mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-PON-2962mimmun-2962Research ArticleОБЗОРЫREVIEWSПерспективы создания новых лечебно-профилактических средств на основе симбиотических штаммов бактерий для коррекции нарушений иммунной регуляции, опосредованной кишечной микробиотой при COVID-19Prospectives of novel therapeutic and prophylactic medications based on symbiotic bacterial strains for correction of immune disorders mediated by intestinal microbiota in COVID-19БухаринО. В.BukharinO. V.

Бухарин О.В. – д.м.н., академик РАН, главный научный сотрудник лаборатории биомониторинга и молекулярной генетики Института клеточного и внутриклеточного симбиоза Уральского отделения Российской академии наук – обособленное структурное подразделение 

г. Оренбург

Bukharin O.V., PhD, MD (Medicine), Full Member, Russian Academy of Sciences, Chief Researcher, Head, Laboratory of Biomonitoring and Molecular Genetics, Institute of Cellular and Intracellular Symbiosis 

Orenburg

ПеруноваН. Б.PerunovaN. B.

Перунова Н.Б. – д.м.н., профессор РАН, заместитель директора по научной работе, ведущий научный сотрудник лаборатории биомониторинга и молекулярной генетики Института клеточного и внутриклеточного симбиоза Уральского отделения Российской академии наук – обособленное структурное подразделение; главный научный сотрудник лаборатории микробиома, регенеративной медицины и клеточных технологий Университетского научно-исследовательского института медицинских биотехнологий и биомедицины 

г. Оренбург;625023, г. Тюмень, ул. Одесская, 54.

Perunova N.B., PhD, MD (Medicine), Professor, Russian Academy of Sciences, Deputy Director for Research, Leading Researcher, Laboratory of Biomonitoring and Molecular Genetics, Institute of Cellular and Intracellular Symbiosis; Chief Researcher, Laboratory of Microbiome, Regenerative Medicine and Cell Technologies, University Research Institute of Medical Biotechnologies and Biomedicine 

Orenburg;54 Odesskaya St Tyumen 625023

ТимохинаТ. Х.TimokhinaT. Kh.

Тимохина Т.Х. – д.б.н., доцент, заведующая кафедрой микробиологии Института фармации 

625023, г. Тюмень, ул. Одесская, 54.

Timokhina T.Kh., PhD, MD (Biology), Associate Professor, Head, Department of Microbiology, Institute of Pharmacy 

54 Odesskaya St Tyumen 625023

КостоломоваЕ. Г.KostolomovaE. G.

Костоломова Е.Г. – к.б.н., доцент кафедры микробиологии Института фармации; научный сотрудник лаборатории геномики, протеомики и метаболомики Университетского научноисследовательского института медицинских биотехнологий и биомедицины

625023, г. Тюмень, ул. Одесская, 54.

Kostolomova E.G., PhD (Biology), Associate Professor, Department of Microbiology, Institute of Pharmacy; Researcher, Laboratory of Genomics, Proteomics and Metabolomics, University Research Institute of Medical Biotechnologies and Biomedicine 

54 Odesskaya St Tyumen 625023

lenakost@mail.ruПаромоваЯ. И.ParomovaYa. I.

Паромова Я.И. – к.б.н., доцент кафедры микробиологии 

625023, г. Тюмень, ул. Одесская, 54.

Paromova Ya.I., PhD (Biology), Associate Professor, Department of Microbiology, Institute of Pharmacy 

54 Odesskaya St Tyumen 625023

ИвановаЕ. В.IvanovaE. V.

Иванова Е.В. – д.м.н., доцент, ведущий научный сотрудник с исполнением обязанностей заведующего лабораторией инфекционной симбиологии, Институт клеточного и внутриклеточного симбиоза Уральского отделения Российской академии наук – обособленное структурное подразделение 

г. Оренбург

Ivanova E.V., PhD (Medicine), Associate Professor, Leading Researcher, Head, Laboratory of Infectious Symbiology, Institute of Cellular and Intracellular Symbiosis 

Orenburg

ПолянскихЕ. Д.PolyanskihE. D.

Полянских Е.Д. – студент Института материнства и детства 

625023, г. Тюмень, ул. Одесская, 54.

Polyanskih E.D., Student, Institute of Maternity and Childhood 

54 Odesskaya St Tyumen 625023

МарковА. А.MarkovA. A.

Марков А.А. – к.м.н., ведущий научный сотрудник лаборатории геномики, протеомики, метаболомики, директор Университетского научно-исследовательского института медицинских биотехнологий и биомедицины; доцент кафедры медицинской профилактики и реабилитации Института общественного здоровья и цифровой медицины 

625023, г. Тюмень, ул. Одесская, 54.

Markov A.A., PhD (Medicine), Leading Researcher, Laboratory of Genomics, Proteomics, Metabolomics, Director, University Research Institute of Medical Biotechnologies and Biomedicine; Associate Professor, Department of Medical Prevention and Rehabilitation, Institute of Public Health and Digital Medicine 

54 Odesskaya St Tyumen 625023

ФГБУН «Оренбургский федеральный исследовательский центр» Уральского отделения Российской академии наукРоссияOrenburg Federal Research Centre, Ural Branch, Russian Academy of SciencesRussian FederationФГБУН «Оренбургский федеральный исследовательский центр» Уральского отделения Российской академии наук; ФГБОУ ВО «Тюменский государственный медицинский университет» Министерства здравоохранения РФРоссияOrenburg Federal Research Centre, Ural Branch, Russian Academy of Sciences; Tyumen State Medical UniversityRussian FederationФГБОУ ВО «Тюменский государственный медицинский университет» Министерства здравоохранения РФРоссияTyumen State Medical UniversityRussian Federation202515102025275961972Copyright © Бухарин О.В., Перунова Н.Б., Тимохина Т.Х., Костоломова Е.Г., Паромова Я.И., Иванова Е.В., Полянских Е.Д., Марков А.А., 20252025Бухарин О.В., Перунова Н.Б., Тимохина Т.Х., Костоломова Е.Г., Паромова Я.И., Иванова Е.В., Полянских Е.Д., Марков А.А.Bukharin O.V., Perunova N.B., Timokhina T.K., Kostolomova E.G., Paromova Y.I., Ivanova E.V., Polyanskih E.D., Markov A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2962

Современные исследования роли кишечной микробиоты у животных и человека показывают, что микроорганизмы являются важным фактором, определяющим здоровье хозяина, и участвуют в патогенезе различных инфекционных и неинфекционных заболеваний. В настоящее время активно исследуются механизмы формирования функциональной оси «кишечник – легкие» при новой коронавирусной инфекции COVID-19, где желудочно-кишечный тракт может являться входными воротами инфекции, указывая на вовлечение кишечной микробиоты в инфекционный процесс. С одной стороны, изменение микробиоты пациентов (дисбиоз), инфицированных вирусом SARS-CoV-2, является одним из факторов развития вторичной бактериальной инфекции, сепсиса, системного воспаления и полиорганной недостаточности. С другой стороны, нарушение микробиоты кишечника способствует развитию тяжелого течения и летального исхода у пациентов из-за двунаправленной связи кишечной микробиоты через систему иммунитета посредством цитокинов. Показана связь степени тяжести COVID-19 у пациентов с уровнем цитокинов и выявлением в кишечном биотопе определенных видов «провоспалительных» или «противовоспалительных» бактерий. Иммунологические нарушения у пациентов с COVID-19 также опосредованы изменением профиля метаболома на фоне дисбиотических нарушений микробиоты. Связь между составом микробиоты кишечника, уровнями цитокинов и воспалительными маркерами позволяет предположить, что микробиом кишечника влияет на развитие и течение коронавирусной инфекции, а «симбиотический потенциал» нормобиоты может быть использован для разработки мер профилактики и реабилитации пациентов. Этому может способствовать развитие исследований в направлении проблемы симбиоза человека и микробиоты. Ряд ключевых механизмов изучения интеграции бифидобактерий и лактобацилл с хозяином, опосредованные системой иммунитета, гормонов и нейромедиаторов, открывают новые перспективы для медицины, включая получение новых пробиотических штаммов различной целевой установки для лечебно-профилактической коррекции нарушенных функций организма. Изучение микросимбиоценоза, как одного из векторов ассоциативного симбиоза, позволило разработать метод межмикробного распознавания «свой-чужой», где в качестве тестовой распознающей культуры используются бифидобактерии, т. к. для «своих» штаммов характерен синергизм (поддержка), тогда как при встрече с «чужой клеткой» – антагонизм. Именно этот фундаментальный механизм можно использовать при отборе «своих» для хозяина штаммов, пригодных для создания пробиотической композиции.

Recent studies on the role of intestinal microbiota in animals and humans show that the microorganisms are an important determinant of host health, participating in the pathogenesis of various infectious and non-infectious diseases. Currently, the effects of functional gut-lung axis are being actively investigated in the new coronavirus (COVID-19) infection. Gastrointestinal tract may be the point of entry for infection, suggesting involvement of intestinal microbiota in the infectious process. On the one hand, the changes in gut microbiota (dysbiosis) in SARS-CoV-2 patients may be among the factors contributing to development of secondary bacterial infection, sepsis, systemic inflammation and multi-organ failure. On the other hand, impaired gut microbiota contributes to severe clinical course and mortality in patients due to bidirectional coupling of the gut microbiota with immune system via cytokine network. The studies have shown a link between the severity of COVID-19 in patients, cytokine levels, and presence of distinct types of pro- and anti-inflammatory bacteria in the intestinal biotope. Immune abnormalities in COVID-19 patients are also mediated by altered metabolome profile associated with dysbiotic microbiota. The relations between gut microbiota composition, cytokine levels and inflammatory markers suggests that the gut microbiome may influence the progression of coronavirus infection. Therefore, the “symbiotic potential” of normobiotic microbiota may be used to develop prevention and rehabilitation strategies for the patients. This approach may be facilitated by the studies of human-microbiota symbiosis. A number of key mechanisms for studying the integration of Bifidobacteria and Lactobacilli with the host mediated by the immune system, hormones and neurotransmitters are opening new perspectives for medicine, including development of differently targeted probiotic strains for therapeutic and preventative correction of impaired functions within the organism. The studies of microsymbiocenosis, being a vector of associative symbiosis have enabled a technical approach for intermicrobial “friend or foe identification”, where bifidobacteria are used as a diagnostic culture, since “friendly” strains are characterised by synergism (support). By contrary, encountering the “foreign cells” leads to antagonism. This fundamental mechanism may be used for choosing the “host-friendly” bacteria strains eligible for design of a probiotic compositions.

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