Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Scientific Reports
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. scientific reports
  3. articles
  4. article
Impact of microbiome-modulating strategies in cancer patients receiving immunotherapy (MSIT): A systematic review and meta-analysis
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 17 March 2026

Impact of microbiome-modulating strategies in cancer patients receiving immunotherapy (MSIT): A systematic review and meta-analysis

  • May Soe Thu1,
  • Ho Bao Chau Le1,2,
  • Nguyen Phuc Duc1,2,
  • Van Hieu Mai3,4,
  • Nina Walker5 &
  • …
  • Nattiya Hirankarn1 

Scientific Reports , Article number:  (2026) Cite this article

  • 921 Accesses

  • 1 Altmetric

  • Metrics details

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Cancer
  • Immunology
  • Microbiology
  • Oncology

Abstract

The gut microbiota influences immune checkpoint inhibitors (ICIs) efficacy. Microbiome-modulating strategies (MMSs), including probiotics, synbiotics, and faecal microbiota transplantation (FMT), have emerged as promising adjuncts, but their clinical impact remains uncertain. We systematically reviewed PubMed, Embase, and CENTRAL to February 2025 for clinical cohorts evaluating MMS in cancer patients receiving ICIs. Thirty-six studies (25 trials/cohorts; n = 2,746) were included. Meta-analyses, and subgroup analyses were performed for efficacy along with microbiome shifts and safety. MMS plus ICIs achieved a pooled objective response rate (ORR) of 40% (95% CI: 31%–49%; I² = 63.4%; p = 0.0003; 95% PI: 15%–72%). Descriptive proportions showed ORR of 45% (95% CI: 32%–58%; I² = 72.5%; p = 0.0058) for probiotics and 33% (95% CI: 22%–48%; I² = 60.7%; p = 0.0064) for FMT; however, these findings are non-comparative and confounded by study differences. Exploratory subgroup signals were noted for probiotics in NSCLC (ORR 55%; 95%CI: 45%–64%; I² = 0%; p = 0.3683) and FMT in melanoma (ORR 39%; 95% CI: 15%–69%; I² = 72.5%; p = 0.0262). Dual ICI regimens showed the highest point estimate for ORR (43%; 95% CI: 17%–73%; I² = 68.5%; p = 0.0747) but increased toxicity. Microbiome analyses revealed enrichment of short-chain fatty acid-producing taxa and Bifidobacterium spp. among responders. Based on a limited pooled sample size (n = 143), MMS-related adverse events were mostly grade 1–2 (42%; 95% CI: 14%–77%, I² = 53.8%, p = 0.0210), with rare severe events (1%). Overall, MMS show promising, though preliminary, hypothesis-generating signals for modulating ICI response. Given high heterogeneity and reliance on early-phase, single-arm trials, the findings underscore urgent need for large, biomarker-driven randomized controlled trials to define optimal interventions and cautiously integrate microbiome modulation into immuno-oncology care.

Similar content being viewed by others

Towards modulating the gut microbiota to enhance the efficacy of immune-checkpoint inhibitors

Article 24 July 2023

Microbiota in cancer: current understandings and future perspectives

Article Open access 02 February 2026

Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma

Article Open access 28 February 2022

Data availability

The data are available as supplementary files.

Abbreviations

CENTRAL:

Cochrane central register of controlled trials

CIs:

Confidence intervals

PRISMA-P:

Preferred reporting items for systematic review and meta-analysis protocols

RCTs:

Randomized controlled trials

US:

United States

References

  1. Siegel, R. L., Miller, K. D., Fuchs, H. E. & Jemal, A. Cancer statistics, 2022. CA. Cancer J. Clin. https://doi.org/10.3322/caac.21708 (2022).

    Google Scholar 

  2. Bagchi, S., Yuan, R. & Engleman, E. G. Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance. Annu. Rev. Pathol. 16 (1), 223–249. https://doi.org/10.1146/annurev-pathol-042020-042741 (2021).

    Google Scholar 

  3. Lao, Y., Shen, D., Zhang, W., He, R. & Jiang, M. Immune checkpoint inhibitors in cancer therapy-how to overcome drug resistance?. Cancers (Basel) https://doi.org/10.3390/cancers14153575 (2022).

    Google Scholar 

  4. Mamdani, H., Matosevic, S., Khalid, A. B., Durm, G. & Jalal, S. I. Immunotherapy in lung cancer: current landscape and future directions. Front. Immunol. 13, 823618. https://doi.org/10.3389/fimmu.2022.823618 (2022).

    Google Scholar 

  5. Dobosz, P., Stępień, M., Golke, A. & Dzieciątkowski, T. Challenges of the immunotherapy: perspectives and limitations of the immune checkpoint inhibitor treatment. Int. J. Mol. Sci. 23 (5), 2847. https://doi.org/10.3390/ijms23052847 (2022).

    Google Scholar 

  6. Hiltbrunner, S. et al. Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype. Nat. Commun. 14 (1), 5154. https://doi.org/10.1038/s41467-023-40745-5 (2023).

    Google Scholar 

  7. Mariniello, A. et al. Primary and Acquired Resistance to Immunotherapy with Checkpoint Inhibitors in NSCLC: From Bedside to Bench and Back. BioDrugs 39 (2), 215–235. https://doi.org/10.1007/s40259-024-00700-2 (2025).

    Google Scholar 

  8. He, R. et al. Dysbiosis and extraintestinal cancers. J. Experimental Clin. Cancer Res. 44 (1), 44. https://doi.org/10.1186/s13046-025-03313-x (2025).

    Google Scholar 

  9. Kumari, S., Srilatha, M. & Nagaraju, G. P. Effect of Gut Dysbiosis on Onset of GI Cancers. Cancers 17 (1), 90 (2025). https://www.mdpi.com/2072-6694/17/1/90

    Google Scholar 

  10. Sarkar, J. et al. Fluctuations in gut microbiome composition during immune checkpoint inhibitor therapy. World J. Oncol. 14 (3), 178. https://doi.org/10.14740/wjon1587 (2023).

    Google Scholar 

  11. Kuziel, G. A. & Rakoff-Nahoum, S. The gut microbiome. Curr. Biol. 32(6), R257–R64. https://doi.org/10.1016/j.cub.2022.02.023 (2022).

    Google Scholar 

  12. Li, Z. et al. Critical role of the gut microbiota in immune responses and cancer immunotherapy. J. Hematol. Oncol. 17(1), 33. https://doi.org/10.1186/s13045-024-01541-w (2024).

    Google Scholar 

  13. Bretto, E., Urpì-Ferreruela, M., Casanova, G. R. & González-Suárez, B. The role of gut microbiota in gastrointestinal immune homeostasis and inflammation: Implications for inflammatory bowel disease. Biomedicines 13(8), 1807 (2025).

    Google Scholar 

  14. Di Vincenzo, F., Del Gaudio, A., Petito, V., Lopetuso, L. R. & Scaldaferri, F. Gut microbiota, intestinal permeability, and systemic inflammation: A narrative review. Intern. Emerg. Med. 19(2), 275–93. https://doi.org/10.1007/s11739-023-03374-w (2024).

    Google Scholar 

  15. Hagihara, M. et al. Clostridium butyricum modulates the microbiome to protect intestinal barrier function in mice with antibiotic-induced dysbiosis. Iscience https://doi.org/10.1016/j.isci.2019.100772 (2020).

    Google Scholar 

  16. Soto Chervin, C. & Gajewski, T. F. Microbiome-based interventions: Therapeutic strategies in cancer immunotherapy. Immuno-Oncol. Technol. 8, 12–20. https://doi.org/10.1016/j.iotech.2020.11.001 (2020).

    Google Scholar 

  17. Ghosh, S., Whitley, C. S., Haribabu, B. & Jala, V. R. Regulation of intestinal barrier function by microbial metabolites. Cell. Mol. Gastroenterol. Hepatol. 11(5), 1463–82. https://doi.org/10.1016/j.jcmgh.2021.02.007 (2021).

    Google Scholar 

  18. Hou, S., Yu, J., Li, Y., Zhao, D. & Zhang, Z. Advances in fecal microbiota transplantation for gut dysbiosis-related diseases. Adv. Sci. 12(13), 2413197. https://doi.org/10.1002/advs.202413197 (2025).

    Google Scholar 

  19. Yang, R., Chen, Z. & Cai, J. Fecal microbiota transplantation: Emerging applications in autoimmune diseases. J. Autoimmun. 141, 103038. https://doi.org/10.1016/j.jaut.2023.103038 (2023).

    Google Scholar 

  20. Zhang, M., Liu, J. & Xia, Q. Role of gut microbiome in cancer immunotherapy: from predictive biomarker to therapeutic target. Experimental Hematol. Oncol. 12 (1), 84. https://doi.org/10.1186/s40164-023-00442-x (2023).

    Google Scholar 

  21. Reunanen, J. et al. Akkermansia muciniphila Adheres to Enterocytes and Strengthens the Integrity of the Epithelial Cell Layer. Appl. Environ. Microbiol. 81 (11), 3655–3662. https://doi.org/10.1128/AEM.04050-14 (2015).

    Google Scholar 

  22. Ouyang, J. et al. The bacterium Akkermansia muciniphila: A sentinel for gut permeability and its relevance to HIV-related inflammation. Front. Immunol. 11-2020. https://doi.org/10.3389/fimmu.2020.00645 (2020).

    Google Scholar 

  23. Routy, B. et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359 (6371), 91–97. https://doi.org/10.1126/science.aan3706 (2018).

    Google Scholar 

  24. Baruch, E. N. et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science 371 (6529), 602–609. https://doi.org/10.1126/science.abb5920 (2021).

    Google Scholar 

  25. Davar, D. et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science 371 (6529), 595–602. https://doi.org/10.1126/science.abf3363 (2021).

    Google Scholar 

  26. Gu, C. et al. Therapeutic potential of fecal microbiota transplantation in colorectal cancer based on gut microbiota regulation: From pathogenesis to efficacy. Therap Adv Gastroenterol https://doi.org/10.1177/17562848251327167 (2025).

    Google Scholar 

  27. Jiang, S. et al. An emerging strategy: probiotics enhance the effectiveness of tumor immunotherapy via mediating the gut microbiome. Gut Microbes. 16 (1), 2341717. https://doi.org/10.1080/19490976.2024.2341717 (2024).

    Google Scholar 

  28. Chandrasekaran, P., Weiskirchen, S. & Weiskirchen, R. Effects of Probiotics on Gut Microbiota: An Overview. Int. J. Mol. Sci. 25 (11), 6022 (2024). https://www.mdpi.com/1422-0067/25/11/6022

    Google Scholar 

  29. Rowaiye, A. et al. Gut microbiota alteration - Cancer relationships and synbiotic roles in cancer therapies. Microbe 4, 100096. https://doi.org/10.1016/j.microb.2024.100096 (2024).

    Google Scholar 

  30. Scott, A. J., Merrifield, C. A., Younes, J. A. & Pekelharing, E. P. Pre-, pro- and synbiotics in cancer prevention and treatment-a review of basic and clinical research. Ecancermedicalscience 12, 869. https://doi.org/10.3332/ecancer.2018.869 (2018).

    Google Scholar 

  31. Singh, N. K. et al. Synbiotics as Supplemental Therapy for the Alleviation of Chemotherapy-Associated Symptoms in Patients with Solid Tumours. Nutrients 15 (7), 1759 (2023). https://www.mdpi.com/2072-6643/15/7/1759

    Google Scholar 

  32. Huang, C. H., Cheng, J. Y., Deng, M. C., Chou, C. H. & Jan, T. R. Prebiotic effect of diosgenin, an immunoactive steroidal sapogenin of the Chinese yam. Food Chem. 132 (1), 428–432. https://doi.org/10.1016/j.foodchem.2011.11.016 (2012).

    Google Scholar 

  33. Dong, M. et al. Diosgenin promotes antitumor immunity and PD-1 antibody efficacy against melanoma by regulating intestinal microbiota. Cell. Death Dis. 9 (10), 1039. https://doi.org/10.1038/s41419-018-1099-3 (2018).

    Google Scholar 

  34. Zhang, J., Ma, X., Du, W., Mu, G. & Wu, X. Immune restoration mechanism analysis of Akkermansia PROBIO in mice treated with cyclophosphamide through Re-balancing microbiota composition. Food Bioscience. 68, 106450. https://doi.org/10.1016/j.fbio.2025.106450 (2025).

    Google Scholar 

  35. Derosa, L. & Zitvogel, L. A probiotic supplement boosts response to cancer immunotherapy. Nat. Med. 28 (4), 633–634. https://doi.org/10.1038/s41591-022-01723-4 (2022).

    Google Scholar 

  36. Gao, G. et al. Lacticaseibacillus rhamnosus Probio-M9 enhanced the antitumor response to anti-PD-1 therapy by modulating intestinal metabolites. EBioMedicine 91, 104533. https://doi.org/10.1016/j.ebiom.2023.104533 (2023).

    Google Scholar 

  37. Bhatt, A., Haslam, A. & Prasad, V. The effect of gastrointestinal microbiome supplementation on immune checkpoint inhibitor immunotherapy: a systematic review. J. Cancer Res. Clin. Oncol. 149 (10), 7355–7362. https://doi.org/10.1007/s00432-023-04656-8 (2023).

    Google Scholar 

  38. Zhao, S. et al. Assessing the impact of probiotics on immunotherapy effectiveness and antibiotic-mediated resistance in cancer: A systematic review and meta-analysis. Front. Immunol. 16, 2025. https://doi.org/10.3389/fimmu.2025.1538969 (2025).

    Google Scholar 

  39. Page, M. J. et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 372, n160. https://doi.org/10.1136/bmj.n160 (2021).

    Google Scholar 

  40. Higgins, J. P. T. et al. (eds) C,. Cochrane Handbook for Systematic Reviews of Interventions. version 5.2.0 (updated June (2017). https://training.cochrane.org/handbook: Cochrane; 2017.

  41. Slim, K. et al. Methodological index for non-randomized studies (minors): Development and validation of a new instrument. ANZ J. Surg. 73(9), 712–6. https://doi.org/10.1046/j.1445-2197.2003.02748.x (2003).

    Google Scholar 

  42. Barker, T. H. et al. Conducting proportional meta-analysis in different types of systematic reviews: A guide for synthesisers of evidence. BMC Med. Res. Methodol. 21(1), 189. https://doi.org/10.1186/s12874-021-01381-z (2021).

    Google Scholar 

  43. Jackson, D., Bowden, J. & Baker, R. How does the DerSimonian and Laird procedure for random effects meta-analysis compare with its more efficient but harder to compute counterparts?. J. Stat. Plan. Inference 140(4), 961–70. https://doi.org/10.1016/j.jspi.2009.09.017 (2010).

    Google Scholar 

  44. Balduzzi, S., Rücker, G. & Schwarzer, G. How to perform a meta-analysis with R: A practical tutorial. Evid. Based Ment. Health. 22(4), 153–60. https://doi.org/10.1136/ebmental-2019-300117 (2019).

    Google Scholar 

  45. Al Amer, F. M. & Lin, L. Empirical assessment of prediction intervals in Cochrane meta-analyses. Eur. J. Clin. Invest. 51(7), e13524. https://doi.org/10.1111/eci.13524 (2021).

    Google Scholar 

  46. Baruch, E. N. et al. Preliminary results from a microbiome-based phase i clinical trial - Fecal microbiota transplantation in metastatic melanoma patients who failed immunotherapy (NCT03353402). Pigment Cell. Melanoma Res. 32 (1), 97–98. https://doi.org/10.1111/pcmr.12738 (2019).

    Google Scholar 

  47. Baruch, E. N. et al. The gut microbiome enhances anti-PD-1 efficacy in a tumor-agnostic manner: results from a phase II trial of fecal microbiota transplantation and anti-PD-1 re-induction in MSI-H refractory cancers. J. Immunother. Cancer. 12, A1422. https://doi.org/10.1136/jitc-2024-SITC2024.1266 (2024).

    Google Scholar 

  48. Baruch, E. N. et al. Fecal microbiota transplantation (FMT) and re-induction of anti-PD-1 therapy in refractory metastatic melanoma patients - Preliminary results from a phase I clinical trial (NCT03353402). Cancer Res. 79 (13). https://doi.org/10.1158/1538-7445.SABCS18-CT042 (2019).

  49. Bergerot, P. et al. Pilot study to evaluate the biologic effect of the probiotic CBM588 in combination with nivolumab/ ipilimumab for patients with mRCC. Kidney Cancer. 4, S45. https://doi.org/10.3233/KCA-200001 (2020).

    Google Scholar 

  50. Ciccarese, C. et al. Fecal microbiota transplantation (FMT) versus placebo in patients receiving pembrolizumab plus axitinib for metastatic renal cell carcinoma: Preliminary results of the randomized phase II TACITO trial. Ann. Oncol. https://doi.org/10.1016/j.annonc.2024.08.2320 (2024).

    Google Scholar 

  51. Dizman, N. et al. Randomized prospective trial assessing Bifidobacteriumcontaining probiotic supplementation in metastatic renal cell carcinoma (mRCC) patients receiving vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs). J. Clin. Oncol. https://doi.org/10.1200/JCO.2020.38.15_suppl.5078 (2020).

    Google Scholar 

  52. Duttagupta, S. et al. Phase II trial of fecal microbiota transplantation in combination with ipilimumab and nivolumab in patients with advanced cutaneous melanoma (FMT-LUMINate trial). Cancer Res. 84 (7). https://doi.org/10.1158/1538-7445.AM2024-CT258 (2024).

  53. Elkrief, A. et al. Phase II trial of fecal microbiota transplantation (FMT) plus immune checkpoint inhibition (ICI) in advanced non-small cell lung cancer and cutaneous melanoma (FMT-LUMINate). Ann. Oncol. https://doi.org/10.1016/j.annonc.2024.08.1126 (2024).

    Google Scholar 

  54. Espinoza, I. R. G. et al. Effect of probiotics on quality of life for patients with cancer undergoing immunotherapy. J. Clin. Oncol. https://doi.org/10.1200/JCO.2024.42.16_suppl.e24148 (2024).

    Google Scholar 

  55. Fernandes, R. et al. Preventing adverse events in patients with renal cell carcinoma treated with doublet immunotherapy using fecal microbiota transplantation (FMT): Initial results from perform a phase I study. J. Clin. Oncol. https://doi.org/10.1200/JCO.2022.40.16_suppl.4553 (2022).

    Google Scholar 

  56. Galizia, D. et al. 863P Microbiota and cytokines profile in patients (pts) affected by recurrent metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs) +/- chemotherapy (CT) and prebiotic inulin in the PRINCESS study. Ann. Oncol. 34, S560. https://doi.org/10.1016/j.annonc.2023.09.2009 (2023).

    Google Scholar 

  57. Huang, M. J. et al. Fecal Microbiota Transplantation Plus Rechallenging Immunotherapy in Patients with Advanced Non Small Cell Lung Cancer: An Exploratory Study. pp. S262–S3. (2024).

  58. Kim, Y. et al. Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor. Cell Host Microbe 32(8), 1380–93.e9. https://doi.org/10.1016/j.chom.2024.06.010 (2024).

    Google Scholar 

  59. Lenehan, J. G. et al. Combining Fecal Microbiota Transplantation with Immunotherapy in Treatment-Naive Patients with Advanced Melanoma. Pigment Cell. Melanoma Res. 35 (1), 139–140. https://doi.org/10.1111/pcmr.13018 (2022).

    Google Scholar 

  60. Meza, L. A. et al. Intestinal microbiome associated with development of grade 3/4 adverse in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab (N/I) and probiotic support: Results from a phase Ib study. J. Clin. Oncol. https://doi.org/10.1200/JCO.2022.40.6_suppl.374 (2022).

    Google Scholar 

  61. Morita, A. et al. Impacts of probiotics on the efficacies of immune checkpoint inhibitors with or without chemotherapy for patients with advanced non-small-cell lung cancer. Int. J. Cancer. 154(9), 1607–15. https://doi.org/10.1002/ijc.34842 (2024).

    Google Scholar 

  62. Nakatsukasa, H. et al. Clinical impact of concomitant BIO-three use in advanced or recurrent non-small cell lung cancer treated with immune-checkpoint inhibitor. Int. J. Clin. Oncol. 29(12), 1840–9. https://doi.org/10.1007/s10147-024-02622-z (2024).

    Google Scholar 

  63. Park, S. R. et al. Fecal microbiota transplantation combined with anti-PD-1 inhibitor for unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor. J. Clin. Oncol. 41(16), 105. https://doi.org/10.1200/jco.2023.41.16_suppl.105 (2023).

    Google Scholar 

  64. Pomej, K. et al. Fecal microbiota transplant combined with atezolizumab plus bevacizumab in patients with hepatocellular carcinoma who progressed on atezolizumab plus bevacizumab - interim analysis of the FAB-HCC phase II pilot study. Z. Gastroenterol. 62 (5), e479–e80. https://doi.org/10.1055/s-0044-1786886 (2024).

    Google Scholar 

  65. Routy, B. et al. Microbiome modification with fecal microbiota transplant from healthy donors before anti-PD1 therapy reduces primary resistance to immunotherapy in advanced and metastatic melanoma patients. J. Immunother. Cancer. 10, A645. https://doi.org/10.1136/jitc-2022-SITC2022.0614 (2022).

    Google Scholar 

  66. Routy, B. et al. Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: A phase I trial. Nat. Med. 29(8), 2121–32. https://doi.org/10.1038/s41591-023-02453-x (2023).

    Google Scholar 

  67. Spencer, C. N. et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science 374(6575), 1632–40. https://doi.org/10.1126/science.aaz7015 (2021).

    Google Scholar 

  68. Spreafico, A. et al. First-in-class microbial ecosystem therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial). Ann. Oncol. 34(6), 520–30. https://doi.org/10.1016/j.annonc.2023.02.011 (2023).

    Google Scholar 

  69. Tomita, Y. et al. Association of probiotic Clostridium butyricum therapy with survival and response to immune checkpoint blockade in patients with lung cancer. Cancer Immunol. Res. 8(10), 1236–42. https://doi.org/10.1158/2326-6066.CIR-20-0051 (2020).

    Google Scholar 

  70. Tong, L. et al. Evaluating Oral Probiotic Supplements as Complementary Treatment in Advanced Lung Cancer Patients Receiving ICIs: A Prospective Real-World Study. Cancer Control https://doi.org/10.1177/10732748241253959 (2024).

    Google Scholar 

  71. Ullern, A. et al. MITRIC: Microbiota transplant to cancer patients progressing on immunotherapy using feces from clinical responders. J. Immunother. Cancer 12, A767. https://doi.org/10.1136/jitc-2024-SITC2024.0669 (2024).

    Google Scholar 

  72. Wang, X. et al. Effect of probiotics combined with immune checkpoint suppressors and chemotherapeutic agents on digestive system function, intestinal immunity and prognosis in patients with metastatic colorectal carcinoma: A quasi-experimental study. BMC Gastroenterol. https://doi.org/10.1186/s12876-025-03604-9 (2025).

    Google Scholar 

  73. Wang, Y. et al. Concomitant medications alter clinical outcomes in patients with advanced digestive tract cancer receiving PD-1 checkpoint inhibitors combined with antiangiogenetic agents. J. Gastrointest. Cancer 55(3), 1388–400. https://doi.org/10.1007/s12029-024-01095-7 (2024).

    Google Scholar 

  74. Xue, Y. et al. Fecal microbiota transplantation combined with anti-PD-(L)1 inhibitors as first-line maintenance therapy for advanced gastric and non small cell lung cancer. J. Clin. Oncol. https://doi.org/10.1200/JCO.2024.42.16_suppl.2646 (2024).

    Google Scholar 

  75. Zhang, Y. et al. Fecal microbiota transplantation promotes immunotherapy sensitivity in refractory gastrointestinal cancer patients: open label, single-arm, single center, phase 1 study. (2024).

  76. Zhao, W. & Chen, Y. Fecal microbiota transplantation in combination with fruquintinib and tislelizumab in refractory microsatellite stable metastatic colorectal cancer: A single center phase II trial. Immuno-Oncology Technol. 16 https://doi.org/10.1016/j.iotech.2022.100214 (2022).

  77. Zhao, W. et al. Updated outcomes and exploratory analysis of RENMIN-215: Tislelizumab plus fruquintinib and fecal microbiota transplantation in refractory microsatellite stable metastatic colorectal cancer. Am. J. Cancer Res. 14(11), 5351–64. https://doi.org/10.62347/XKUJ3012 (2024).

    Google Scholar 

  78. Zhao, W. et al. Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: An open-label, single-arm, phase II trial (RENMIN-215). eClinicalMedicine https://doi.org/10.1016/j.eclinm.2023.102315 (2023).

    Google Scholar 

  79. Zhu, W. et al. Safety and preliminary efficacy of different doses of fecal microbiota capsule transplantation combined with anti-PD-1 inhibitor for patients with advanced malignant solid tumors. J. Clin. Oncol. https://doi.org/10.1200/JCO.2024.42.16_suppl.e14622 (2024).

    Google Scholar 

  80. Dizman, N. et al. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: A randomized phase 1 trial. Nat. Med. 28(4), 704–12. https://doi.org/10.1038/s41591-022-01694-6 (2022).

    Google Scholar 

  81. Zhang, Y. et al. Fecal microbiota transplantation promotes immunotherapy sensitivity in refractory gastrointestinal cancer patients: open label, single-arm, single center, phase 1 study. medRxiv https://doi.org/10.1101/2024.08.21.24312340 (2024).

    Google Scholar 

  82. Huang, M. J. et al. P2.11A.23 Fecal microbiota transplantation plus rechallenging immunotherapy in patients with advanced non small cell lung cancer: An exploratory study. J. Thorac. Oncol. 19(10), S262–S3. https://doi.org/10.1016/j.jtho.2024.09.472 (2024).

    Google Scholar 

  83. Wang, X. et al. Effect of probiotics combined with immune checkpoint suppressors and chemotherapeutic agents on digestive system function, intestinal immunity and prognosis in patients with metastatic colorectal carcinoma: A quasi-experimental study. BMC Gastroenterol. 25(1), 38. https://doi.org/10.1186/s12876-025-03604-9 (2025).

    Google Scholar 

  84. Kim, S., Kim, A., Shin, J.-Y. & Seo, J.-S. The tumor immune microenvironmental analysis of 2,033 transcriptomes across 7 cancer types. Sci. Rep. 10(1), 9536. https://doi.org/10.1038/s41598-020-66449-0 (2020).

    Google Scholar 

  85. Liu, Y., Wang, J. & Wu, C. Modulation of gut microbiota and immune system by probiotics, pre-biotics, and post-biotics. Front. Nutr. 8, 2021. https://doi.org/10.3389/fnut.2021.634897 (2022).

    Google Scholar 

  86. Chen, S. et al. Response efficacy of PD-1 and PD-L1 inhibitors in clinical trials: A systematic review and meta-analysis. Front. Oncol. 11, 562315. https://doi.org/10.3389/fonc.2021.562315 (2021).

    Google Scholar 

  87. Mangla, A. et al. Neoadjuvant Dual Checkpoint Inhibitors vs Anti-PD1 Therapy in High-Risk Resectable Melanoma: A Pooled Analysis. JAMA Oncol. 10 (5), 612–620. https://doi.org/10.1001/jamaoncol.2023.7333 (2024).

    Google Scholar 

  88. Mc Neil, V. & Lee, S. W. Advancing Cancer Treatment: A Review of Immune Checkpoint Inhibitors and Combination Strategies. Cancers 17 (9), 1408 (2025). https://www.mdpi.com/2072-6694/17/9/1408

    Google Scholar 

  89. Devaraji, M. & Varghese Cheriyan, B. Immune-based cancer therapies: mechanistic insights, clinical progress, and future directions. J. Egypt. Natl Cancer Inst. 37 (1), 62. https://doi.org/10.1186/s43046-025-00319-6 (2025).

    Google Scholar 

  90. Alsaafeen, B. H., Ali, B. R. & Elkord, E. Resistance mechanisms to immune checkpoint inhibitors: updated insights. Mol. Cancer. 24 (1), 20. https://doi.org/10.1186/s12943-024-02212-7 (2025).

    Google Scholar 

  91. Baruch, E. N., Gaglani, T. & Wargo, J. A. Fecal microbiota transplantation as a mean of overcoming immunotherapy-resistant cancers - hype or hope? Ther. Adv. Med. Oncol. 13, 17588359211045853. https://doi.org/10.1177/17588359211045853 (2021).

    Google Scholar 

  92. Yang, Y. et al. Fecal microbiota transplantation: no longer cinderella in tumour immunotherapy. eBioMedicine 100, 104967. https://doi.org/10.1016/j.ebiom.2024.104967 (2024).

    Google Scholar 

  93. De Palma, M. & Hanahan, D. The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities. Mol. Oncol. 6 (2), 111–127. https://doi.org/10.1016/j.molonc.2012.01.011 (2012).

    Google Scholar 

  94. Zhang, L. et al. The correlation between probiotic use and outcomes of cancer patients treated with immune checkpoint inhibitors. Front. Pharmacol. 13, 937874. https://doi.org/10.3389/fphar.2022.937874 (2022).

    Google Scholar 

  95. Batista, V. L. et al. Probiotics, prebiotics, synbiotics, and paraprobiotics as a therapeutic alternative for intestinal mucositis. Front. Microbiol. 11, 2020. https://doi.org/10.3389/fmicb.2020.544490 (2020).

    Google Scholar 

  96. Spencer, C. N. et al. Abstract 2838: The gut microbiome (GM) and immunotherapy response are influenced by host lifestyle factors. Cancer Res. 79 (13_Supplement), 2838. https://doi.org/10.1158/1538-7445.Am2019-2838 (2019).

    Google Scholar 

  97. Ajab, S. M. et al. Microbiota composition effect on immunotherapy outcomes in colorectal cancer patients: A systematic review. PLoS. One 19(7), e0307639. https://doi.org/10.1371/journal.pone.0307639 (2024).

    Google Scholar 

  98. Kang, X., Lau, H. C. & Yu, J. Modulating gut microbiome in cancer immunotherapy: Harnessing microbes to enhance treatment efficacy. Cell Rep. Med. 5(4), 101478. https://doi.org/10.1016/j.xcrm.2024.101478 (2024).

    Google Scholar 

  99. Lei, W., Zhou, K., Lei, Y., Li, Q. & Zhu, H. Gut microbiota shapes cancer immunotherapy responses. Npj. Biofilms Microbiomes 11(1), 143. https://doi.org/10.1038/s41522-025-00786-8 (2025).

    Google Scholar 

  100. Sun, J. et al. Gut microbiota as a new target for anticancer therapy: From mechanism to means of regulation. Npj. Biofilms Microbiomes 11(1), 43. https://doi.org/10.1038/s41522-025-00678-x (2025).

    Google Scholar 

  101. Xu, Q. et al. The oral-gut microbiota axis: A link in cardiometabolic diseases. Npj. Biofilms Microbiomes 11(1), 11. https://doi.org/10.1038/s41522-025-00646-5 (2025).

    Google Scholar 

  102. Blaut, M. & Clavel, T. Metabolic diversity of the intestinal microbiota: Implications for health and disease1,. J. Nutr. 137(3), 751S–5S. https://doi.org/10.1093/jn/137.3.751S (2007).

    Google Scholar 

  103. Jin, Y., Jie, Z. & Fan, X. Gut microbes and immunotherapy for non-small cell lung cancer: A systematic review. Front. Oncol. 15, 2025. https://doi.org/10.3389/fonc.2025.1518474 (2025).

    Google Scholar 

  104. Lim, M. Y., Hong, S. & Nam, Y.-D. Understanding the role of the gut microbiome in solid tumor responses to immune checkpoint inhibitors for personalized therapeutic strategies: A review. Front. Immunol. 15, 2024. https://doi.org/10.3389/fimmu.2024.1512683 (2025).

    Google Scholar 

  105. Jayathilaka, B., Mian, F., Franchini, F., Au-Yeung, G. & Ijzerman, M. Cancer and treatment specific incidence rates of immune-related adverse events induced by immune checkpoint inhibitors: A systematic review. Br. J. Cancer. 132(1), 51–57. https://doi.org/10.1038/s41416-024-02887-1 (2025).

    Google Scholar 

Download references

Funding

This project is funded by the National Research Council of Thailand (NRCT): the High-Potential Research Team Grant Program (N42A680423) and the Rachadapisek Sompote Matching Fund (RA-MF-01/69). The academic endeavors of the Thailand Hub of Talents in Cancer Immunotherapy (TTCI) receive support from the National Research Council of Thailand. NH and MT were funded by the Second Century Fund (C2F), Chulalongkorn University. HL, VM, and ND were supported by the Graduate Scholarship Programme for ASEAN or Non-ASEAN Countries, Chulalongkorn University. The funder did not influence the results/outcomes of the study despite author affiliations with the funde

Author information

Authors and Affiliations

  1. Center of Excellence in Immunology and Immune-Mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    May Soe Thu, Ho Bao Chau Le, Nguyen Phuc Duc & Nattiya Hirankarn

  2. Graduate Program in Medical Sciences, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Ho Bao Chau Le & Nguyen Phuc Duc

  3. Graduate Program in Clinical Sciences, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Van Hieu Mai

  4. Department of Molecular Biology and Genetics, Faculty of Medicine, University of Health Sciences, Vietnam National University Ho Chi Minh City, Ho Chi Minh City, 700000, Vietnam

    Van Hieu Mai

  5. Master Program of Biological Sciences, School of Biosciences, University of Liverpool, Liverpool, L69 7ZX, UK

    Nina Walker

Authors
  1. May Soe Thu
    View author publications

    Search author on:PubMed Google Scholar

  2. Ho Bao Chau Le
    View author publications

    Search author on:PubMed Google Scholar

  3. Nguyen Phuc Duc
    View author publications

    Search author on:PubMed Google Scholar

  4. Van Hieu Mai
    View author publications

    Search author on:PubMed Google Scholar

  5. Nina Walker
    View author publications

    Search author on:PubMed Google Scholar

  6. Nattiya Hirankarn
    View author publications

    Search author on:PubMed Google Scholar

Contributions

MT and NH contributed to conceptualization, supervision, and critical revision of the manuscript. The MT took a role in project administration and introduced the required software and resources. MT, HL, VM, and ND contributed to the data curation, formal analysis, and methodology. All the authors contributed to the writing and editing of the manuscript. All the authors read and approved the final manuscript. NH is the guarantor of the review for the integrity of the work as a whole.

Corresponding author

Correspondence to Nattiya Hirankarn.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1 (download DOCX )

Supplementary Material 2 (download DOCX )

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Thu, M.S., Le, H.B.C., Duc, N.P. et al. Impact of microbiome-modulating strategies in cancer patients receiving immunotherapy (MSIT): A systematic review and meta-analysis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-44743-7

Download citation

  • Received: 17 November 2025

  • Accepted: 13 March 2026

  • Published: 17 March 2026

  • DOI: https://doi.org/10.1038/s41598-026-44743-7

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • Microbiome
  • Probiotics
  • Faecal microbiota transplantation
  • Immunotherapy
  • Immune checkpoint inhibitors
Download PDF

Advertisement

Explore content

  • Research articles
  • News & Comment
  • Collections
  • Subjects
  • Follow us on Facebook
  • Follow us on X
  • Sign up for alerts
  • RSS feed

About the journal

  • About Scientific Reports
  • Contact
  • Journal policies
  • Guide to referees
  • Calls for Papers
  • Editor's Choice
  • Journal highlights
  • Open Access Fees and Funding

Publish with us

  • For authors
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

Scientific Reports (Sci Rep)

ISSN 2045-2322 (online)

nature.com footer links

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer