Modern view on the role of microbiota in chemotherapy in children
- Authors: Islamgulov A.C.1, Murtazin A.A.1, Malievsky V.A.1, Kalmetyeva L.R.1, Proligina D.D.1, Davletbaeva G.A.1, Gazizullina G.R.1
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Affiliations:
- Bashkir State Medical University
- Issue: Vol 31, No 1 (2026)
- Pages: 42-53
- Section: Reviews
- Submitted: 20.11.2025
- Accepted: 09.01.2026
- Published: 04.03.2026
- URL: https://rjonco.com/1028-9984/article/view/696672
- DOI: https://doi.org/10.17816/onco696672
- EDN: https://elibrary.ru/NPCASS
- ID: 696672
Cite item
Abstract
The gut microbiota (GM) plays an important role in modulating the effectiveness and toxicity of chemotherapy (CT) in children with oncological diseases. In this review, the authors analyzed and systematized current data on the role of GM in the tolerability and effectiveness of therapy in acute leukemias and demonstrated the interrelation between CT and GM. Chemotherapy causes changes in GM: it reduces the number of different bacterial species, decreases the number of beneficial species, and increases the abundance of opportunistic bacteria, which increases the risk of complications such as mucositis, febrile neutropenia, and sepsis. The reciprocal effect of GM on CT occurs through direct impact on the metabolism of cytostatics and systemic immunomodulation. One of the important mechanisms of GM influence is the formation of short-chain fatty acids, particularly butyrate, which enhances the function of cytotoxic T-lymphocytes, induces apoptosis of tumor cells, and supports normal intestinal function. Promising directions for dysbiosis correction are probiotics, prebiotics, and fecal microbiota transplantation, which shows high effectiveness in steroid-resistant graft-versus-host disease. Integration of microbiome biomarker research into prognostic models and the use of multi-omics technologies provide an opportunity for the development of individualized treatment approaches. Based on the available data, GM is an important factor in the effective delivery of CT in children, and methods of its modification have high potential for improving survival and quality of life in these patients, which requires further confirmation in randomized controlled trials.
Full Text
About the authors
Almaz Ch. Islamgulov
Bashkir State Medical University
Author for correspondence.
Email: aslmaz2000@gmail.com
ORCID iD: 0000-0003-0567-7515
SPIN-code: 8701-3486
Russian Federation, 98 Stepan Kuvykin st, Ufa, 450092
Azat A. Murtazin
Bashkir State Medical University
Email: beep.boy.official@gmail.com
ORCID iD: 0009-0001-4491-9495
SPIN-code: 2792-6429
Russian Federation, 98 Stepan Kuvykin st, Ufa, 450092
Viktor A. Malievsky
Bashkir State Medical University
Email: malievsky@list.ru
ORCID iD: 0000-0003-0522-7442
SPIN-code: 4429-2910
MD, Dr. Sci. (Medicine), Professor
Russian Federation, 98 Stepan Kuvykin st, Ufa, 450092Linara R. Kalmetyeva
Bashkir State Medical University
Email: l_kalmetieva@mail.ru
ORCID iD: 0000-0003-1866-0640
SPIN-code: 3359-1255
MD, Cand. Sci. (Medicine), Assistant Professor
Russian Federation, 98 Stepan Kuvykin st, Ufa, 450092Dilyara D. Proligina
Bashkir State Medical University
Email: dil.proligina@yandex.ru
ORCID iD: 0000-0002-5797-4370
MD, Cand. Sci. (Medicine)
Russian Federation, 98 Stepan Kuvykin st, Ufa, 450092Gulchat A. Davletbaeva
Bashkir State Medical University
Email: davgulufa@mail.ru
ORCID iD: 0000-0002-6468-9172
MD, Cand. Sci. (Medicine)
Russian Federation, 98 Stepan Kuvykin st, Ufa, 450092Gulnara R. Gazizullina
Bashkir State Medical University
Email: akhmetova.29@bk.ru
ORCID iD: 0009-0005-2508-7901
SPIN-code: 2512-9030
Russian Federation, 98 Stepan Kuvykin st, Ufa, 450092
References
- Susuleva NA, Ryabukhina YuE, Zaynalova PA, et al. Problems of pediatric oncology. Oncological alertness. Consilium Medicum. 2023;25(8):497–504. doi: 10.26442/20751753.2023.8.202336 EDN: WBCJAE
- Zong Y, Zhou Y, Liao B, et al. The interaction between the microbiome and tumors. Front Cell Infect Microbiol. 2021;11:673724. doi: 10.3389/fcimb.2021.673724 EDN: ROXAAA
- Wen Y, Jin R, Chen H. Interactions Between Gut Microbiota and Acute Childhood Leukemia. Front Microbiol. 2019;10:1300. doi: 10.3389/fmicb.2019.01300
- Zhou Y, Zhou C, Zhang A. Gut microbiota in acute leukemia: Current evidence and future directions. Front Microbiol. 2022;13:1045497. doi: 10.3389/fmicb.2022.1045497
- Bukharin OV, Perunova NB. The role of microbiota in the regulation of human body homeostasis during infection. Journal of Microbiology, Epidemiology and Immunobiology. 2020;(5):458–467. doi: 10.36233/0372-9311-2020-97-5-8 EDN: BDUJFY
- Hueso T, Ekpe K, Mayeur C, et al. Impact and consequences of intensive chemotherapy on intestinal barrier and microbiota in acute myeloid leukemia: the role of mucosal strengthening. Gut Microbes. 2020;12(1). doi: 10.1080/19490976.2020.1800897 EDN: NLHKMD
- Garg S, Sharma N, Bharmjeet, Das A. Unraveling the intricate relationship: Influence of microbiome on the host immune system in carcinogenesis. Cancer Rep. 2023;6(11):e1892. doi: 10.1002/cnr2.1892 EDN: OPNJDW
- Bose M, Mukherjee P. Role of microbiome in modulating immune responses in cancer. Mediators Inflamm. 2019;2019:4107917. doi: 10.1155/2019/4107917
- Sági V, Makra N, Csoszánszki N, et al. The Influence of the Gut Microbiome in Paediatric Cancer Origin and Treatment. Antibiotics. 2022;11(11):1521. doi: 10.3390/antibiotics11111521 EDN: BRGCFI
- Ma T, Chen Y, Li LJ, Zhang LS. Opportunities and Challenges for Gut Microbiota in Acute Leukemia. Front Oncol. 2021;11:692951. doi: 10.3389/fonc.2021.692951 EDN: FXYIDN
- Dedikova OV, Zakharova IN, Kuchina AE, et al. Formation of infant gut microbiota depending on the mode of delivery: long-term consequences and correction options. Pediatrics. Consilium Medicum. 2023;(1):25–29. doi: 10.26442/26586630.2023.1.202092 EDN: AQBKCL
- Lucafò M, Franzin M, Lagatolla C, et al. Emerging insights on the interaction between anticancer and immunosuppressant drugs and intestinal microbiota in pediatric patients. Clin Transl Sci. 2020;13(2):238–259. doi: 10.1111/cts.12722
- Priputnevich TV, Isaeva EL, Muravyeva VV, et al. Formation of gut microbiota in full-term and late preterm infants born spontaneously and by cesarean section. Neonatology: News, Opinions, Training. 2023;11(1):42–56. doi: 10.33029/2308-2402-2023-11-1-42-56 EDN: DXEIBL
- Marcotte EL, Richardson MR, Roesler MA, Spector LG. Cesarean delivery and risk of infant Leukemia: a report from the children’s oncology group. Cancer Epidemiol Biomarkers Prev. 2018;27(4):473–478. doi: 10.1158/1055-9965.EPI-17-0778
- Gudnadottir U, Fransson E, Ljungman G, et al. Prenatal and Early Childhood Exposure to Proton Pump Inhibitors and Antibiotics and the Risk of Childhood Cancer: A Nationwide Population-Based Cohort Study. Drug Saf. 2025;48:375–388. doi: 10.1007/s40264-024-01500-x EDN: UPVGPO
- Aris IM, Lin PI, Rifas-Shiman SL, et al. Association of early antibiotic exposure with childhood body mass index trajectory milestones. JAMA Netw Open. 2021;4(12):e2116581. doi: 10.1001/jamanetworkopen.2021.16581 EDN: KVDINE
- Koebnick C, Tartof SY, Sidell MA, et al. Effect of in-utero antibiotic exposure on childhood outcomes: methods and baseline data of the Fetal Antibiotic EXposure (FAX) cohort study. JMIR Res Protoc. 2019;8(7):e12065. doi: 10.2196/12065
- Lazar V, Ditu LM, Pircalabioru GG, et al. Aspects of gut microbiota and immune system interactions in infectious diseases, immunopathology, and cancer. Front Immunol. 2018;9:1830. doi: 10.3389/fimmu.2018.01830
- Gallant R, Reza S, Wiemels JL, Greaves M. Microbiome and pediatric leukemia, diabetes, and allergies: Systematic review and meta-analysis. PLoS One. 2025;20(5):e0324167. doi: 10.1371/journal.pone.0324167 EDN: KNQCPJ
- Vivarelli S, Salemi R, Candido S, et al. Gut Microbiota and Cancer: From Pathogenesis to Therapy. Cancers. 2019;11(1):38. doi: 10.3390/cancers11010038 EDN: EJAJEK
- Maddern AS, Coller JK, Bowen JM, et al. The Association between the Gut Microbiome and Development and Progression of Cancer Treatment Adverse Effects. Cancers. 2023;15(17):4301. doi: 10.3390/cancers15174301 EDN: FFUSNH
- Wei L, Wen X-S, Xian CJ. Chemotherapy-Induced Intestinal Microbiota Dysbiosis Impairs Mucosal Homeostasis by Modulating Toll-like Receptor Signaling Pathways. Int J Mol Sci. 2021;22(17):9474. doi: 10.3390/ijms22179474 EDN: JHBPAG
- He Z, Xie H, Xu H, et al. Chemotherapy-induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin-10 from macrophages. Gut Microbes. 2024;16(1). doi: 10.1080/19490976.2024.2319511 EDN: WNSLWL
- Sougiannis AT, VanderVeen BN, Davis JM, Fan D, Murphy EA. Understanding chemotherapy-induced intestinal mucositis and strategies to improve gut resilience. Am J Physiol Gastrointest Liver Physiol. 2021;320(5):G712–G719. doi: 10.1152/ajpgi.00380.2020 EDN: USCSNG
- Jiang W, Wu Y, He X, et al. Important Role of Intestinal Microbiota in Chemotherapy-induced Diarrhea and Therapeutics. J Cancer. 2025;16(2):648–659. doi: 10.7150/jca.99421 EDN: FNFNTA
- Dunn KA, MacDonald T, Rodrigues GJ, et al. Antibiotic and antifungal use in pediatric leukemia and lymphoma patients are associated with increasing opportunistic pathogens and decreasing bacteria responsible for activities that enhance colonic defense. Front Cell Infect Microbiol. 2022;12:924707. doi: 10.3389/fcimb.2022.924707 EDN: FOQCJF
- Sun M, Tang D, Jia J, et al. The role of the gut microbiota in infectious complications during immunochemotherapy for diffuse large B-cell lymphoma. BMC Cancer. 2024;24:1570. doi: 10.1186/s12885-024-13344-w EDN: AQKRDF
- Mannavola CM, De Maio F, Marra J, et al. Bloodstream infection by Lactobacillus rhamnosus in a haematology patient: why metagenomics can make the difference. Gut Pathog. 2025;17:47. doi: 10.1186/s13099-025-00722-3 EDN: GFBKJK
- Ziemons J, Hillege LE, Aarnoutse R, et al. Prebiotic fibre mixtures counteract the manifestation of gut microbial dysbiosis induced by the chemotherapeutic 5-Fluorouracil (5-FU) in a validated in vitro model of the colon. BMC Microbiol. 2024;24:222. doi: 10.1186/s12866-024-03384-4 EDN: DFUWRP
- Dalal P, Sharma D. Microbe defines the efficacy of chemotherapeutic drug: a complete paradigm. FEMS Microbiol Lett. 2021;368(17). doi: 10.1093/femsle/fnab116 EDN: KPNNAX
- Mafe AN, Büsselberg D. Microbiome Integrity Enhances the Efficacy and Safety of Anticancer Drug. Biomedicines. 2025;13(2):422. doi: 10.3390/biomedicines13020422 EDN: XWKTUG
- Kaźmierczak-Siedlecka K, Bulman N, Ulasiński P, et al. Pharmacomicrobiomics of cell-cycle specific anti-cancer drugs — is it a new perspective for personalized treatment of cancer patients? Gut Microbes. 2023;15(2). doi: 10.1080/19490976.2023.2281017 EDN: ODTFIA
- Li X, Zhang S, Guo G, Han J, Yu J. Gut microbiome in modulating immune checkpoint inhibitors. EBioMedicine. 2022;82. doi: 10.1016/j.ebiom.2022.104163
- Luu M, Riester Z, Baldrich A, et al. Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer. Nat Commun. 2021;12:4077. doi: 10.1038/s41467-021-24331-1 EDN: KFMAGV
- Thome CD, Tausche P, Hohenberger K, et al. Short-chain fatty acids induced lung tumor cell death and increased peripheral blood CD4+ T cells in NSCLC and control patients ex vivo. Front Immunol. 2024;15:1328263. doi: 10.3389/fimmu.2024.1328263 EDN: EVAAUB
- Bachem A, Makhlouf C, Binger KJ, et al. Microbiota-derived short-chain fatty acids promote the memory potential of antigen-activated CD8+ T cells. Immunity. 2019;51(2):285–297. doi: 10.1016/j.immuni.2019.06.002 EDN: IJVABZ
- Dong Y, Zhang K, Wei J, et al. Gut microbiota-derived short-chain fatty acids regulate gastrointestinal tumor immunity: a novel therapeutic strategy? Front Immunol. 2023;14:1158200. doi: 10.3389/fimmu.2023.1158200 EDN: OPTCTX
- Nakkarach A, Foo HL, Song AAL, et al. Anti-cancer and anti-inflammatory effects elicited by short chain fatty acids produced by Escherichia coli isolated from healthy human gut microbiota. Microb Cell Fact. 2021;20:36. doi: 10.1186/s12934-020-01477-z EDN: YHGZAX
- De Pietri S, Weischendorff S, Rathe M, et al. Gastrointestinal barrier integrity and mucosal inflammation as risk factors of blood stream infections in children treated for acute lymphoblastic leukaemia. Int J Cancer. 2023;153(9):1635–1642. doi: 10.1002/ijc.34639 EDN: YOZWCM
- Jin S, Guan T, Wang S, Hu M, Liu X, Huang S, Liu Y. Dioscin Alleviates Cisplatin-Induced Mucositis in Rats by Modulating Gut Microbiota, Enhancing Intestinal Barrier Function and Attenuating TLR4/NF-κB Signaling Cascade. Int J Mol Sci. 2022;23(8):4431. doi: 10.3390/ijms23084431 EDN: DAFFAU
- Yin Q, Li X, Xiong Y, et al. Bletilla oligosaccharides improved 5-fluorouracil-induced intestinal mucositis in mice by activating NF-κB signalling pathway and regulating intestinal microbiota. Front Pharmacol. 2025;16:1526274. doi: 10.3389/fphar.2025.1526274 EDN: MJDMGN
- Kouzu K, Tsujimoto H, Kishi Y, Ueno H, Shinomiya N. Bacterial Translocation in Gastrointestinal Cancers and Cancer Treatment. Biomedicines. 2022;10(2):380. doi: 10.3390/biomedicines10020380 EDN: TKVRBS
- Sardzikova S, Andrijkova K, Svec P, et al. Gut diversity and the resistome as biomarkers of febrile neutropenia outcome in paediatric oncology patients undergoing hematopoietic stem cell transplantation. Sci Rep. 2024;14:5504. doi: 10.1038/s41598-024-56242-8 EDN: TREZBT
- Wang H, Li B, Li A, et al. Characteristics of gut microbiome and prediction of infection in neutropenic children with acute leukemia. Res Sq. 2020. doi: 10.21203/rs.3.rs-61001/v1
- Chen Z, Zhou D, Han S, et al. Hepatotoxicity and the role of the gut-liver axis in rats after oral administration of titanium dioxide nanoparticles. Part Fibre Toxicol. 2019;16:48. doi: 10.1186/s12989-019-0332-2 EDN: GQXKUO
- Li C, Cai C, Wang C, Chen X, Zhang B, Huang Z. Gut microbiota-mediated gut-liver axis: a breakthrough point for understanding and treating liver cancer. Clin Mol Hepatol. 2025;31(2):350–381. doi: 10.3350/cmh.2024.0857 EDN: ODYVBQ
- Brown T, Sykes D, Allen AR. Implications of Breast Cancer Chemotherapy-Induced Inflammation on the Gut, Liver, and Central Nervous System. Biomedicines. 2021;9(2):189. doi: 10.3390/biomedicines9020189 EDN: AFHDGM
- Hemmati MA, Monemi M, Asli S, et al. Using New Technologies to Analyze Gut Microbiota and Predict Cancer Risk. Cells. 2024;13(23):1987. doi: 10.3390/cells13231987 EDN: UZIMTE
- Wu J, Singleton SS, Bhuiyan U, Krammer L, Mazumder R. Multi-omics approaches to studying gastrointestinal microbiome in the context of precision medicine and machine learning. Front Mol Biosci. 2024;10:1337373. doi: 10.3389/fmolb.2023.1337373 EDN: NTQFZG
- Wang H, Zhang Y, Zhou Q, et al. Microbial metagenomic shifts in children with acute lymphoblastic leukaemia during induction therapy and predictive biomarkers for infection. Ann Clin Microbiol Antimicrob. 2024;23:52. doi: 10.1186/s12941-024-00717-z EDN: JYRSOI
- Sørum ME, Boulund U, De Pietri S, et al. Changes in gut microbiota predict neutropenia after induction treatment in childhood acute lymphoblastic leukemia. Blood Adv. 2025;9(7):1508–1521. doi: 10.1182/bloodadvances.2024013986 EDN: FQLYCJ
- Ingham AC, Kielsen K, Mordhorst H, et al. Microbiota long-term dynamics and prediction of acute graft-versus-host disease in pediatric allogeneic stem cell transplantation. Microbiome. 2021;9:148. doi: 10.1186/s40168-021-01100-2 EDN: OFONII
- Barsan V, Xia Y, Klein D, et al. Simultaneous monitoring of disease and microbe dynamics through plasma DNA sequencing in pediatric patients with acute lymphoblastic leukemia. Sci Adv. 2022;8(16):eabj1360. doi: 10.1126/sciadv.abj1360 EDN: YXKDWT
- Bai J, Eldridge R, Houser M, et al. Multi-omics analysis of the gut microbiome and metabolites associated with the psychoneurological symptom cluster in children with cancer receiving chemotherapy. J Transl Med. 2024;22:256. doi: 10.1186/s12967-024-05066-1 EDN: KSXLID
- Morgacheva DA, Dinikina YuV, Toshina YuK, et al. The role of the microbiome in the pathogenesis of infectious and immunological damage to the gastrointestinal tract in children with oncohematological diseases. Oncohematology. 2021;16(2):86–93. doi: 10.17650/1818-8346-2021-16-2-86-93 EDN: VSUSSJ
- Wang C, Segal LN, Hu J, et al. Microbial risk score for capturing microbial characteristics, integrating multi-omics data, and predicting disease risk. Microbiome. 2022;10:121. doi: 10.1186/s40168-022-01310-2 EDN: MMVRSS
- Kulecka M, O’Sullivan J, Fitzgerald R, et al. Combining mucosal microbiome and host multi-omics data shows prognostic potential in paediatric ulcerative colitis. Nat Commun. 2025;16:7157. doi: 10.1038/s41467-025-62533-z EDN: ARJUGV
- Janssens KP, Valete COS, Silva ARAD, Ferman SE. Evaluation of risk stratification strategies in pediatric patients with febrile neutropenia. J Pediatr. 2021;97(3):302–308. doi: 10.1016/j.jped.2020.05.002 EDN: MQDVAB
- Le Ngoc K, Pham TTH, Nguyen TK, Huong PT. Pharmacomicrobiomics in precision cancer therapy: bench to bedside. Front Immunol. 2024;15:1428420. doi: 10.3389/fimmu.2024.1428420 EDN: UMLQFG
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