oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2025-24-1-150-163oncotomsk-3456Research ArticleОБЗОРЫREVIEWSПробиотики против патогенных бактерий и ракаProbiotics against pathogenic bacteria and cancerБелявскаяВ. А.BelyavskayaV. A.

Белявская Валентина Александровна - доктор биологических наук, профессор, ведущий научный сотрудник.

630559, р. п. Кольцово, Новосибирск

Author ID (Scopus) 6701653852

Valentina A. Belyavskaya - DSc, Professor, Leading Researcher, State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor.

Koltsovo, Novosibirsk, 630559

Author ID (Scopus) 6701653852

https://orcid.org/0000-0003-1526-9013ЧердынцеваН. В.CherdyntsevaN. V.

Чердынцева Надежда Викторовна - доктор биологических наук, профессор, член-корреспондент РАН, заведующая лабораторией молекулярной онкологии и иммунологии, заместитель директора, НИИ онкологии, Томский НИМЦ РАН; профессор кафедры природных соединений, фармацевтики и медицинской химии, ФГАОУ ВО «ТГУ».

634009, Томск, пер. Кооперативный, 5; 634050, Томск, ул. Ленина, 36

Researcher ID (WOS) C-7943-2012, Author ID (Scopus) 6603911744

Nadezda V. Cherdyntseva - DSc, Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Laboratory of Molecular Oncology and Immunology, Deputy Director, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; Professor, Department of Natural Compounds, Pharmaceutics and Medical Chemistry, National Research Tomsk State University.

5, Kooperativny St., Tomsk, 634009; 36, Lenina St., Tomsk, 634050

Researcher ID (WOS) C-7943-2012, Author ID (Scopus) 6603911744

nvch@tnimc.ruhttps://orcid.org/0000-0002-0714-8927ЛитвяковН. В.LitviakovN. V.

Литвяков Николай Васильевич - доктор биологических наук, профессор РАН, заведующий лабораторией онковирусологии, НИИ онкологии, Томский НИМЦ РАН; научный сотрудник лаборатории генетических технологий центральной научно-исследовательской лаборатории, ФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава России.

634009, Томск, пер. Кооперативный, 5

Researcher ID (WOS) C-3263-2012, Author ID (Scopus) 6506850698

Nikolai V. Litviakov - DSc, Professor, Head of Viral Oncology Department, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; Researcher, Laboratory of Genetic Technologies of the Central Research Laboratory, Siberian State Medical University of the Ministry of Health of Russia.

5, Kooperativny St., Tomsk, 634009

Researcher ID (WOS) C-3263-2012, Author ID (Scopus) 6506850698

https://orcid.org/0000-0003-2060-4840ПономареваА. A.PonomaryovaA. A.

Пономарева Анастасия Алексеевна - кандидат биологических наук, научный сотрудник лаборатории молекулярной онкологии и иммунологии.

634009, Томск, пер. Кооперативный, 5

Researcher ID (WOS) D-8734-2012, Author ID (Scopus) 37116096000

Anastasia A. Ponomaryova - PhD, Researcher, Laboratory of Molecular Oncology and Immunology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences.

5, Kooperativny St., Tomsk, 634009

Researcher ID (WOS) D-8734-2012, Author ID (Scopus) 37116096000

https://orcid.org/0000-0002-6104-4782УдутЕ. В.UdutE. V.

Удут Елена Владимировна - доктор медицинских наук, профессор, заведующая центральной научно-исследовательской лабораторией.

634050, Томск, Московский тракт, 2

Researcher ID (WOS) O-9807-2015, Author ID (Scopus) 6507329853

Elena V. Udut - DSc, Professor, Head of Central Research Laboratory, Siberian State Medical University of the Ministry of Health of Russia.

2, Moskovsky trakt, Tomsk, 634050

Researcher ID (WOS) O-9807-2015, Author ID (Scopus) 6507329853

ФБУН «Государственный научный центр вирусологии и биотехнологии “Вектор” Роспотребнадзора»РоссияState Research Center of Virology and Biotechnology “Vector”, RospotrebnadzorRussian FederationНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наук; ФГАОУ ВО «Национальный исследовательский Томский государственный университет»РоссияCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; National Research Tomsk State UniversityRussian FederationНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукРоссияCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesRussian FederationФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава РоссииРоссияSiberian State Medical University of the Ministry of Health of RussiaRussian Federation202518032025241150163Copyright © Белявская В.А., Чердынцева Н.В., Литвяков Н.В., Пономарева А.A., Удут Е.В., 20252025Белявская В.А., Чердынцева Н.В., Литвяков Н.В., Пономарева А.A., Удут Е.В.Belyavskaya V.A., Cherdyntseva N.V., Litviakov N.V., Ponomaryova A.A., Udut E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/3456

Введение. Обзор фокусируется на роли пробиотиков в качестве альтернативных агентов для профилактики и лечения рака. В связи с этим в настоящем обзоре мы обсуждаем альтернативные биотерапевтические препараты для лечения рака, которые применяются в лабораторных условиях, in vivo и клинических исследованиях. Эти препараты включают живые или мертвые пробиотики и их метаболиты, в частности, короткоцепочечные жирные кислоты, ингибирующие соединения белка, полисахариды, нуклеиновые кислоты и феррихром. В обзоре представлены имеющиеся данные о взаимосвязи микробиома с развитием рака шейки матки, рака молочной железы и колоректального рака, а также данные о применении пробиотиков для профилактики и лечения рака. Материал и методы. Нами был проведен анализ современной литературы с использованием баз данных Pubmed и eLibrary. Из 140 статей на эту тему в обзор были включено 57. Результаты. Показано, что микробиом играет важную роль в поддержании клеточной и генетической стабильности в организме. Микробиом действует как защитный барьер от инфекционных агентов и при развитии различных патологических процессов, включая рак. Микробиом использует несколько стратегий для нейтрализации канцерогенных веществ. Предварительные клинические испытания показали, что пробиотики могут быть использованы для профилактики рака и могут влиять на эффективность противоопухолевой терапии. Однако для подтверждения данного предположения необходимы дальнейшие исследования. Современные противоопухолевые препараты часто имеют существенные недостатки, включая негативное влияние на качество жизни пациентов, развитие лекарственной устойчивости и высокую стоимость. Заключение. На эффективность пробиотической терапии влияют несколько факторов, таких как конкретный используемый штамм бактерий или грибков, применяемая дозировка, продолжительность лечения. В настоящем обзоре делается вывод о необходимости дальнейших клинических испытаний для подтверждения важной роли пробиотиков для профилактики и лечения рака. Необходимы более масштабные исследования для оценки как краткосрочных, так и долгосрочных эффектов пробиотиков, разработка стандартизированных методик. Применение таких подходов позволит снизить вероятность возникновения побочных эффектов и найти способ безопасного и эффективного применения пробиотиков в клинической практике.

This review focuses on the role of probiotics as alternative prevention and treatment of cancer. In this regard, we discuss the alternative cancer biotherapeutic drugs including live or dead probiotics and their metabolites, such as short chain fatty acids, inhibitory compounds of protein, polysaccharide, nucleic acid and ferrichrome in vitro, in vivo and clinical studies. We also summarize the available data on the relationship between the development of cervical, breast and colorectal cancers, and microbiome, as well as data about the potential of probiotics as an alternative approach to cancer prevention and treatment. Material and methods. A literature search was conducted using the Pubmed and eLibrary databases. Of 140 publications, the review included 57 studies. Results. the microbiome plays a crucial role in maintaining cellular and genetic stability within the body. it acts as a defense mechanism against infectious agents and various pathological processes including, cancers. The microbiome employs several strategies to neutralize carcinogenic agents. Preliminary clinical trials have yielded promising results, suggesting that probiotics may contribute to cancer prevention and enhance both the safety and efficacy of cancer treatment. However, further research is needed to confirm this suggestion. Current anticancer drugs often have significant drawbacks, including negative impact on patients’ quality of life, development of drug resistance, and high cost. Conclusion. The effectiveness of probiotic therapies appears to be influenced by several factors, such as the specific bacterial or fungal strain used, the dosage administered, and the duration of treatment. The review emphasizes the need for further rigorous clinical trials to validate the significant role of probiotics in cancer prevention and treatment. While existing research indicates promising results from probiotic treatments primarily in controlled settings, more extensive studies are required to assess both short-and long-term effects and establish standardized methodologies. This will help minimize potential side effects and find the way for the safe and effective application of probiotics as a medical intervention.

микробиомпробиотикирак молочной железыколоректальный ракгинекологический ракпрофилактика и лечение ракаmicrobiomeprobioticsbreast and colon cancergynecological cancerscancer prevention and treatmentРабота поддержана грантом Минобрнауки РФ № 075-15-2021-1073.The study was supported by the grant of the Ministry of Science and Higher Education of the Russian Federation No. 075-15-2021-1073.ReferencesSummer M., Ali S., Fiaz U., Tahir H.M., Ijaz M., Mumtaz S., Mushtaq R., Khan R., Shahzad H., Fiaz H. Therapeutic and immunomodulatory role of probiotics in breast cancer: A mechanistic review. Arch Microbiol. 2023; 205(8): 296. doi: 10.1007/s00203-023-03632-7.Summer M., Ali S., Fiaz U., Tahir H.M., Ijaz M., Mumtaz S., Mushtaq R., Khan R., Shahzad H., Fiaz H. Therapeutic and immunomodulatory role of probiotics in breast cancer: A mechanistic review. Arch Microbiol. 2023; 205(8): 296. doi: 10.1007/s00203-023-03632-7.Yan F., Polk D.B. Probiotics and Probiotic-Derived Functional Factors-Mechanistic Insights Into Applications for Intestinal Homeostasis. Front Immunol. 2020; 11. doi: 10.3389/fimmu.2020.01428.Yan F., Polk D.B. Probiotics and Probiotic-Derived Functional Factors-Mechanistic Insights Into Applications for Intestinal Homeostasis. Front Immunol. 2020; 11. doi: 10.3389/fimmu.2020.01428.Huang R., Liu Z., Sun T., Zhu L. Cervicovaginal microbiome, high-risk HPV infection and cervical cancer: Mechanisms and therapeutic potential. Microbiol Res. 2024; 287. doi: 10.1016/j.micres.2024.127857.Huang R., Liu Z., Sun T., Zhu L. Cervicovaginal microbiome, high-risk HPV infection and cervical cancer: Mechanisms and therapeutic potential. Microbiol Res. 2024; 287. doi: 10.1016/j.micres.2024.127857.Kvakova M., Kamlarova A., Stofilova J., Benetinova V., Bertkova I. Probiotics and postbiotics in colorectal cancer: Prevention and complementary therapy. World J Gastroenterol. 2022; 28(27): 3370-82. doi: 10.3748/wjg.v28.i27.3370.Kvakova M., Kamlarova A., Stofilova J., Benetinova V., Bertkova I. Probiotics and postbiotics in colorectal cancer: Prevention and complementary therapy. World J Gastroenterol. 2022; 28(27): 3370-82. doi: 10.3748/wjg.v28.i27.3370.Singh A., Alexander S.G., Mariin S. Gut microbiome homeostasis and the future of probiotics in cancer immunotherapy. Front Immunol. 2023; 14. doi: 10.3389/fimmu.2023.1114499.Singh A., Alexander S.G., Mariin S. Gut microbiome homeostasis and the future of probiotics in cancer immunotherapy. Front Immunol. 2023; 14. doi: 10.3389/fimmu.2023.1114499.Singh D., Singh A., Kumar S. Probiotics: friend or foe to the human immune system. Bull Natl Res Cent. 2023; 47. doi.org/10.1186/s42269-023-01098-7.Singh D., Singh A., Kumar S. Probiotics: friend or foe to the human immune system. Bull Natl Res Cent. 2023; 47. doi.org/10.1186/s42269-023-01098-7.Dos Reis SA., da Conceicao L.L., SiqueiraN.P., Rosa D.D., da Silva LL., Peluzio M.D. Review of the mechanisms of probiotic actions in the prevention of colorectal cancer. Nutr Res. 2017; 37: 1-19. doi: 10.1016/j.nutres.2016.11.009.Dos Reis SA., da Conceicao L.L., SiqueiraN.P., Rosa D.D., da Silva LL., Peluzio M.D. Review of the mechanisms of probiotic actions in the prevention of colorectal cancer. Nutr Res. 2017; 37: 1-19. doi: 10.1016/j.nutres.2016.11.009.Miira A., Guliekin M., Burney Ellis L., Bizzarri N., Bowden S., Taumberger N., Bracic T., Vieira-Bapiisia P., Sehouli J., Kyrgiou M. Genital tract microbiota composition profiles and use of prebiotics and probiotics in gynaecological cancer prevention: review of the current evidence, the European Society of Gynaecological Oncology prevention committee statement. Lancet Microbe. 2024; 5(3): 291-300. doi: 10.1016/S2666-5247(23)00257-4.Miira A., Guliekin M., Burney Ellis L., Bizzarri N., Bowden S., Taumberger N., Bracic T., Vieira-Bapiisia P., Sehouli J., Kyrgiou M. Genital tract microbiota composition profiles and use of prebiotics and probiotics in gynaecological cancer prevention: review of the current evidence, the European Society of Gynaecological Oncology prevention committee statement. Lancet Microbe. 2024; 5(3): 291-300. doi: 10.1016/S2666-5247(23)00257-4.Mei Z., Li D. The role of probiotics in vaginal health. Front Cell Infect Microbiol. 2022; 12. doi: 10.3389/fcimb.2022.963868.Mei Z., Li D. The role of probiotics in vaginal health. Front Cell Infect Microbiol. 2022; 12. doi: 10.3389/fcimb.2022.963868.Zitvogel L., Daillere R., Roberti M.P., Routy B., Kroemer G. Anticancer effects of the microbiome and its products. Nat Rev Microbiol. 2017; 15(8): 465-78. doi: 10.1038/nrmicro.2017.44.Zitvogel L., Daillere R., Roberti M.P., Routy B., Kroemer G. Anticancer effects of the microbiome and its products. Nat Rev Microbiol. 2017; 15(8): 465-78. doi: 10.1038/nrmicro.2017.44.Pourmollaei S., Barzegari A., Farshbaf-Khalili A., Nouri M., Fattahi A., Shahnazi M., Dittrich R. Anticancer effect of bacteria on cervical cancer: Molecular aspects and therapeutic implications. Life Sci. 2020; 246. doi: 10.1016/j.lfs.2020.117413.Pourmollaei S., Barzegari A., Farshbaf-Khalili A., Nouri M., Fattahi A., Shahnazi M., Dittrich R. Anticancer effect of bacteria on cervical cancer: Molecular aspects and therapeutic implications. Life Sci. 2020; 246. doi: 10.1016/j.lfs.2020.117413.Piqué N., Berlanga M., Miñana-Galbis D. Health Benefits of Heat-Killed (Tyndallized) Probiotics: An Overview. Int J Mol Sci. 2019; 20(10). doi: 10.3390/ijms20102534.Piqué N., Berlanga M., Miñana-Galbis D. Health Benefits of Heat-Killed (Tyndallized) Probiotics: An Overview. Int J Mol Sci. 2019; 20(10). doi: 10.3390/ijms20102534.Chee W.J.Y., Chew S.Y., Than L.T.L. Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health. Microb Cell Fact. 2020; 19(1): 203. doi: 10.1186/s12934-020-01464-4.Chee W.J.Y., Chew S.Y., Than L.T.L. Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health. Microb Cell Fact. 2020; 19(1): 203. doi: 10.1186/s12934-020-01464-4.Liang K., Liu Q., Li P., Luo H., Wang H., Kong Q. Genetically engineered Salmonella Typhimurium: Recent advances in cancer therapy. Cancer Lett. 2019; 448: 168-81. doi: 10.1016/j.canlet.2019.01.037.Liang K., Liu Q., Li P., Luo H., Wang H., Kong Q. Genetically engineered Salmonella Typhimurium: Recent advances in cancer therapy. Cancer Lett. 2019; 448: 168-81. doi: 10.1016/j.canlet.2019.01.037.Landry B.P., Tabor J.J. Engineering Diagnostic and Therapeutic Gut Bacteria. Microbiol Spectr. 2017; 5(5). doi: 10.1128/microbiolspec.BAD-0020-2017.Landry B.P., Tabor J.J. Engineering Diagnostic and Therapeutic Gut Bacteria. Microbiol Spectr. 2017; 5(5). doi: 10.1128/microbiolspec.BAD-0020-2017.Komatsu A., Igimi S., Kawana K. Optimization of human papillomavirus (HPV) type 16 E7-expressing lactobacillus-based vaccine for induction of mucosal E7-specific IFNY-producing cells. Vaccine. 2018; 36(24): 3423-26. doi: 10.1016/j.vaccine.2018.05.009.Komatsu A., Igimi S., Kawana K. Optimization of human papillomavirus (HPV) type 16 E7-expressing lactobacillus-based vaccine for induction of mucosal E7-specific IFNY-producing cells. Vaccine. 2018; 36(24): 3423-26. doi: 10.1016/j.vaccine.2018.05.009.Cortes-Perez N.G., Azevedo V., Alcocer-González J.M., Rodriguez-Padilla C., Tamez-Guerra R.S., Corthier G., Gruss A., Langella P., Bermúdez-Humarán L.G. Cell-surface display of E7 antigen from human papillomavirus type-16 in Lactococcus lactis and in Lactobacillus plantarum using a new cell-wall anchor from lactobacilli. J Drug Target. 2005; 13(2): 89-98. doi: 10.1080/10611860400024219.Cortes-Perez N.G., Azevedo V., Alcocer-González J.M., Rodriguez-Padilla C., Tamez-Guerra R.S., Corthier G., Gruss A., Langella P., Bermúdez-Humarán L.G. Cell-surface display of E7 antigen from human papillomavirus type-16 in Lactococcus lactis and in Lactobacillus plantarum using a new cell-wall anchor from lactobacilli. J Drug Target. 2005; 13(2): 89-98. doi: 10.1080/10611860400024219.Чердынцева Н.В., Литвяков Н.В., Смольянинов Е.С., Белявская В.А., Масычева В.И. Модуляция противоопухолевой активности циклофосфана рекомбинантным пробиотиком субалином. Вопросы онкологии. 1997; 43(3): 313-16. EDN: TOXOZJ.Cherdyntseva N.V., Litviakov N.V., Smo-lianinov E.S., Beliavskaia V.A., Masycheva V.I. Modulation of the antitumor effect of cyclophosphamide by the recombinant probiotic subalin. Problems in Oncology. 1997; 43(3): 313-16. (in Russian). EDN: TOXOZJ.Kanmani P., Satish Kumar R., Yuvaraj N., Paari K.A., Pat-tukumar V., Arul V. Probiotics and its functionally valuable prod-ucts-a review. Crit Rev Food Sci Nutr. 2013; 53(6): 641-58. doi: 10.1080/10408398.2011.553752.Kanmani P., Satish Kumar R., Yuvaraj N., Paari K.A., Pat-tukumar V., Arul V. Probiotics and its functionally valuable prod-ucts-a review. Crit Rev Food Sci Nutr. 2013; 53(6): 641-58. doi: 10.1080/10408398.2011.553752.Sorokulova I. Modern status and perspectives of Bacillus bacteria as probiotics. J. Prob. Health. 2013; 1(4). doi: 10.4172/2329-8901.1000e106.Sorokulova I. Modern status and perspectives of Bacillus bacteria as probiotics. J. Prob. Health. 2013; 1(4). doi: 10.4172/2329-8901.1000e106.Bernardeau M., Lehtinen M.J., Forssten S.D., Nurminen P. Importance of the gastrointestinal life cycle of Bacillus for probiotic functionality. J Food Sci Technol. 2017; 54(8): 2570-84. doi: 10.1007/s13197-017-2688-3.Bernardeau M., Lehtinen M.J., Forssten S.D., Nurminen P. Importance of the gastrointestinal life cycle of Bacillus for probiotic functionality. J Food Sci Technol. 2017; 54(8): 2570-84. doi: 10.1007/s13197-017-2688-3.Jeżewska-Frąckowiak J., Seroczyńska K., Banaszczyk J., Jedrzejczak G., Żylicz-Stachula A., Skowron P.M. The promises and risks of probiotic Bacillus species. Acta Biochim Pol. 2018; 65(4): 509-19. doi: 10.18388/abp.2018_2652.Jeżewska-Frąckowiak J., Seroczyńska K., Banaszczyk J., Jedrzejczak G., Żylicz-Stachula A., Skowron P.M. The promises and risks of probiotic Bacillus species. Acta Biochim Pol. 2018; 65(4): 509-19. doi: 10.18388/abp.2018_2652.Lee N.K., Won-Suck Kim W.S., Paik H.D. Bacillus strains as human probiotics: characterization, safety, microbiome, and probiotic carrier. Food Sci Biotechnol. 2019; 28(5): 1297-305. doi: 10.1007/s10068-019-00691-9.Lee N.K., Won-Suck Kim W.S., Paik H.D. Bacillus strains as human probiotics: characterization, safety, microbiome, and probiotic carrier. Food Sci Biotechnol. 2019; 28(5): 1297-305. doi: 10.1007/s10068-019-00691-9.RiazRajokaM.S., ZhaoH., Lu Y., LianZ., LiN., HussainN., ShaoD., Jin M., Li Q., Shi J. Anticancer potential against cervix cancer (HeLa) cell line of probiotic Lactobacillus casei and Lactobacillus paracasei strains isolated from human breast milk. Food Funct. 2018; 9(5): 2705-15. doi: 10.1039/c8fo00547h.RiazRajokaM.S., ZhaoH., Lu Y., LianZ., LiN., HussainN., ShaoD., Jin M., Li Q., Shi J. Anticancer potential against cervix cancer (HeLa) cell line of probiotic Lactobacillus casei and Lactobacillus paracasei strains isolated from human breast milk. Food Funct. 2018; 9(5): 2705-15. doi: 10.1039/c8fo00547h.Wang K.D., Xu D.J., Wang B.Y., Yan D.H., Lv Z., Su J.R. Inhibitory Effect of Vaginal Lactobacillus Supernatants on Cervical Cancer Cells. Probiotics Antimicrob Proteins. 2018; 10(2): 236-42. doi: 10.1007/s12602-017-9339-x.Wang K.D., Xu D.J., Wang B.Y., Yan D.H., Lv Z., Su J.R. Inhibitory Effect of Vaginal Lactobacillus Supernatants on Cervical Cancer Cells. Probiotics Antimicrob Proteins. 2018; 10(2): 236-42. doi: 10.1007/s12602-017-9339-x.Shin R., Itoh Y., Kataoka M., Iino-Miura S., Miura R., Mizutani T., Fujisawa T. Anti-tumor activity of heat-killed Lactobacillus plantarum BF-LP284 on Meth-A tumor cells in BALB/c mice. Int J Food Sci Nutr. 2016; 67(6): 641-49. doi: 10.1080/09637486.2016.1185771.Shin R., Itoh Y., Kataoka M., Iino-Miura S., Miura R., Mizutani T., Fujisawa T. Anti-tumor activity of heat-killed Lactobacillus plantarum BF-LP284 on Meth-A tumor cells in BALB/c mice. Int J Food Sci Nutr. 2016; 67(6): 641-49. doi: 10.1080/09637486.2016.1185771.Dubey V., Ghosh A.R., Bishayee K., Khuda-Bukhsh A.R. Appraisal of the anti-cancer potential of probiotic Pediococcus pentosaceus GS4 against colon cancer: in vitro and in vivo approaches. J. Funct. Foods. 2016; 23: 66-79. https://doi.org/10.1016/j.jff.2016.02.032.Dubey V., Ghosh A.R., Bishayee K., Khuda-Bukhsh A.R. Appraisal of the anti-cancer potential of probiotic Pediococcus pentosaceus GS4 against colon cancer: in vitro and in vivo approaches. J. Funct. Foods. 2016; 23: 66-79. https://doi.org/10.1016/j.jff.2016.02.032.Arai S., Iwabuchi N., Takahashi S., Xiao J.Z., Abe F., Hachimura S. Orally administered heat-killed Lactobacillus paracasei MCC1849 enhances antigen-specific IgA secretion and induces follicular helper T cells in mice. PLoS One. 2018; 13(6). doi: 10.1371/journal.pone.0199018.Arai S., Iwabuchi N., Takahashi S., Xiao J.Z., Abe F., Hachimura S. Orally administered heat-killed Lactobacillus paracasei MCC1849 enhances antigen-specific IgA secretion and induces follicular helper T cells in mice. PLoS One. 2018; 13(6). doi: 10.1371/journal.pone.0199018.Sungur T., Aslim B., Karaaslan C., Aktas B. Impact of Exopolysaccharides (EPSs) of Lactobacillus gasseri strains isolated from human vagina on cervical tumor cells (HeLa). Anaerobe. 2017; 47: 137-44. doi: 10.1016/j.anaerobe.2017.05.013.Sungur T., Aslim B., Karaaslan C., Aktas B. Impact of Exopolysaccharides (EPSs) of Lactobacillus gasseri strains isolated from human vagina on cervical tumor cells (HeLa). Anaerobe. 2017; 47: 137-44. doi: 10.1016/j.anaerobe.2017.05.013.Li X., Wang H., Du X., Yu W., Jiang J., Geng Y., Guo X., Fan X., Ma C. Lactobacilli inhibit cervical cancer cell migration in vitro and reduce tumor burden in vivo through upregulation of E-cadherin. Oncol Rep. 2017; 38(3): 1561-68. doi: 10.3892/or.2017.5791.Li X., Wang H., Du X., Yu W., Jiang J., Geng Y., Guo X., Fan X., Ma C. Lactobacilli inhibit cervical cancer cell migration in vitro and reduce tumor burden in vivo through upregulation of E-cadherin. Oncol Rep. 2017; 38(3): 1561-68. doi: 10.3892/or.2017.5791.Yin T.Q., Ou-Yang X., Jiao F.Y., Huang L.P., Tang X.D., Ren B.Q. Pseudomonas aeruginosa mannose-sensitive hemagglutinin inhibits proliferation and invasion via the PTEN/AKT pathway in HeLa cells. Oncotarget. 2016; 7(24): 37121-31. doi: 10.18632/oncotarget.9467.Yin T.Q., Ou-Yang X., Jiao F.Y., Huang L.P., Tang X.D., Ren B.Q. Pseudomonas aeruginosa mannose-sensitive hemagglutinin inhibits proliferation and invasion via the PTEN/AKT pathway in HeLa cells. Oncotarget. 2016; 7(24): 37121-31. doi: 10.18632/oncotarget.9467.Peng M., Tabashsum Z., Patel P., Bernhardt C., Biswas D. Linoleic Acids Overproducing Lactobacillus casei Limits Growth, Survival, and Virulence of Salmonella Typhimurium and Enterohaemorrhagic Escherichia coli. Front Microbiol. 2018; 9. doi: 10.3389/fmicb.2018.02663.Peng M., Tabashsum Z., Patel P., Bernhardt C., Biswas D. Linoleic Acids Overproducing Lactobacillus casei Limits Growth, Survival, and Virulence of Salmonella Typhimurium and Enterohaemorrhagic Escherichia coli. Front Microbiol. 2018; 9. doi: 10.3389/fmicb.2018.02663.Cha M.K., Lee D.K., An H.M., Lee S.W., Shin S.H., Kwon J.H., Kim K.J., Ha N.J. Antiviral activity of Bifidobacterium adolescentis SPM1005-A on human papillomavirus type 16. BMC Med. 2012; 10: 72. doi: 10.1186/1741-7015-10-72.Cha M.K., Lee D.K., An H.M., Lee S.W., Shin S.H., Kwon J.H., Kim K.J., Ha N.J. Antiviral activity of Bifidobacterium adolescentis SPM1005-A on human papillomavirus type 16. BMC Med. 2012; 10: 72. doi: 10.1186/1741-7015-10-72.ChuahLO.,FooHR.,Loh T.C., MohammedAUtheenN.B., YeapS.K., Abdul Mutalib N.E., Abdul Rahim R., Yusoff K. Postbiotic metabolites produced by Lactobacillus plantarum strains exert selective cytotoxicity effects on cancer cells. BMC Complement Altern Med. 2019; 19(1). doi: 10.1186/s12906-019-2528-2.ChuahLO.,FooHR.,Loh T.C., MohammedAUtheenN.B., YeapS.K., Abdul Mutalib N.E., Abdul Rahim R., Yusoff K. Postbiotic metabolites produced by Lactobacillus plantarum strains exert selective cytotoxicity effects on cancer cells. BMC Complement Altern Med. 2019; 19(1). doi: 10.1186/s12906-019-2528-2.Ciffo F. Determination of the spectrum of antibiotic resistance of the “Bacillus subtilis” strains of Enterogermina. Chemioterapia. 1984; 3(1): 45-52.Ciffo F. Determination of the spectrum of antibiotic resistance of the “Bacillus subtilis” strains of Enterogermina. Chemioterapia. 1984; 3(1): 45-52.MarsegliaG.L., ToscaM., CirilloI.,LicariA.,LeoneM.,MarsegliaA., Castellazzi A.M., Ciprandi G. Efficacy of Bacillus clausii spores in the prevention of recurrent respiratory infections in children: a pilot study. Ther Clin Risk Manag. 2007; 3(1): 13-17. doi: 10.2147/tcrm.2007.3.1.13.MarsegliaG.L., ToscaM., CirilloI.,LicariA.,LeoneM.,MarsegliaA., Castellazzi A.M., Ciprandi G. Efficacy of Bacillus clausii spores in the prevention of recurrent respiratory infections in children: a pilot study. Ther Clin Risk Manag. 2007; 3(1): 13-17. doi: 10.2147/tcrm.2007.3.1.13.Hyronimus B., Le Marrec C., Urdaci M.C. Coagulin, a bacteriocin-like inhibitory substance produced by Bacillus coagulans I4. J Appl Microbiol. 1998; 85(1): 42-50. doi: 10.1046/j.1365-2672.1998.00466.x.Hyronimus B., Le Marrec C., Urdaci M.C. Coagulin, a bacteriocin-like inhibitory substance produced by Bacillus coagulans I4. J Appl Microbiol. 1998; 85(1): 42-50. doi: 10.1046/j.1365-2672.1998.00466.x.Mandel D.R., Eichas K., Holmes J. Bacillus coagulans: a viable adjunct therapy for relieving symptoms of rheumatoid arthritis according to a randomized, controlled trial. BMC Complement Altern Med. 2010; 10: 1. doi: 10.1186/1472-6882-10-1.Mandel D.R., Eichas K., Holmes J. Bacillus coagulans: a viable adjunct therapy for relieving symptoms of rheumatoid arthritis according to a randomized, controlled trial. BMC Complement Altern Med. 2010; 10: 1. doi: 10.1186/1472-6882-10-1.Le Marrec C., Hyronimus B., Bressollier P., Verneuil B., Urdaci M.C. Biochemical and genetic characterization of coagulin, a new antilisterial bacteriocin in the pediocin family of bacteriocins, produced by Bacillus coagulans I(4). Appl Environ Microbiol. 2000; 66(12): 5213-20. doi: 10.1128/AEM.66.12.5213-5220.2000.Le Marrec C., Hyronimus B., Bressollier P., Verneuil B., Urdaci M.C. Biochemical and genetic characterization of coagulin, a new antilisterial bacteriocin in the pediocin family of bacteriocins, produced by Bacillus coagulans I(4). Appl Environ Microbiol. 2000; 66(12): 5213-20. doi: 10.1128/AEM.66.12.5213-5220.2000.Hong H.A., Duc le H., Cutting S.M. The use of bacterial spore formers as probiotics. FEMS Microbiol Rev. 2005; 29(4): 813-35. doi: 10.1016/j.femsre.2004.12.001.Hong H.A., Duc le H., Cutting S.M. The use of bacterial spore formers as probiotics. FEMS Microbiol Rev. 2005; 29(4): 813-35. doi: 10.1016/j.femsre.2004.12.001.Yang HJ., Kwon D.Y., Kim HJ., Kim MJ., Jung D.Y., Kang HJ., Kim D.S., Kang S., Moon N.R., Shin B.K., Park S. Fermenting soybeans with Bacillus licheniformis potentiates their capacity to improve cognitive function and glucose homeostaisis in diabetic rats with experimental Alzheimer's type dementia. Eur J Nutr. 2015; 54(1): 77-88. doi: 10.1007/s00394-014-0687-y.Yang HJ., Kwon D.Y., Kim HJ., Kim MJ., Jung D.Y., Kang HJ., Kim D.S., Kang S., Moon N.R., Shin B.K., Park S. Fermenting soybeans with Bacillus licheniformis potentiates their capacity to improve cognitive function and glucose homeostaisis in diabetic rats with experimental Alzheimer's type dementia. Eur J Nutr. 2015; 54(1): 77-88. doi: 10.1007/s00394-014-0687-y.Pan X., Cai Y., Kong L., Xiao C., Zhu Q., Song Z. Probiotic Effects of Bacillus licheniformis DSM5749 on Growth Performance and Intestinal Microecological Balance of Laying Hens. Front Nutr. 2022; 9. doi: 10.3389/fnut.2022.868093.Pan X., Cai Y., Kong L., Xiao C., Zhu Q., Song Z. Probiotic Effects of Bacillus licheniformis DSM5749 on Growth Performance and Intestinal Microecological Balance of Laying Hens. Front Nutr. 2022; 9. doi: 10.3389/fnut.2022.868093.Paik H.D., Park J.S., Park E. Effects of Bacillus polyfermenticus SCD on lipid and antioxidant metabolisms in rats fed a high-fat and high-cholesterol diet. Biol Pharm Bull. 2005; 28(7): 1270-74. doi: 10.1248/bpb.28.1270.Paik H.D., Park J.S., Park E. Effects of Bacillus polyfermenticus SCD on lipid and antioxidant metabolisms in rats fed a high-fat and high-cholesterol diet. Biol Pharm Bull. 2005; 28(7): 1270-74. doi: 10.1248/bpb.28.1270.Ma E.L., Choi Y.J., Choi J., Pothoulakis C., Rhee S.H., Im E. The anticancer effect of probiotic Bacillus polyfermenticus on human colon cancer cells is mediated through ErbB2 and ErbB3 inhibition. Int J Cancer. 2010; 127(4): 780-90. doi: 10.1002/ijc.25011. Erratum in: Int J Cancer. 2010; 127(11).Ma E.L., Choi Y.J., Choi J., Pothoulakis C., Rhee S.H., Im E. The anticancer effect of probiotic Bacillus polyfermenticus on human colon cancer cells is mediated through ErbB2 and ErbB3 inhibition. Int J Cancer. 2010; 127(4): 780-90. doi: 10.1002/ijc.25011. Erratum in: Int J Cancer. 2010; 127(11).Lee N.K., Son S.H., Jeon E.B., Jung G.H., Lee J.Y., Paik H.D. The prophylactic effect of probiotic Bacillus polyfermenticus KU3 against cancer cells. J. Funct. Foods. 2015; 14: 513-18. doi: 10.1016/j.jff.2015.02.019.Lee N.K., Son S.H., Jeon E.B., Jung G.H., Lee J.Y., Paik H.D. The prophylactic effect of probiotic Bacillus polyfermenticus KU3 against cancer cells. J. Funct. Foods. 2015; 14: 513-18. doi: 10.1016/j.jff.2015.02.019.Ma Y., Wang W., Zhang H., Wang J., Zhang W., Gao J., Wu S., Qi G. Supplemental Bacillus subtilis DSM 32315 manipulates intestinal structure and microbial composition in broiler chickens. Sci Rep. 2018; 8(1). doi: 10.1038/s41598-018-33762-8.Ma Y., Wang W., Zhang H., Wang J., Zhang W., Gao J., Wu S., Qi G. Supplemental Bacillus subtilis DSM 32315 manipulates intestinal structure and microbial composition in broiler chickens. Sci Rep. 2018; 8(1). doi: 10.1038/s41598-018-33762-8.Hoa N.T., Baccigalupi L., Huxham A., Smertenko A., Van P.H., Ammendola S., Ricca E., Cutting A.S. Characterization of Bacillus species used for oral bacteriotherapy and bacterioprophylaxis of gastrointestinal disorders. Appl Environ Microbiol. 2000; 66(12): 5241-47. doi: 10.1128/AEM.66.12.5241-5247.2000.Hoa N.T., Baccigalupi L., Huxham A., Smertenko A., Van P.H., Ammendola S., Ricca E., Cutting A.S. Characterization of Bacillus species used for oral bacteriotherapy and bacterioprophylaxis of gastrointestinal disorders. Appl Environ Microbiol. 2000; 66(12): 5241-47. doi: 10.1128/AEM.66.12.5241-5247.2000.Jeon H.L., Lee N.K., Yang S.J., Kim W.S., Paik H.D. Probiotic characterization of Bacillus subtilis P223 isolated from kimchi. Food Sci Biotechnol. 2017; 26(6): 1641-48. doi: 10.1007/s10068-017-0148-5.Jeon H.L., Lee N.K., Yang S.J., Kim W.S., Paik H.D. Probiotic characterization of Bacillus subtilis P223 isolated from kimchi. Food Sci Biotechnol. 2017; 26(6): 1641-48. doi: 10.1007/s10068-017-0148-5.Pinchuk I.V., Bressollier P., Verneuil B., Fenet B., Sorokulova I.B., Megraud F., Urdaci M.C. In vitro anti-Helicobacter pylori activity of the probiotic strain Bacillus subtilis 3 is due to secretion of antibiotics. Antimicrob Agents Chemother. 2001; 45(11): 3156-61. doi: 10.1128/AAC.45.11.3156-3161.2001.Pinchuk I.V., Bressollier P., Verneuil B., Fenet B., Sorokulova I.B., Megraud F., Urdaci M.C. In vitro anti-Helicobacter pylori activity of the probiotic strain Bacillus subtilis 3 is due to secretion of antibiotics. Antimicrob Agents Chemother. 2001; 45(11): 3156-61. doi: 10.1128/AAC.45.11.3156-3161.2001.Chudnovskaya N.V., Ribalko S.L., Sorokulova I.B., Smirnov V.V., Belyavskaya V.A. Antiviral activity of Bacillus probiotics. Dopovidi Nac Acad Nauk Ukraini. 1995; 124-26.Chudnovskaya N.V., Ribalko S.L., Sorokulova I.B., Smirnov V.V., Belyavskaya V.A. Antiviral activity of Bacillus probiotics. Dopovidi Nac Acad Nauk Ukraini. 1995; 124-26.Starosila D., Rybalko S., Varbanetz L., Ivanskaya N., Sorokulova I. Anti-influenza Activity of a Bacillus subtilis Probiotic Strain. Antimicrob Agents Chemother. 2017; 61(7). doi: 10.1128/AAC.00539-17.Starosila D., Rybalko S., Varbanetz L., Ivanskaya N., Sorokulova I. Anti-influenza Activity of a Bacillus subtilis Probiotic Strain. Antimicrob Agents Chemother. 2017; 61(7). doi: 10.1128/AAC.00539-17.Elshaghabee F.M.F., Rokana N., Gulhane R.D., Sharma C., Panwar H. Bacillus As Potential Probiotics: Status, Concerns, and Future Perspectives. Front Microbiol. 2017; 8. doi: 10.3389/fmicb.2017.01490.Elshaghabee F.M.F., Rokana N., Gulhane R.D., Sharma C., Panwar H. Bacillus As Potential Probiotics: Status, Concerns, and Future Perspectives. Front Microbiol. 2017; 8. doi: 10.3389/fmicb.2017.01490.Sanders M.E., Morelli L., Tompkins T.A. Sporeformers as Human Probiotics: Bacillus, Sporolactobacillus, and Brevibacillus. Compr Rev Food Sci Food Saf. 2003; 2(3): 101-10. doi: 10.1111/j.1541-4337.2003.tb00017.x.Sanders M.E., Morelli L., Tompkins T.A. Sporeformers as Human Probiotics: Bacillus, Sporolactobacillus, and Brevibacillus. Compr Rev Food Sci Food Saf. 2003; 2(3): 101-10. doi: 10.1111/j.1541-4337.2003.tb00017.x.Jacquier V., Nelson A., Jlali M., Rhayat L., Brinch K.S., Devillard E. Bacillus subtilis 29784 induces a shift in broiler gut microbiome toward butyrate-producing bacteria and improves intestinal histomor-phology and animal performance. Poult Sci. 2019; 98(6): 2548-54. doi: 10.3382/ps/pey602.Jacquier V., Nelson A., Jlali M., Rhayat L., Brinch K.S., Devillard E. Bacillus subtilis 29784 induces a shift in broiler gut microbiome toward butyrate-producing bacteria and improves intestinal histomor-phology and animal performance. Poult Sci. 2019; 98(6): 2548-54. doi: 10.3382/ps/pey602.Muscettola M., Grasso G., Blach-Olszewska Z., Migliaccio P., Borghesi-Nicoletti C., Giarratana M., Gallo V.C. Effects of Bacillus subtilis spores on interferon production. Pharmacol Res. 1992; 26s2: 176-77. doi: 10.1016/1043-6618(92)90652-r.Muscettola M., Grasso G., Blach-Olszewska Z., Migliaccio P., Borghesi-Nicoletti C., Giarratana M., Gallo V.C. Effects of Bacillus subtilis spores on interferon production. Pharmacol Res. 1992; 26s2: 176-77. doi: 10.1016/1043-6618(92)90652-r.Bortoluzzi C., Serpa Vieira B., de Paula Dorigam J.C., Menconi A., Sokale A., Doranalli K., Applegate T.J. Bacillus subtilis DSM 32315 Supplementation Attenuates the Effects of Clostridium perfringens Challenge on the Growth Performance and Intestinal Microbiota of Broiler Chickens. Microorganisms. 2019; 7(3). doi: 10.3390/microorganisms7030071.Bortoluzzi C., Serpa Vieira B., de Paula Dorigam J.C., Menconi A., Sokale A., Doranalli K., Applegate T.J. Bacillus subtilis DSM 32315 Supplementation Attenuates the Effects of Clostridium perfringens Challenge on the Growth Performance and Intestinal Microbiota of Broiler Chickens. Microorganisms. 2019; 7(3). doi: 10.3390/microorganisms7030071.Grasso G., Migliaccio P., Tanganelli C., Brugo M.A., Muscettola M. Restorative effect of Bacillus subtilis spores on interferon production in aged mice. Ann NY Acad Sci. 1994; 717: 198-208. doi: 10.1111/j.1749-6632.1994.tb12088.x.Grasso G., Migliaccio P., Tanganelli C., Brugo M.A., Muscettola M. Restorative effect of Bacillus subtilis spores on interferon production in aged mice. Ann NY Acad Sci. 1994; 717: 198-208. doi: 10.1111/j.1749-6632.1994.tb12088.x.

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