Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect
Abstract Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantat...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56375-y |
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| author | Swetha Reddi Liliia Senyshyn Maryam Ebadi Daniel Podlesny Samuel S. Minot Ted Gooley Amanda J. Kabage Geoffrey R. Hill Stephanie J. Lee Alexander Khoruts Armin Rashidi |
| author_facet | Swetha Reddi Liliia Senyshyn Maryam Ebadi Daniel Podlesny Samuel S. Minot Ted Gooley Amanda J. Kabage Geoffrey R. Hill Stephanie J. Lee Alexander Khoruts Armin Rashidi |
| author_sort | Swetha Reddi |
| collection | DOAJ |
| description | Abstract Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantation (FMT) early after alloHCT reduces the incidence of severe aGVHD. Here, we report the results from the single-arm run-in phase which identified the best of 3 stool donors for the randomized phase. The primary and key secondary endpoints were microbiota engraftment and severe aGVHD, respectively. Three cohorts of patients (20 total) received FMT, each from a different donor. FMT was safe and effective in restoring microbiota diversity and commensal species. Microbiota engraftment, determined from shotgun sequencing data, correlated with larger microbiota compositional shifts toward donor and better clinical outcomes. Donor 3 yielded a median engraftment rate of 66%, higher than donors 1 (P = 0.02) and 2 (P = 0.03) in multivariable analysis. Three patients developed severe aGVHD; all 3 had received FMT from donor 1. Donor 3 was selected as the sole donor for the randomized phase. Our findings suggest a clinically relevant donor effect and demonstrate feasibility of evidence-based donor selection. FMT is a holistic microbiota restoration approach that can be performed as a precision therapeutic. ClinicalTrials.gov identifier NCT06026371 |
| format | Article |
| id | doaj-art-aa241ecdde1946fcae3773d256733fc2 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-aa241ecdde1946fcae3773d256733fc22025-01-26T12:41:14ZengNature PortfolioNature Communications2041-17232025-01-0116111310.1038/s41467-025-56375-yFecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effectSwetha Reddi0Liliia Senyshyn1Maryam Ebadi2Daniel Podlesny3Samuel S. Minot4Ted Gooley5Amanda J. Kabage6Geoffrey R. Hill7Stephanie J. Lee8Alexander Khoruts9Armin Rashidi10Department of Internal Medicine, University of WashingtonClinical Research Division, Fred Hutchinson Cancer CenterDepartment of Radiation Oncology, University of WashingtonEuropean Molecular Biology Laboratory (EMBL)Data Core, Shared Resources, Fred Hutchinson Cancer CenterClinical Research Division, Fred Hutchinson Cancer CenterDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of MinnesotaTranslational Science and Therapeutics Division, Fred Hutchinson Cancer CenterClinical Research Division, Fred Hutchinson Cancer CenterDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of MinnesotaClinical Research Division, Fred Hutchinson Cancer CenterAbstract Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantation (FMT) early after alloHCT reduces the incidence of severe aGVHD. Here, we report the results from the single-arm run-in phase which identified the best of 3 stool donors for the randomized phase. The primary and key secondary endpoints were microbiota engraftment and severe aGVHD, respectively. Three cohorts of patients (20 total) received FMT, each from a different donor. FMT was safe and effective in restoring microbiota diversity and commensal species. Microbiota engraftment, determined from shotgun sequencing data, correlated with larger microbiota compositional shifts toward donor and better clinical outcomes. Donor 3 yielded a median engraftment rate of 66%, higher than donors 1 (P = 0.02) and 2 (P = 0.03) in multivariable analysis. Three patients developed severe aGVHD; all 3 had received FMT from donor 1. Donor 3 was selected as the sole donor for the randomized phase. Our findings suggest a clinically relevant donor effect and demonstrate feasibility of evidence-based donor selection. FMT is a holistic microbiota restoration approach that can be performed as a precision therapeutic. ClinicalTrials.gov identifier NCT06026371https://doi.org/10.1038/s41467-025-56375-y |
| spellingShingle | Swetha Reddi Liliia Senyshyn Maryam Ebadi Daniel Podlesny Samuel S. Minot Ted Gooley Amanda J. Kabage Geoffrey R. Hill Stephanie J. Lee Alexander Khoruts Armin Rashidi Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect Nature Communications |
| title | Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect |
| title_full | Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect |
| title_fullStr | Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect |
| title_full_unstemmed | Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect |
| title_short | Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect |
| title_sort | fecal microbiota transplantation to prevent acute graft versus host disease pre planned interim analysis of donor effect |
| url | https://doi.org/10.1038/s41467-025-56375-y |
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