commercial drugs. Gastroenterology. 2011;(9):96-101. (In Russ.) Available at: https://cyberleninka.ru/article/n/sravnitelnaya-otsenka-vyzhivaemosti-mikroorganizmov-probiotikov-v-sostave-kommercheskih-preparatov-v-usloviyah-in-vitro.

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