Study Explores Fecal Microbiota Transplantation for Patients Healing After Stem Cell Transplantation

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A recent study published in Nature Communications highlights the potential of oral fecal microbiota transplantation (FMT) as a viable and safe approach to preventing graft-versus-host disease (GVHD) in patients undergoing stem cell transplants for blood cancers. This work represents a significant step forward in exploring how the gut microbiome can support recovery and improve outcomes for these patients.

The research, led by clinicians at Fred Hutch Cancer Center, is part of a phase 2 clinical trial and builds on previous findings about the microbiome’s role in recovery following stem cell transplantation.

“The gut microbiome is an organ in itself, and it is connected to the immune system,” explained Armin Rashidi, MD, PhD, the study’s lead author and a medical oncologist at Fred Hutch. “Since the process of stem cell transplantation damages the gut microbiome, we want to see if FMT will help restore microbial diversity and promote the beneficial bacterial species that support a healthy immune system.”

The trial included 20 patients with blood cancers or related blood disorders who underwent allogeneic stem cell transplantation. Following their transplants, these patients received oral FMT capsules, taken three times a day for seven days. The capsules contained a purified mix of microbes derived from stool samples provided by three healthy donors. These capsules were produced by the University of Minnesota Microbiota Therapeutics Program under FDA-approved protocols.

“Although the capsules were originally developed for the treatment of recurrent Clostridioides difficile infection, they are now being investigated for a multitude of different indications,” noted Dr. Alexander Khoruts, a coauthor of the study and a gastroenterologist at the University of Minnesota Medical School. “Unlike treatment of C. difficile, most indications require optimized formulations of gut microbes. The Fred Hutch trial illustrates this next phase in the development of donor-derived microbial therapeutics.”

Key Findings

  1. Donor Microbial Differences: The effectiveness of the FMT varied significantly depending on the donor. One donor in particular, referred to as Donor 3, achieved a microbiota engraftment rate of 67 percent. This means that 67 percent of the microbes in patients after FMT came from this donor. This donor’s stool was notably rich in Bifidobacterium adolescentis, a microbe associated with gut health.
  2. Impact of Microbiota Diversity: Patients with lower microbial diversity before undergoing FMT had better donor microbiota engraftment. This finding aligns with previous research suggesting that a less diverse gut environment may offer transplanted microbes a greater opportunity to establish themselves.
  3. Safety of FMT: The treatment was deemed safe, even for patients with compromised immune systems. The transfer of live microbes from healthy donors did not lead to infections, and some microbial species reached a 100 percent engraftment rate. These beneficial microbes are known to support gut health and protect against GVHD. “Our study shows that when done following proper regulation in a clinical trial, FMT is safe,” Dr. Rashidi said. “There had been concerns of giving live microbes to people who are immunocompromised, but this study and our 2023 study before it show no major toxicity, which should be reassuring to patients and their families.”

According to the authors, this study served as a preparatory phase to identify the most effective donor for a larger randomized trial. The ongoing trial, led by Dr. Rashidi, aims to evaluate whether FMT improves outcomes for patients undergoing allogeneic stem cell transplantation. With a target of enrolling 126 patients, this phase will compare results between those receiving FMT from the top-performing donor and those receiving a placebo.

The researchers said they hope their findings pave the way for significant improvements in patient outcomes, including reduced acute GVHD, fewer infections, shorter hospital stays, and improved quality of life.

“The hope of using FMT with people receiving stem cell transplants is that FMT will help prevent acute GVHD without adding more immunosuppression, improve quality of life, and decrease mortality after transplant,” Dr. Rashidi said.

The study also explained that FMT is being explored for other conditions, including autism, colitis, inflammatory bowel disease, and irritable bowel syndrome, reflecting growing interest in its therapeutic potential.