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Модуляция микробиоты кишечника как потенциал для повышения эффективности и снижения токсичности химиотерапии детей с острыми лейкозами
Модуляция микробиоты кишечника как потенциал для повышения эффективности и снижения токсичности химиотерапии детей с острыми лейкозами
Муртазин А.А., Исламгулов А.Х., Малиевский В.А. Модуляция микробиоты кишечника как потенциал для повышения эффективности и снижения токсичности химиотерапии детей с острыми лейкозами. Consilium Medicum. 2026;27(5):1–8. DOI: 10.26442/20751753.2026.5.203517
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Аннотация
Обоснование. Острые лейкозы (ОЛ) – наиболее распространенная онкологическая патология в детской популяции. Несмотря на достигнутый прогресс в лечении, связанный с химиотерапией (ХТ) и методом трансплантации гемопоэтических стволовых клеток, лечение этого заболевания сопровождается различными осложнениями, такими как мукозиты, фебрильная нейтропения, системные инфекции и реакция «трансплантат против хозяина» (РТПХ). Кишечная микробиота (КМ) играет важную роль в модуляции эффективности ХТ и развитии ее токсичности. Индуцированный на фоне ХТ дисбиоз ассоциирован с ухудшением исходов лечения, что делает актуальным поиск стратегий его коррекции.
Цель. Систематизировать современные данные о роли КМ в патогенезе осложнений и эффективности терапии ОЛ у детей, а также проанализировать перспективные стратегии ее целенаправленной модуляции, нацеленные на улучшение результатов лечения.
Материалы и методы. Проведен систематический обзор литературы в соответствии с рекомендациями PRISMA. Поиск публикаций осуществлялся в базах данных PubMed/MEDLINE, Google Scholar и eLIBRARY за период с 2014 по 2025 г. Из 5628 найденых публикаций после исключения дубликатов и применения критериев включения/исключения в анализ включено 63 релевантных источника.
Результаты. Продемонстрировано, что ХТ-индуцированный дисбиоз приводит к снижению α-разнообразия, характеризующегося уменьшением численности комменсальных родов (Faecalibacterium, Lachnospiraceae) и доминированием условно-патогенных бактерий (Enterobacteriaceae). Эти изменения ведут к развитию тяжелого мукозита, фебрильной нейтропении, системных инфекций и РТПХ. КМ также влияет на метаболизм цитостатиков (например, инактивация гемцитабина), целостность кишечного барьера (через продукцию короткоцепочечных жирных кислот) и системный иммунный ответ. Среди перспективных методов коррекции дисбиоза выделяются такие, как трансплантация фекальной микробиоты, демонстрирующая эффективность при стероидорезистентной РТПХ, применение пробиотиков, пребиотиков, а также персонализированные диеты с высоким содержанием клетчатки, синтетические микробные консорциумы и живые биологические средства.
Заключение. Интеграция стратегий модуляции КМ в стандартные протоколы лечения ОЛ у детей представляет собой перспективное направление, позволяющее повысить эффективность ХТ. Однако для валидации и стандартизации этой стратегии необходимы дальнейшие рандомизированные контролируемые исследования, направленные на оценку их долгосрочной безопасности и эффективности.
Ключевые слова: онкология, лейкозы, химиотерапия у детей, токсичность химотерапии, микробиота кишечника, дисбиоз, короткоцепочечные жирные кислоты, пробиотики, трансплантация фекальной микробиоты, персонализированная медицина
Aim. To systematize current data on the role of GM in the pathogenesis of complications and the efficacy of AL therapy in children, and to analyze promising strategies for its targeted modulation aimed at improving treatment outcomes.
Materials and methods. A systematic literature review was conducted in accordance with the PRISMA guidelines. The search for publications was performed in the PubMed/MEDLINE, Google Scholar, and eLIBRARY databases for the period from 2014 to 2025. Out of 5628 identified publications, after excluding duplicates and applying inclusion/exclusion criteria, 63 relevant sources were included in the analysis.
Results. It was demonstrated that CT-induced dysbiosis leads to reduced alpha-diversity, characterized by a decreased abundance of commensal genera (e.g., Faecalibacterium, Lachnospiraceae) and dominance of opportunistic pathogens (e.g., Enterobacteriaceae). These alterations contribute to the development of severe mucositis, febrile neutropenia, systemic infections, and GVHD. The GM also influences the metabolism of cytostatic drugs (e.g., gemcitabine inactivation), intestinal barrier integrity (via the production of short-chain fatty acids), and the systemic immune response. Promising methods for dysbiosis correction include fecal microbiota transplantation, which has shown efficacy in steroid-refractory acute GVHD, as well as the use of probiotics, prebiotics, personalized high-fiber diets, synthetic microbial consortia, and live biotherapeutic products.
Conclusion. The integration of GM modulation strategies into standard AL treatment protocols for children represents a promising approach to enhance the efficacy of CT. However, further randomized controlled trials are required to validate and standardize these strategies, focusing on the assessment of their long-term safety and efficacy.
Keywords: oncology, leukemias, pediatric chemotherapy, chemotherapy toxicity, gut microbiota, dysbiosis, short-chain fatty acids, probiotics, fecal microbiota transplantation, personalized medicine
Цель. Систематизировать современные данные о роли КМ в патогенезе осложнений и эффективности терапии ОЛ у детей, а также проанализировать перспективные стратегии ее целенаправленной модуляции, нацеленные на улучшение результатов лечения.
Материалы и методы. Проведен систематический обзор литературы в соответствии с рекомендациями PRISMA. Поиск публикаций осуществлялся в базах данных PubMed/MEDLINE, Google Scholar и eLIBRARY за период с 2014 по 2025 г. Из 5628 найденых публикаций после исключения дубликатов и применения критериев включения/исключения в анализ включено 63 релевантных источника.
Результаты. Продемонстрировано, что ХТ-индуцированный дисбиоз приводит к снижению α-разнообразия, характеризующегося уменьшением численности комменсальных родов (Faecalibacterium, Lachnospiraceae) и доминированием условно-патогенных бактерий (Enterobacteriaceae). Эти изменения ведут к развитию тяжелого мукозита, фебрильной нейтропении, системных инфекций и РТПХ. КМ также влияет на метаболизм цитостатиков (например, инактивация гемцитабина), целостность кишечного барьера (через продукцию короткоцепочечных жирных кислот) и системный иммунный ответ. Среди перспективных методов коррекции дисбиоза выделяются такие, как трансплантация фекальной микробиоты, демонстрирующая эффективность при стероидорезистентной РТПХ, применение пробиотиков, пребиотиков, а также персонализированные диеты с высоким содержанием клетчатки, синтетические микробные консорциумы и живые биологические средства.
Заключение. Интеграция стратегий модуляции КМ в стандартные протоколы лечения ОЛ у детей представляет собой перспективное направление, позволяющее повысить эффективность ХТ. Однако для валидации и стандартизации этой стратегии необходимы дальнейшие рандомизированные контролируемые исследования, направленные на оценку их долгосрочной безопасности и эффективности.
Ключевые слова: онкология, лейкозы, химиотерапия у детей, токсичность химотерапии, микробиота кишечника, дисбиоз, короткоцепочечные жирные кислоты, пробиотики, трансплантация фекальной микробиоты, персонализированная медицина
________________________________________________
Aim. To systematize current data on the role of GM in the pathogenesis of complications and the efficacy of AL therapy in children, and to analyze promising strategies for its targeted modulation aimed at improving treatment outcomes.
Materials and methods. A systematic literature review was conducted in accordance with the PRISMA guidelines. The search for publications was performed in the PubMed/MEDLINE, Google Scholar, and eLIBRARY databases for the period from 2014 to 2025. Out of 5628 identified publications, after excluding duplicates and applying inclusion/exclusion criteria, 63 relevant sources were included in the analysis.
Results. It was demonstrated that CT-induced dysbiosis leads to reduced alpha-diversity, characterized by a decreased abundance of commensal genera (e.g., Faecalibacterium, Lachnospiraceae) and dominance of opportunistic pathogens (e.g., Enterobacteriaceae). These alterations contribute to the development of severe mucositis, febrile neutropenia, systemic infections, and GVHD. The GM also influences the metabolism of cytostatic drugs (e.g., gemcitabine inactivation), intestinal barrier integrity (via the production of short-chain fatty acids), and the systemic immune response. Promising methods for dysbiosis correction include fecal microbiota transplantation, which has shown efficacy in steroid-refractory acute GVHD, as well as the use of probiotics, prebiotics, personalized high-fiber diets, synthetic microbial consortia, and live biotherapeutic products.
Conclusion. The integration of GM modulation strategies into standard AL treatment protocols for children represents a promising approach to enhance the efficacy of CT. However, further randomized controlled trials are required to validate and standardize these strategies, focusing on the assessment of their long-term safety and efficacy.
Keywords: oncology, leukemias, pediatric chemotherapy, chemotherapy toxicity, gut microbiota, dysbiosis, short-chain fatty acids, probiotics, fecal microbiota transplantation, personalized medicine
Полный текст
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54. Lagoumintzis G, Patrinos GP. Triangulating nutrigenomics, metabolomics and microbiomics toward personalized nutrition and healthy living. Human Genomics. 2023;17(1):109. DOI:10.1186/s40246-023-00561-w
55. Schemczssen-Graeff Z, Pileggi M. Probiotics and live biotherapeutic products aiming at cancer mitigation and patient recover. Front Genet. 2022;13:921972. DOI:10.3389/fgene.2022.921972
56. Che S, Men Y. Synthetic microbial consortia for biosynthesis and biodegradation: promises and challenges. J Ind Microbiol Biotechnol. 2019;46(9-10):1343-58. DOI:10.1007/s10295-019-02211-4
57. Van der Lelie D, Oka A, Taghavi S, et al. Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis. Nat Commun. 2021;12(1):3105. DOI:10.1038/s41467-021-23460-x
58. Kylilis N, Tuza ZA, Stan GB, Polizzi KM. Tools for engineering coordinated system behaviour in synthetic microbial consortia. Nat Commun. 2018;9(1):2677. DOI:10.1038/s41467-018-05046-2
59. Cordaillat-Simmons M, Rouanet A, Pot B. Live biotherapeutic products: the importance of a defined regulatory framework. Exp Mol Med. 2020;52(9):1397-406. DOI:10.1038/s12276-020-0437-6
60. Rouanet A, Bolca S, Bru A, et al. Live biotherapeutic products, a road map for safety assessment. Front Med (Lausanne). 2020;7:237. DOI:10.3389/fmed.2020.00237
61. Lim ECN, Lim CED. Microbiome-Targeted Therapies in Gastrointestinal Diseases: Clinical Evidence and Emerging Innovations. Acta Microbiologica Hellenica. 2025;70(3):36. DOI:10.3390/amh70030036
62. Nowicka A, Tomczak H, Szałek E, et al. Microbial Crosstalk with Therapy: Pharmacomicrobiomics in AML-One Step Closer to Personalized Medicine. Biomedicines. 2025;13(7):1761. DOI:10.3390/biomedicines13071761
2. Masetti R, Muratore E, Leardini D, et al. Gut microbiome in pediatric acute leukemia: from predisposition to cure. Blood Adv. 2021;5(22):4619-29. DOI:10.1182/bloodadvances.2021005129
3. Antoshin MM, Rumyantsev SA, Belmer SV. Intestinal microbiota: general concepts and significance in acute lymphoblastic leukemia in children (literature review). Trudnyi Patsient. 2018;16(8-9):49-53. DOI:10.24411/2074-1995-2018-10009
4. Oldenburg M, Rüchel N, Janssen S, et al. The Microbiome in Childhood Acute Lymphoblastic Leukemia. Cancers (Basel). 2021;13(19):4947. DOI:10.3390/cancers13194947
5. Peppas I, Ford AM, Furness CL, Greaves MF. Gut microbiome immaturity and childhood acute lymphoblastic leukaemia. Nat Rev Cancer. 2023;23(8):565-76. DOI:10.1038/s41568-023-00584-4
6. Nycz BT, Dominguez SR, Friedman D, et al. Evaluation of bloodstream infections, Clostridium difficile infections, and gut microbiota in pediatric oncology patients. PLoS One. 2018;13(1):e0191232. DOI:10.1371/journal.pone.0191232
7. Goloshchapov OV, Churakina DV, Kucher MA, et al. Fecal microbiota transplantation in critical condition of patients in oncohematological practice. Bulletin of Anesthesiology and Resuscitation. 2019;16(3):63-73 (in Russian). DOI:10.21292/2078-5658-2019-16-3-63-73
8. Chrysostomou D, Roberts LA, Marchesi JR, Kinross JM. Gut microbiota modulation of efficacy and toxicity of cancer chemotherapy and immunotherapy. Gastroenterology. 2023;164(2):198-213. DOI:10.1053/j.gastro.2022.10.018
9. Olekhnovich EI, Manolov AI, Pavlenko AV, et al. Influence of gut microbiome on the efficacy of antitumor immunotherapy. Biomed Khim. 2020;66(1):54-63 (in Russian). DOI:10.18097/PBMC20206601054
10. Bellone M, Brevi A, Huber S. Microbiota-propelled T helper 17 cells in inflammatory diseases and cancer. Microbiol Mol Biol Rev. 2020;84(2):e00064-19. DOI:10.1128/mmbr.00064-19
11. Mahdy MS, Azmy AF, Dishisha T, et al. Irinotecan-gut microbiota interactions and the capability of probiotics to mitigate Irinotecan-associated toxicity. BMC Microbiol. 2023;23(1):53. DOI:10.1186/s12866-023-02791-3
12. Zeng Y, Shi Q, Liu X, et al. Dynamic gut microbiota changes in patients with advanced malignancies experiencing secondary resistance to immune checkpoint inhibitors and immune-related adverse events. Front Oncol. 2023;13:1144534. DOI:10.3389/fonc.2023.1144534
13. Ni Y, Lohinai Z, Heshiki Y, et al. Distinct composition and metabolic functions of human gut microbiota are associated with cachexia in lung cancer patients. The ISME Journal. 2021;15(11):3207-20. DOI:10.1038/s41396-021-00998-8
14. Nguyen SM, Tran HT, Long J, et al. Gut microbiome in association with chemotherapy-induced toxicities among patients with breast cancer. Cancer. 2024;130(11):2014-30. DOI:10.1002/cncr.35229
15. Giromini C, Baldi A, Rebucci R, et al. Role of Short Chain Fatty Acids to Counteract Inflammatory Stress and Mucus Production in Human Intestinal HT29-MTX-E12 Cells. Foods. 2022;11(13):1983. DOI:10.3390/foods11131983
16. Cazzaniga M, Cardinali M, Di Pierro F, et al. The Potential Role of Probiotics, Especially Butyrate Producers, in the Management of Gastrointestinal Mucositis Induced by Oncologic Chemo-Radiotherapy. Int J Mol Sci. 2024;25(4):2306. DOI:10.3390/ijms25042306
17. Mendes I, Vale N. Overcoming Microbiome-Acquired Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma. Biomedicines. 2024;12(1):227. DOI:10.3390/biomedicines12010227
18. Yin B, Wang X, Yuan F, et al. Research progress on the effect of gut and tumor microbiota on antitumor efficacy and adverse effects of chemotherapy drugs. Front Microbiol. 2022;13:899111. DOI:10.3389/fmicb.2022.899111
19. Adel M, Khedr RA, Sayed AA, et al. Changes in Gut Microbial Diversity and Correlation with Clinical Outcome in Children with Acute Myeloid Leukemia Receiving Induction Chemotherapy. Children (Basel). 2025;12(9):1176. DOI:10.3390/children12091176
20. D’Amico F, Biagi E, Rampelli S, et al. Enteral Nutrition in Pediatric Patients Undergoing Hematopoietic SCT Promotes the Recovery of Gut Microbiome Homeostasis. Nutrients. 2019;11(12):2958. DOI:10.3390/nu11122958
21. Vazquez X, Lumbreras-Iglesias P, Rodicio MR, et al. Study of the intestinal microbiota composition and the effect of treatment with intensive chemotherapy in patients recovered from acute leukemia. Sci Rep. 2024;14(1):5585. DOI:10.1038/s41598-024-56054-w
22. Salvestrini V, Conti G, D'Amico F, et al. Gut Microbiome as a potential marker of hematologic recovery following induction therapy in acute myeloid leukemia patients. Cancer Med. 2025;14(3):e70501. DOI:10.1002/cam4.70501
23. Immonen E, Paulamäki L, Piippo H, et al. Oral microbiome diversity and composition before and after chemotherapy treatment in pediatric oncology patients. BMC Oral Health. 2025;25(1):981. DOI:10.1186/s12903-025-06405-4
24. Guarana M, Nucci M, Nouer SA. Shock and early death in hematologic patients with febrile neutropenia. Antimicrob Agents Chemother. 2019;63(11):e01250-19. DOI:10.1128/aac.01250-19
25. Song A, Shen N, Gan C, et al. Exploration of the relationship between intestinal flora changes and gut acute graft-versus-host disease after hematopoietic stem cell transplantation. Transl Pediatr. 2021;10(2):283-95. DOI:10.21037/tp-20-208
26. Chua LL, Rajasuriar R, Lim YA, et al. Temporal changes in gut microbiota profile in children with acute lymphoblastic leukemia prior to commencement-, during-, and post-cessation of chemotherapy. BMC Cancer. 2020;20(1):151. DOI:10.1186/s12885-020-6654-5
27. Margolis EB, Alfaro GM, Sun Y, et al. Microbiota predict infections and acute graft-versus-host disease after pediatric allogeneic hematopoietic stem cell transplantation. J Infect Dis. 2023;228(5):627-36. DOI:10.1093/infdis/jiad190
28. Biagi E, Zama D, Rampelli S, et al. Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders. BMC Med Genomics. 2019;12(1):49. DOI:10.1186/s12920-019-0494-7
29. Sayin S, Rosener B, Li CG, et al. Evolved bacterial resistance to the chemotherapy gemcitabine modulates its efficacy in co-cultured cancer cells. eLife. 2023;12:e83140. DOI:10.7554/eLife.83140
30. Xu G, Jiang Y, Sun C, et al. Role of Oral Bacteria in Mediating Gemcitabine Resistance in Pancreatic Cancer. Biomolecules. 2025;15(7):1018. DOI:10.3390/biom15071018
31. Meade S, Kiow J, Massaro C, et al. Gut microbiome-associated predictors as biomarkers of response to advanced therapies in inflammatory bowel disease: a systematic review. Gut Microbes. 2023;15(2):2287073. DOI:10.1080/19490976.2023.2287073
32. He Y, Fu L, Li Y, et al. Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8+ T cell immunity. Cell Metabolism. 2021;33(5):988-1000. DOI:10.1016/j.cmet.2021.03.002
33. Pavlova SI. The role of microbiota and flavonoids in maintaining the balance of helper and regulatory T-lymphocytes associated with the intestinal immune barrier. Voprosy Pitaniia. 2024;93(1):22-32 (in Russian). DOI:10.33029/0042-8833-2024-93-1-22-32
34. Anderson R, Theron AJ, Rapoport BL. Immunopathogenesis of immune checkpoint inhibitor-related adverse events: roles of the intestinal microbiome and Th17 cells. Front Immunol. 2019;10:2254. DOI:10.3389/fimmu.2019.02254
35. Pötgens SA, Lecop S, Havelange V, et al. Gut microbiota alterations induced by intensive chemotherapy in acute myeloid leukaemia patients are associated with gut barrier dysfunction and body weight loss. Clin Nutr. 2023;42(11):2214-28. DOI:10.1016/j.clnu.2023.09.021
36. Vicente-Dueñas C, Janssen S, Oldenburg M, et al. An intact gut microbiome protects genetically predisposed mice against leukemia. Blood. 2020;136(18):2003-17. DOI:10.1182/blood.2019004381
37. Yang B, Li W, Shi J. Preventive effect of probiotics on oral mucositis induced by anticancer therapy: a systematic review and meta-analysis of randomized controlled trials. BMC Oral Health. 2024;24(1):1159. DOI:10.1186/s12903-024-04955-7
38. Pedretti L, Leardini D, Muratore E, et al. Managing the Risk of Foodborne Infections in Pediatric Patients with Cancer: Is the Neutropenic Diet Still an Option? Nutrients. 2024;16(7):966. DOI:10.3390/nu16070966
39. Simiakova M, Bielik V. The pros and cons of probiotic use in pediatric oncology patients following treatment for acute lymphoblastic leukemia. Front Pediatr. 2024;12:1427185. DOI:10.3389/fped.2024.1427185
40. Diorio C, Robinson PD, Ammann RA, et al. Guideline for the management of clostridium difficile infection in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation recipients. J Clin Oncol. 2018;36(31):3162-71. DOI:10.1200/JCO.18.00407
41. Zhou S, Martin M, Powell C, et al. How to maintain a healthy gut microbiome in children with cancer? Gut microbiome association with diet in children with solid tumors postchemotherapy. OMICS. 2022;26(4):236-45. DOI:10.1089/omi.2022.0002
42. Gallotti B, Galvao I, Leles G, et al. Effects of dietary fibre intake in chemotherapy-induced mucositis in murine model. Br J Nutr. 2021;126(6):853-64. DOI:10.1017/S0007114520004924
43. Jamal R, Messaoudene M, de Figuieredo M, Routy B. Future indications and clinical management for fecal microbiota transplantation (FMT) in immuno-oncology. Semin Immunol. 2023;67:101754. DOI:10.1016/j.smim.2023.101754
44. Chen D, Wu J, Jin D, et al. Fecal microbiota transplantation in cancer management: Current status and perspectives. Int J Cancer. 2019;145(8):2021-31. DOI:10.1002/ijc.32003
45. Guo Z, He M, Shao L, et al. The role of fecal microbiota transplantation in the treatment of acute graft-versus-host disease. J Cancer Res Ther. 2024;20(7):1964-73. DOI:10.4103/jcrt.jcrt_33_24
46. Henig I, Yehudai-Ofir D, Zuckerman T. The clinical role of the gut microbiome and fecal microbiota transplantation in allogeneic stem cell transplantation. Haematologica. 2021;106(4):933-46. DOI:10.3324/haematol.2020.247395
47. Goloshchapov OV, Kucher MA, Moiseev IS, et al. Fecal microbiota transplantation in patients after allogeneic hematopoietic stem cell transplantation. Cell Therapy and Transplantation. 2018;7(3):56-7 (in Russian). DOI:10.21292/2078-5658-2019-16-3-63-73
48. Prayag PS. Patwardhan SA, Ajapuje PS, et al. Fecal Microbiota Transplantation for Clostridium difficile-associated Diarrhea in Hematopoietic Stem Cell Transplant Recipients: A Single-center Experience from a Tertiary Center in India. Indian J Crit Care Med. 2024;28(2):106-10. DOI:10.5005/jp-journals-10071-24607
49. Bou Zerdan M, Niforatos S, Nasr S, et al. Fecal Microbiota Transplant for Hematologic and Oncologic Diseases: Principle and Practice. Cancers (Basel). 2022;14(3):691. DOI:10.3390/cancers14030691
50. Zhou S, Martin M, Powell C, et al. Associations between Dietary Intakes and the Gut Microbiome in Children with Solid Tumors after Chemotherapy and Healthy Controls. Authorea Preprints. 2021;(2). DOI:10.22541/au.162526069.90949263/v1
51. Munteanu C, Schwartz B. Interactions between Dietary Antioxidants, Dietary Fiber and the Gut Microbiome: Their Putative Role in Inflammation and Cancer. Int J Mol Sci. 2024;25(15):8250. DOI:10.3390/ijms25158250
52. Wallace TC, Bultman S, D’Adamo C, et al. Personalized nutrition in disrupting cancer—Proceedings from the 2017 American College of Nutrition Annual Meeting. J Am Coll Nutr. 2019;38(1):1-14. DOI:10.1080/07315724.2018.1500499
53. Greathouse KL, Wyatt M, Johnson AJ, et al. Diet-microbiome interactions in cancer treatment: Opportunities and challenges for precision nutrition in cancer. Neoplasia. 2022;29:100800. DOI:10.1016/j.neo.2022.100800
54. Lagoumintzis G, Patrinos GP. Triangulating nutrigenomics, metabolomics and microbiomics toward personalized nutrition and healthy living. Human Genomics. 2023;17(1):109. DOI:10.1186/s40246-023-00561-w
55. Schemczssen-Graeff Z, Pileggi M. Probiotics and live biotherapeutic products aiming at cancer mitigation and patient recover. Front Genet. 2022;13:921972. DOI:10.3389/fgene.2022.921972
56. Che S, Men Y. Synthetic microbial consortia for biosynthesis and biodegradation: promises and challenges. J Ind Microbiol Biotechnol. 2019;46(9-10):1343-58. DOI:10.1007/s10295-019-02211-4
57. Van der Lelie D, Oka A, Taghavi S, et al. Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis. Nat Commun. 2021;12(1):3105. DOI:10.1038/s41467-021-23460-x
58. Kylilis N, Tuza ZA, Stan GB, Polizzi KM. Tools for engineering coordinated system behaviour in synthetic microbial consortia. Nat Commun. 2018;9(1):2677. DOI:10.1038/s41467-018-05046-2
59. Cordaillat-Simmons M, Rouanet A, Pot B. Live biotherapeutic products: the importance of a defined regulatory framework. Exp Mol Med. 2020;52(9):1397-406. DOI:10.1038/s12276-020-0437-6
60. Rouanet A, Bolca S, Bru A, et al. Live biotherapeutic products, a road map for safety assessment. Front Med (Lausanne). 2020;7:237. DOI:10.3389/fmed.2020.00237
61. Lim ECN, Lim CED. Microbiome-Targeted Therapies in Gastrointestinal Diseases: Clinical Evidence and Emerging Innovations. Acta Microbiologica Hellenica. 2025;70(3):36. DOI:10.3390/amh70030036
62. Nowicka A, Tomczak H, Szałek E, et al. Microbial Crosstalk with Therapy: Pharmacomicrobiomics in AML-One Step Closer to Personalized Medicine. Biomedicines. 2025;13(7):1761. DOI:10.3390/biomedicines13071761
2. Masetti R, Muratore E, Leardini D, et al. Gut microbiome in pediatric acute leukemia: from predisposition to cure. Blood Adv. 2021;5(22):4619-29. DOI:10.1182/bloodadvances.2021005129
3. Антошин М.М., Румянцев С.А., Бельмер С.В. Кишечная микробиота: общие представления и значение при остром лимфобластном лейкозе у детей (обзор литературы). Трудный пациент. 2018;16(8-):49-53 [Antoshin MM, Rumyantsev SA, Belmer SV. Intestinal microbiota: general concepts and significance in acute lymphoblastic leukemia in children (literature review). Trudnyi Patsient. 2018;16(8-9):49-53]. DOI:10.24411/2074-1995-2018-10009
4. Oldenburg M, Rüchel N, Janssen S, et al. The Microbiome in Childhood Acute Lymphoblastic Leukemia. Cancers (Basel). 2021;13(19):4947. DOI:10.3390/cancers13194947
5. Peppas I, Ford AM, Furness CL, Greaves MF. Gut microbiome immaturity and childhood acute lymphoblastic leukaemia. Nat Rev Cancer. 2023;23(8):565-76. DOI:10.1038/s41568-023-00584-4
6. Nycz BT, Dominguez SR, Friedman D, et al. Evaluation of bloodstream infections, Clostridium difficile infections, and gut microbiota in pediatric oncology patients. PLoS One. 2018;13(1):e0191232. DOI:10.1371/journal.pone.0191232
7. Голощапов О.В., Чуракина Д.В., Кучер М.А., и др. Трансплантация фекальной микробиоты при критическом состоянии пациентов в онкогематологической практике. Вестник анестезиологии и реаниматологии. 2019;16(3):63-73 [Goloshchapov OV, Churakina DV, Kucher MA, et al. Fecal microbiota transplantation in critical condition of patients in oncohematological practice. Bulletin of Anesthesiology and Resuscitation. 2019;16(3):63-73 (in Russian)]. DOI:10.21292/2078-5658-2019-16-3-63-73
8. Chrysostomou D, Roberts LA, Marchesi JR, Kinross JM. Gut microbiota modulation of efficacy and toxicity of cancer chemotherapy and immunotherapy. Gastroenterology. 2023;164(2):198-213. DOI:10.1053/j.gastro.2022.10.018
9. Олехнович Е.И., Манолов А.И., Павленко А.В., и др. Влияние микробиома кишечника на эффективность противоопухолевой иммунотерапии. Биомедицинская химия. 2020;66(1):54-63 [Olekhnovich EI, Manolov AI, Pavlenko AV, et al. Influence of gut microbiome on the efficacy of antitumor immunotherapy. Biomed Khim. 2020;66(1):54-63 (in Russian)]. DOI:10.18097/PBMC20206601054
10. Bellone M, Brevi A, Huber S. Microbiota-propelled T helper 17 cells in inflammatory diseases and cancer. Microbiol Mol Biol Rev. 2020;84(2):e00064-19. DOI:10.1128/mmbr.00064-19
11. Mahdy MS, Azmy AF, Dishisha T, et al. Irinotecan-gut microbiota interactions and the capability of probiotics to mitigate Irinotecan-associated toxicity. BMC Microbiol. 2023;23(1):53. DOI:10.1186/s12866-023-02791-3
12. Zeng Y, Shi Q, Liu X, et al. Dynamic gut microbiota changes in patients with advanced malignancies experiencing secondary resistance to immune checkpoint inhibitors and immune-related adverse events. Front Oncol. 2023;13:1144534. DOI:10.3389/fonc.2023.1144534
13. Ni Y, Lohinai Z, Heshiki Y, et al. Distinct composition and metabolic functions of human gut microbiota are associated with cachexia in lung cancer patients. The ISME Journal. 2021;15(11):3207-20. DOI:10.1038/s41396-021-00998-8
14. Nguyen SM, Tran HT, Long J, et al. Gut microbiome in association with chemotherapy-induced toxicities among patients with breast cancer. Cancer. 2024;130(11):2014-30. DOI:10.1002/cncr.35229
15. Giromini C, Baldi A, Rebucci R, et al. Role of Short Chain Fatty Acids to Counteract Inflammatory Stress and Mucus Production in Human Intestinal HT29-MTX-E12 Cells. Foods. 2022;11(13):1983. DOI:10.3390/foods11131983
16. Cazzaniga M, Cardinali M, Di Pierro F, et al. The Potential Role of Probiotics, Especially Butyrate Producers, in the Management of Gastrointestinal Mucositis Induced by Oncologic Chemo-Radiotherapy. Int J Mol Sci. 2024;25(4):2306. DOI:10.3390/ijms25042306
17. Mendes I, Vale N. Overcoming Microbiome-Acquired Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma. Biomedicines. 2024;12(1):227. DOI:10.3390/biomedicines12010227
18. Yin B, Wang X, Yuan F, et al. Research progress on the effect of gut and tumor microbiota on antitumor efficacy and adverse effects of chemotherapy drugs. Front Microbiol. 2022;13:899111. DOI:10.3389/fmicb.2022.899111
19. Adel M, Khedr RA, Sayed AA, et al. Changes in Gut Microbial Diversity and Correlation with Clinical Outcome in Children with Acute Myeloid Leukemia Receiving Induction Chemotherapy. Children (Basel). 2025;12(9):1176. DOI:10.3390/children12091176
20. D’Amico F, Biagi E, Rampelli S, et al. Enteral Nutrition in Pediatric Patients Undergoing Hematopoietic SCT Promotes the Recovery of Gut Microbiome Homeostasis. Nutrients. 2019;11(12):2958. DOI:10.3390/nu11122958
21. Vazquez X, Lumbreras-Iglesias P, Rodicio MR, et al. Study of the intestinal microbiota composition and the effect of treatment with intensive chemotherapy in patients recovered from acute leukemia. Sci Rep. 2024;14(1):5585. DOI:10.1038/s41598-024-56054-w
22. Salvestrini V, Conti G, D'Amico F, et al. Gut Microbiome as a potential marker of hematologic recovery following induction therapy in acute myeloid leukemia patients. Cancer Med. 2025;14(3):e70501. DOI:10.1002/cam4.70501
23. Immonen E, Paulamäki L, Piippo H, et al. Oral microbiome diversity and composition before and after chemotherapy treatment in pediatric oncology patients. BMC Oral Health. 2025;25(1):981. DOI:10.1186/s12903-025-06405-4
24. Guarana M, Nucci M, Nouer SA. Shock and early death in hematologic patients with febrile neutropenia. Antimicrob Agents Chemother. 2019;63(11):e01250-19. DOI:10.1128/aac.01250-19
25. Song A, Shen N, Gan C, et al. Exploration of the relationship between intestinal flora changes and gut acute graft-versus-host disease after hematopoietic stem cell transplantation. Transl Pediatr. 2021;10(2):283-95. DOI:10.21037/tp-20-208
26. Chua LL, Rajasuriar R, Lim YA, et al. Temporal changes in gut microbiota profile in children with acute lymphoblastic leukemia prior to commencement-, during-, and post-cessation of chemotherapy. BMC Cancer. 2020;20(1):151. DOI:10.1186/s12885-020-6654-5
27. Margolis EB, Alfaro GM, Sun Y, et al. Microbiota predict infections and acute graft-versus-host disease after pediatric allogeneic hematopoietic stem cell transplantation. J Infect Dis. 2023;228(5):627-36. DOI:10.1093/infdis/jiad190
28. Biagi E, Zama D, Rampelli S, et al. Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders. BMC Med Genomics. 2019;12(1):49. DOI:10.1186/s12920-019-0494-7
29. Sayin S, Rosener B, Li CG, et al. Evolved bacterial resistance to the chemotherapy gemcitabine modulates its efficacy in co-cultured cancer cells. eLife. 2023;12:e83140. DOI:10.7554/eLife.83140
30. Xu G, Jiang Y, Sun C, et al. Role of Oral Bacteria in Mediating Gemcitabine Resistance in Pancreatic Cancer. Biomolecules. 2025;15(7):1018. DOI:10.3390/biom15071018
31. Meade S, Kiow J, Massaro C, et al. Gut microbiome-associated predictors as biomarkers of response to advanced therapies in inflammatory bowel disease: a systematic review. Gut Microbes. 2023;15(2):2287073. DOI:10.1080/19490976.2023.2287073
32. He Y, Fu L, Li Y, et al. Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8+ T cell immunity. Cell Metabolism. 2021;33(5):988-1000. DOI:10.1016/j.cmet.2021.03.002
33. Павлова С.И. Роль микробиоты и флавоноидов в поддержании баланса хелперных и регуляторных т-лимфоцитов, ассоциированных с иммунным барьером кишечника. Вопросы питания. 2024;93(1):22-32 [Pavlova SI. The role of microbiota and flavonoids in maintaining the balance of helper and regulatory T-lymphocytes associated with the intestinal immune barrier. Voprosy Pitaniia. 2024;93(1):22-32 (in Russian)]. DOI:10.33029/0042-8833-2024-93-1-22-32
34. Anderson R, Theron AJ, Rapoport BL. Immunopathogenesis of immune checkpoint inhibitor-related adverse events: roles of the intestinal microbiome and Th17 cells. Front Immunol. 2019;10:2254. DOI:10.3389/fimmu.2019.02254
35. Pötgens SA, Lecop S, Havelange V, et al. Gut microbiota alterations induced by intensive chemotherapy in acute myeloid leukaemia patients are associated with gut barrier dysfunction and body weight loss. Clin Nutr. 2023;42(11):2214-28. DOI:10.1016/j.clnu.2023.09.021
36. Vicente-Dueñas C, Janssen S, Oldenburg M, et al. An intact gut microbiome protects genetically predisposed mice against leukemia. Blood. 2020;136(18):2003-17. DOI:10.1182/blood.2019004381
37. Yang B, Li W, Shi J. Preventive effect of probiotics on oral mucositis induced by anticancer therapy: a systematic review and meta-analysis of randomized controlled trials. BMC Oral Health. 2024;24(1):1159. DOI:10.1186/s12903-024-04955-7
38. Pedretti L, Leardini D, Muratore E, et al. Managing the Risk of Foodborne Infections in Pediatric Patients with Cancer: Is the Neutropenic Diet Still an Option? Nutrients. 2024;16(7):966. DOI:10.3390/nu16070966
39. Simiakova M, Bielik V. The pros and cons of probiotic use in pediatric oncology patients following treatment for acute lymphoblastic leukemia. Front Pediatr. 2024;12:1427185. DOI:10.3389/fped.2024.1427185
40. Diorio C, Robinson PD, Ammann RA, et al. Guideline for the management of clostridium difficile infection in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation recipients. J Clin Oncol. 2018;36(31):3162-71. DOI:10.1200/JCO.18.00407
41. Zhou S, Martin M, Powell C, et al. How to maintain a healthy gut microbiome in children with cancer? Gut microbiome association with diet in children with solid tumors postchemotherapy. OMICS. 2022;26(4):236-45. DOI:10.1089/omi.2022.0002
42. Gallotti B, Galvao I, Leles G, et al. Effects of dietary fibre intake in chemotherapy-induced mucositis in murine model. Br J Nutr. 2021;126(6):853-64. DOI:10.1017/S0007114520004924
43. Jamal R, Messaoudene M, de Figuieredo M, Routy B. Future indications and clinical management for fecal microbiota transplantation (FMT) in immuno-oncology. Semin Immunol. 2023;67:101754. DOI:10.1016/j.smim.2023.101754
44. Chen D, Wu J, Jin D, et al. Fecal microbiota transplantation in cancer management: Current status and perspectives. Int J Cancer. 2019;145(8):2021-31. DOI:10.1002/ijc.32003
45. Guo Z, He M, Shao L, et al. The role of fecal microbiota transplantation in the treatment of acute graft-versus-host disease. J Cancer Res Ther. 2024;20(7):1964-73. DOI:10.4103/jcrt.jcrt_33_24
46. Henig I, Yehudai-Ofir D, Zuckerman T. The clinical role of the gut microbiome and fecal microbiota transplantation in allogeneic stem cell transplantation. Haematologica. 2021;106(4):933-46. DOI:10.3324/haematol.2020.247395
47. Голощапов О.В., Кучер М.А., Моисеев И.С., и др. Трансплантация фекальной микробиоты у пациентов после аллогенной трансплантации гемопоэтических стволовых клеток. Клеточная терапия и трансплантация. 2018;7(3):56-7 [Goloshchapov OV, Kucher MA, Moiseev IS, et al. Fecal microbiota transplantation in patients after allogeneic hematopoietic stem cell transplantation. Cell Therapy and Transplantation. 2018;7(3):56-7 (in Russian)]. DOI:10.21292/2078-5658-2019-16-3-63-73
48. Prayag PS. Patwardhan SA, Ajapuje PS, et al. Fecal Microbiota Transplantation for Clostridium difficile-associated Diarrhea in Hematopoietic Stem Cell Transplant Recipients: A Single-center Experience from a Tertiary Center in India. Indian J Crit Care Med. 2024;28(2):106-10. DOI:10.5005/jp-journals-10071-24607
49. Bou Zerdan M, Niforatos S, Nasr S, et al. Fecal Microbiota Transplant for Hematologic and Oncologic Diseases: Principle and Practice. Cancers (Basel). 2022;14(3):691. DOI:10.3390/cancers14030691
50. Zhou S, Martin M, Powell C, et al. Associations between Dietary Intakes and the Gut Microbiome in Children with Solid Tumors after Chemotherapy and Healthy Controls. Authorea Preprints. 2021;(2). DOI:10.22541/au.162526069.90949263/v1
51. Munteanu C, Schwartz B. Interactions between Dietary Antioxidants, Dietary Fiber and the Gut Microbiome: Their Putative Role in Inflammation and Cancer. Int J Mol Sci. 2024;25(15):8250. DOI:10.3390/ijms25158250
52. Wallace TC, Bultman S, D’Adamo C, et al. Personalized nutrition in disrupting cancer—Proceedings from the 2017 American College of Nutrition Annual Meeting. J Am Coll Nutr. 2019;38(1):1-14. DOI:10.1080/07315724.2018.1500499
53. Greathouse KL, Wyatt M, Johnson AJ, et al. Diet-microbiome interactions in cancer treatment: Opportunities and challenges for precision nutrition in cancer. Neoplasia. 2022;29:100800. DOI:10.1016/j.neo.2022.100800
54. Lagoumintzis G, Patrinos GP. Triangulating nutrigenomics, metabolomics and microbiomics toward personalized nutrition and healthy living. Human Genomics. 2023;17(1):109. DOI:10.1186/s40246-023-00561-w
55. Schemczssen-Graeff Z, Pileggi M. Probiotics and live biotherapeutic products aiming at cancer mitigation and patient recover. Front Genet. 2022;13:921972. DOI:10.3389/fgene.2022.921972
56. Che S, Men Y. Synthetic microbial consortia for biosynthesis and biodegradation: promises and challenges. J Ind Microbiol Biotechnol. 2019;46(9-10):1343-58. DOI:10.1007/s10295-019-02211-4
57. Van der Lelie D, Oka A, Taghavi S, et al. Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis. Nat Commun. 2021;12(1):3105. DOI:10.1038/s41467-021-23460-x
58. Kylilis N, Tuza ZA, Stan GB, Polizzi KM. Tools for engineering coordinated system behaviour in synthetic microbial consortia. Nat Commun. 2018;9(1):2677. DOI:10.1038/s41467-018-05046-2
59. Cordaillat-Simmons M, Rouanet A, Pot B. Live biotherapeutic products: the importance of a defined regulatory framework. Exp Mol Med. 2020;52(9):1397-406. DOI:10.1038/s12276-020-0437-6
60. Rouanet A, Bolca S, Bru A, et al. Live biotherapeutic products, a road map for safety assessment. Front Med (Lausanne). 2020;7:237. DOI:10.3389/fmed.2020.00237
61. Lim ECN, Lim CED. Microbiome-Targeted Therapies in Gastrointestinal Diseases: Clinical Evidence and Emerging Innovations. Acta Microbiologica Hellenica. 2025;70(3):36. DOI:10.3390/amh70030036
62. Nowicka A, Tomczak H, Szałek E, et al. Microbial Crosstalk with Therapy: Pharmacomicrobiomics in AML-One Step Closer to Personalized Medicine. Biomedicines. 2025;13(7):1761. DOI:10.3390/biomedicines13071761
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39. Simiakova M, Bielik V. The pros and cons of probiotic use in pediatric oncology patients following treatment for acute lymphoblastic leukemia. Front Pediatr. 2024;12:1427185. DOI:10.3389/fped.2024.1427185
40. Diorio C, Robinson PD, Ammann RA, et al. Guideline for the management of clostridium difficile infection in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation recipients. J Clin Oncol. 2018;36(31):3162-71. DOI:10.1200/JCO.18.00407
41. Zhou S, Martin M, Powell C, et al. How to maintain a healthy gut microbiome in children with cancer? Gut microbiome association with diet in children with solid tumors postchemotherapy. OMICS. 2022;26(4):236-45. DOI:10.1089/omi.2022.0002
42. Gallotti B, Galvao I, Leles G, et al. Effects of dietary fibre intake in chemotherapy-induced mucositis in murine model. Br J Nutr. 2021;126(6):853-64. DOI:10.1017/S0007114520004924
43. Jamal R, Messaoudene M, de Figuieredo M, Routy B. Future indications and clinical management for fecal microbiota transplantation (FMT) in immuno-oncology. Semin Immunol. 2023;67:101754. DOI:10.1016/j.smim.2023.101754
44. Chen D, Wu J, Jin D, et al. Fecal microbiota transplantation in cancer management: Current status and perspectives. Int J Cancer. 2019;145(8):2021-31. DOI:10.1002/ijc.32003
45. Guo Z, He M, Shao L, et al. The role of fecal microbiota transplantation in the treatment of acute graft-versus-host disease. J Cancer Res Ther. 2024;20(7):1964-73. DOI:10.4103/jcrt.jcrt_33_24
46. Henig I, Yehudai-Ofir D, Zuckerman T. The clinical role of the gut microbiome and fecal microbiota transplantation in allogeneic stem cell transplantation. Haematologica. 2021;106(4):933-46. DOI:10.3324/haematol.2020.247395
47. Goloshchapov OV, Kucher MA, Moiseev IS, et al. Fecal microbiota transplantation in patients after allogeneic hematopoietic stem cell transplantation. Cell Therapy and Transplantation. 2018;7(3):56-7 (in Russian). DOI:10.21292/2078-5658-2019-16-3-63-73
48. Prayag PS. Patwardhan SA, Ajapuje PS, et al. Fecal Microbiota Transplantation for Clostridium difficile-associated Diarrhea in Hematopoietic Stem Cell Transplant Recipients: A Single-center Experience from a Tertiary Center in India. Indian J Crit Care Med. 2024;28(2):106-10. DOI:10.5005/jp-journals-10071-24607
49. Bou Zerdan M, Niforatos S, Nasr S, et al. Fecal Microbiota Transplant for Hematologic and Oncologic Diseases: Principle and Practice. Cancers (Basel). 2022;14(3):691. DOI:10.3390/cancers14030691
50. Zhou S, Martin M, Powell C, et al. Associations between Dietary Intakes and the Gut Microbiome in Children with Solid Tumors after Chemotherapy and Healthy Controls. Authorea Preprints. 2021;(2). DOI:10.22541/au.162526069.90949263/v1
51. Munteanu C, Schwartz B. Interactions between Dietary Antioxidants, Dietary Fiber and the Gut Microbiome: Their Putative Role in Inflammation and Cancer. Int J Mol Sci. 2024;25(15):8250. DOI:10.3390/ijms25158250
52. Wallace TC, Bultman S, D’Adamo C, et al. Personalized nutrition in disrupting cancer—Proceedings from the 2017 American College of Nutrition Annual Meeting. J Am Coll Nutr. 2019;38(1):1-14. DOI:10.1080/07315724.2018.1500499
53. Greathouse KL, Wyatt M, Johnson AJ, et al. Diet-microbiome interactions in cancer treatment: Opportunities and challenges for precision nutrition in cancer. Neoplasia. 2022;29:100800. DOI:10.1016/j.neo.2022.100800
54. Lagoumintzis G, Patrinos GP. Triangulating nutrigenomics, metabolomics and microbiomics toward personalized nutrition and healthy living. Human Genomics. 2023;17(1):109. DOI:10.1186/s40246-023-00561-w
55. Schemczssen-Graeff Z, Pileggi M. Probiotics and live biotherapeutic products aiming at cancer mitigation and patient recover. Front Genet. 2022;13:921972. DOI:10.3389/fgene.2022.921972
56. Che S, Men Y. Synthetic microbial consortia for biosynthesis and biodegradation: promises and challenges. J Ind Microbiol Biotechnol. 2019;46(9-10):1343-58. DOI:10.1007/s10295-019-02211-4
57. Van der Lelie D, Oka A, Taghavi S, et al. Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis. Nat Commun. 2021;12(1):3105. DOI:10.1038/s41467-021-23460-x
58. Kylilis N, Tuza ZA, Stan GB, Polizzi KM. Tools for engineering coordinated system behaviour in synthetic microbial consortia. Nat Commun. 2018;9(1):2677. DOI:10.1038/s41467-018-05046-2
59. Cordaillat-Simmons M, Rouanet A, Pot B. Live biotherapeutic products: the importance of a defined regulatory framework. Exp Mol Med. 2020;52(9):1397-406. DOI:10.1038/s12276-020-0437-6
60. Rouanet A, Bolca S, Bru A, et al. Live biotherapeutic products, a road map for safety assessment. Front Med (Lausanne). 2020;7:237. DOI:10.3389/fmed.2020.00237
61. Lim ECN, Lim CED. Microbiome-Targeted Therapies in Gastrointestinal Diseases: Clinical Evidence and Emerging Innovations. Acta Microbiologica Hellenica. 2025;70(3):36. DOI:10.3390/amh70030036
62. Nowicka A, Tomczak H, Szałek E, et al. Microbial Crosstalk with Therapy: Pharmacomicrobiomics in AML-One Step Closer to Personalized Medicine. Biomedicines. 2025;13(7):1761. DOI:10.3390/biomedicines13071761
Авторы
А.А. Муртазин*, А.Х. Исламгулов, В.А. Малиевский
ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России, Уфа, Российская Федерация
*beep.boy.official@gmail.com
Bashkir State Medical University, Ufa, Russian Federation
*beep.boy.official@gmail.com
ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России, Уфа, Российская Федерация
*beep.boy.official@gmail.com
________________________________________________
Bashkir State Medical University, Ufa, Russian Federation
*beep.boy.official@gmail.com
Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.