Journal of microbiology, epidemiology and immunobiologyJournal of microbiology, epidemiology and immunobiologyЖурнал микробиологии, эпидемиологии и иммунобиологии0372-93112686-7613Central Research Institute for Epidemiology133110.36233/0372-9311-356nkhjezREVIEWSОБЗОРЫReview ArticleGut microbiota and carcinogenesis: actual aspectsКишечная микробиота и канцерогенез: актуальные аспектыhttps://orcid.org/0000-0002-4433-71106495-7412PoveshchenkoAleksandr F.ПовещенкоАлександр Федорович
Russian Federation

D. Sci. (Med.), Head, Department of experimental lymphology and laboratory of physiology of the protective system

д.м.н., профессор, зав. отделом экспериментальной лимфологии и лаб. физиологии протективной системы

poveshchenkoa200@mail.ruhttps://orcid.org/0000-0002-0380-92736555-5690CherkasValeria N.ЧеркасВалерия Николаевна
Russian Federation

Cand. Sci. (Vet.), researcher, Laboratory of physiology of protective system

к.вет.н., н.с. лаб. физиологии протективной системы

valeriya_korol@mail.ruhttps://orcid.org/0000-0002-4741-66748615-2370KabakovAleksey V.КабаковАлексей Васильевич
Russian Federation

Cand. Sci. (Med.), researcher, Laboratory of physiology of protective system

к.м.н., н.с. лаб. физиологии протективной системы

Doctor03-85@ngs.ruhttps://orcid.org/0000-0003-3947-40384565-7180KazakovOleg V.КазаковОлег Васильевич
Russian Federation

Cand. Sci. (Biol.), leading researcher, Laboratory of physiology of protective system

к.б.н., в.н.с. лаб. физиологии протективной системы

kazakoff_oleg@mail.ruResearch Institute of Clinical and Experimental Lymphology — Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of SciencesНИИ клинической и экспериментальной лимфологии — филиал ФИЦ «Институт цитологии и генетики СО РАН»11072023100324726011112022Copyright ©; 2023, Poveshchenko A.F., Cherkas V.N., Kabakov A.V., Kazakov O.V.Copyright ©; 2023, Повещенко А.Ф., Черкас В.Н., Кабаков А.В., Казаков О.В.2023Poveshchenko A.F., Cherkas V.N., Kabakov A.V., Kazakov O.V.Повещенко А.Ф., Черкас В.Н., Кабаков А.В., Казаков О.В.https://creativecommons.org/licenses/by/4.0https://microbiol.crie.ru/jour/article/view/1331

The microbiota, together with the host, form a symbiotic relationship in which the microbiota plays a key role in maintaining the homeostasis of the human body, performing a number of significant functions such as energy metabolism, maturation and maintenance of the immune system, vitamin synthesis, regulation of bile acid reabsorption in the intestine, and much more. Scientific research in recent years has made a significant contribution to understanding the complex relationship between the microbiota and a range of human pathologies, including malignant neoplasms.

The review considers the mechanisms of the possible influence of bacteria on the development and progression of cancer with an emphasis on the procarcinogenic properties of the microbiota. The most important factor in the mechanism of influence of the microbiota on carcinogenesis are toxins produced by microorganisms that induce direct damage to host cell DNA, causing DNA mutations, disruption of its exact replication, and also provoke an imbalance in the proliferation and apoptosis of host cells, their rapid aging and oncogenesis. The probable mechanisms of participation of microorganisms in the development of cancer through the activation of TLRs and NLRs receptors, which have a tumor-activating effect, are considered. A brief review is given on the mechanisms of carcinogenesis associated with the metabolic activity of the microbiota due to the processes of regulation of the production of secondary bile acids, activation of pro-carcinogenic compounds: phenols, ethanol, sulfides, ammonia, nitrosamines. The influence of the microbiota on the metabolism of sex hormones and the development of hormone-dependent cancers mediated by the mechanisms of enterohepatic circulation and estrogen deconjugation is described.

The study of the carcinogenic mechanisms of action of the microbiota in the host organism opens up prospects for the development of new successful personalized approaches to the diagnosis, treatment, and prevention of cancer. Changing the composition of the microbiota should become a way to fight cancer, along with surgical treatment, chemotherapy, radiation therapy, targeted therapy and immunotherapy.

Микробиота совместно с хозяином формируют симбиотические отношения, в которых микробиота играет ключевую роль в поддержании гомеостаза организма человека, выполняя значимые функции: энергетический обмен, созревание и поддержание иммунной системы, синтез витаминов, регуляцию обратного всасывания в кишечнике желчных кислот и др. Научные исследования последних лет внесли значительный вклад в понимание сложной связи между микробиотой и рядом патологий человека, включая злокачественные новообразования.

В обзоре рассмотрены механизмы возможного влияния бактерий на развитие и прогрессию рака с акцентом на проканцерогенные свойства микробиоты. Отражено, что важнейшим фактором механизма влияния микробиоты на канцерогенез являются токсины, продуцируемые микроорганизмами, которые индуцируют прямые реакции повреждения ДНК клеток хозяина, вызывая мутации ДНК, нарушения её точной репликации, а также провоцируют нарушение баланса пролиферации и апоптоза клеток хозяина, их быстрое старение и онкогенез. Рассмотрены вероятные механизмы участия микроорганизмов в развитии рака через активацию TLRs и NLRs рецепторов, обладающих опухоль-активирующим эффектом. Приводится краткий обзор механизмов канцерогенеза, связанных с метаболической активностью микробиоты за счёт процессов регуляции выработки вторичных желчных кислот, активации проканцерогенных соединений: фенолов, этанола, сульфидов, аммиака, нитрозаминов. Описано влияние микробиоты на метаболизм половых гормонов и развитие гормонозависимых видов рака, опосредованных механизмами энтерогепатической циркуляции и деконъюгации эстрогенов.

Изучение канцерогенных механизмов действия микробиоты в организме хозяина открывает перспективы разработки новых успешных персонализированных подходов к вопросу диагностики, лечения и профилактики рака. Изменение состава микробиоты должно стать способом борьбы с онкологическими заболеваниями, наряду с хирургическим лечением, химиотерапией, лучевой терапией, таргетной терапией и иммунотерапией.

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