Fecal Microbiota Transplantation Shows Promise in Preventing Graft-versus-Host Disease After Stem Cell Transplants
核心洞察
A phase 2 clinical trial demonstrates that oral fecal microbiota transplantation (搜索) (FMT) is a safe and feasible approach to prevent graft-versus-host disease (搜索) (GVHD) in stem cell transplant recipients.
The study identifies donor-specific effects, with FMT from Donor 3 showing the highest microbiota engraftment rate and a favorable safety profile.
Lower pre-FMT microbiota diversity in patients was associated with better donor microbiota engraftment, suggesting a more receptive gut environment for transplanted microbes.
A new study from Fred Hutch Cancer Center (搜索), published in Nature Communications, reveals that fecal microbiota transplantation (搜索) (FMT) could be a safe and effective method for preventing acute graft-versus-host disease (搜索) (aGVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (搜索) (alloHCT (搜索)). The phase 2 clinical trial highlights the importance of donor selection and the potential of FMT to restore gut microbiome diversity, which is often disrupted by stem cell transplants.
Donor-Specific Effects on Microbiota Engraftment
The study involved 20 patients who received FMT via oral capsules following alloHCT (搜索) for various blood disorders. The capsules contained purified microbes from three healthy donors. Researchers found significant differences in engraftment rates depending on the donor. Donor 3 showed the highest engraftment rate at 67%, characterized by high levels of Bifidobacterium adolescentis (搜索), a microbe known for its beneficial effects. In contrast, FMT from Donor 1 was associated with worse outcomes, including severe aGVHD in three patients.
Impact on Microbiota Diversity and Composition
The trial demonstrated that FMT effectively restored microbiota diversity, shifting the recipient's gut microbiome composition closer to that of the donor. This shift was more pronounced with Donor 3, suggesting that specific microbial species may play a protective role against GVHD. Pre-FMT microbiota diversity was negatively associated with engraftment, indicating that patients with less diverse gut environments before FMT had better engraftment rates.
Safety and Feasibility of FMT
The study confirmed the safety of FMT in immunocompromised patients, with no major adverse events reported. Transient grade 1-2 gastrointestinal symptoms were the most common side effects. According to Armin Rashidi, MD, PhD, lead author and medical oncologist at Fred Hutch, this trial and a previous 2023 study show no major toxicity, reassuring patients and their families about the safety of FMT.
Implications for GVHD Prevention
Acute GVHD (搜索) remains a significant cause of morbidity and mortality after alloHCT (搜索), affecting up to half of patients despite standard immunosuppressive prophylaxis. Disruptions in the intestinal microbiota during the early peri-engraftment period have been linked to increased incidence and severity of aGVHD. The study's findings suggest that FMT can mitigate this risk by restoring a more favorable gut environment.
Ongoing Randomized Clinical Trial
The Nature Communications paper reports on the clinical trial's "run-in" period, a preparation phase to find the best of three stool donors to be used for the larger randomized trial which is now actively enrolling patients. A larger, randomized phase 2 clinical trial is underway, led by Rashidi, to assess whether FMT improves health outcomes for patients undergoing alloHCT (搜索). The trial will include 126 patients randomly assigned to either FMT from the "winning" donor or a placebo group. The primary endpoint is grade III-IV aGVHD at 6 months post-HCT. Secondary endpoints include grade II-IV aGVHD, non-relapse mortality, and Clostridioides difficile (搜索) infection at 6 months post-HCT, and chronic GVHD at 1 year post-HCT.
Future Directions
These findings underscore the potential of FMT as a therapeutic strategy to improve outcomes in stem cell transplantation (搜索). The ongoing randomized trial will provide further insights into the efficacy of FMT in preventing severe aGVHD and improving overall survival. The study highlights the importance of donor selection and the need for personalized approaches to microbiome restoration in alloHCT (搜索) recipients.