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Fecal microbiota transplantation in capsules for the treatment of steroid refractory and steroid dependent acute graft vs. host disease: a pilot study

Bone Marrow Transplantation volume 59, pages 409–416 (2024)Cite this article

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Abstract

Acute graft-versus-host disease (aGvHD) is a serious complication of allogeneic hematopoietic stem-cell transplantation with limited treatment options. The gut microbiome plays a critical role in aGvHD pathogenesis. Fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach to restore gut microbial diversity. In this prospective pilot study, 21 patients with steroid-resistant or steroid-dependent lower gastrointestinal aGvHD received FMT in capsule form. At 28 days after the first FMT, the overall response rate was 52.4%, with 23.8% complete and 28.6% partial responses. However, sustained responses were infrequent, with only one patient remaining aGvHD-free long-term. FMT was generally well-tolerated. Microbiome analysis revealed dysbiosis in pre-FMT patient stool samples, with distinct microbial characteristics compared to donors. Following FMT, there was an increase in beneficial Clostridiales and a decrease in pathogenic Enterobacteriales. These findings highlight the potential of FMT as a treatment option for steroid-resistant aGvHD. Trial registration number NCT #03214289.

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Fig. 1: Patient trajectories following FMT.
Fig. 2: Response and overall survival following FMT.
Fig. 3: Microbiota characterization of pre-FMT patients’ samples.
Fig. 4: Microbiota dynamics as a response to FMT treatment.

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Data availability

Data are available upon request from the corresponding author and approval of data transfer from the IRB.

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Funding

Funding

RS was supported by Memorial Sloan Kettering Cancer Center Core grant (P30 CA008748) from the National Institutes of Health/National Cancer Institute and by an NIH-NCI K-award (K08CA282987). The study was supported by the Dahlia Greidinger Anti Cancer Fund, the Gassner Fund for Medical Research, and an institutional grant from the Chaim Sheba Medical Center.

Author information

Author notes

  1. These authors contributed equally: Ilan Youngster, Adi Eshel.

  2. These authors jointly supervised this work: Omry Koren, Roni Shouval, Arnon Nagler.

Authors and Affiliations

  1. Shamir Medical Center, Beer Yaacov, Israel

    Ilan Youngster

  2. Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Ilan Youngster, Mika Geva, Ivetta Danylesko, Shalev Fried, Ronit Yerushalmi, Noga Shem-Tov, Avichai Shimoni, Roni Shouval & Arnon Nagler

  3. Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel

    Adi Eshel & Omry Koren

  4. Hematology and Bone Marrow Transplantation Division, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

    Mika Geva, Ivetta Danylesko, Shalev Fried, Ronit Yerushalmi, Noga Shem-Tov, Avichai Shimoni, Roni Shouval & Arnon Nagler

  5. Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel

    Israel Henig & Tsila Zuckerman

  6. Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel

    Tsila Zuckerman & David Bomze

  7. Department of Medicine, Weill Cornell Medical College, New York, NY, USA

    Joshua A. Fein

  8. Division of Dermatology, Sourasky Medical Center, Tel Aviv, Israel

    David Bomze

  9. Adult BMT Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Roni Shouval

  10. Weill Cornell Medical College, New York, NY, USA

    Roni Shouval

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  1. Ilan Youngster
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Contributions

IY, RS, AN planned the study. AE, RS, DB, and RS analyzed the data. RS, ID, and TZ enrolled patients. IY manufactured the fecal microbiota transplant capsules. MG coded data into the database. RS wrote the manuscript. IY, OK, RS, and AN supervised the analysis and study. All authors edited and reviewed the manuscript.

Corresponding author

Correspondence to Roni Shouval.

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Youngster, I., Eshel, A., Geva, M. et al. Fecal microbiota transplantation in capsules for the treatment of steroid refractory and steroid dependent acute graft vs. host disease: a pilot study. Bone Marrow Transplant 59, 409–416 (2024). https://doi.org/10.1038/s41409-024-02198-2

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