Reddi Swetha, Senyshyn Liliia, Ebadi Maryam, Podlesny Daniel, Minot Samuel S, Gooley Ted, Kabage Amanda J, Hill Geoffrey R, Lee Stephanie J, Khoruts Alexander, Rashidi Armin
Department of Internal Medicine, University of Washington, Seattle, WA, USA.
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Nat Commun. 2025 Jan 25;16(1):1034. doi: 10.1038/s41467-025-56375-y.
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.
异基因造血细胞移植（alloHCT）后肠道微生物群的破坏与急性移植物抗宿主病（aGVHD）风险增加相关。我们设计了一项随机、双盲、安慰剂对照试验，以测试alloHCT后早期进行健康供体粪便微生物群移植（FMT）是否能降低严重aGVHD的发生率。在此，我们报告单臂导入期的结果，该阶段确定了随机阶段3名粪便供体中最佳的供体。主要和关键次要终点分别是微生物群植入和严重aGVHD。三组患者（共20例）接受了FMT，每组来自不同的供体。FMT在恢复微生物群多样性和共生菌种方面是安全有效的。根据鸟枪法测序数据确定的微生物群植入与微生物群组成向供体的更大变化以及更好的临床结果相关。在多变量分析中，供体3的中位植入率为66%，高于供体1（P = 0.02）和供体2（P = 0.03）。3例患者发生严重aGVHD；所有3例均接受了来自供体1的FMT。供体3被选为随机阶段的唯一供体。我们的研究结果表明存在临床相关的供体效应，并证明了基于证据的供体选择的可行性。FMT是一种整体微生物群恢复方法，可作为一种精准治疗方法实施。ClinicalTrials.gov标识符：NCT06026371。
