Oral fecal transplantation could help prevent graft-versus-host disease in stem cell transplant patients

A new study shows that oral fecal microbiota transplantation (FMT) is a feasible and safe addition to preventing graft-versus-host disease in patients undergoing stem cell transplantation for blood cancers.

The study, published Jan. 25 in Nature Communications, is part of a phase 2 clinical trial led by clinicians at Fred Hutch Cancer Center. The study builds on earlier research of the role of the gut microbiome in helping patients recover after stem cell transplantation.

The gut microbiome is an organ in itself, and it is connected to the immune system. 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."

Armin Rashidi, MD, PhD, lead author, medical oncologist at Fred Hutch

The study included 20 patients who underwent allogeneic stem cell transplantations for various blood disorders including blood cancers. They then received FMT via oral capsules taken three times a day for seven days. The capsules contained a purified community of microbes derived from stool samples from three healthy donors.

The capsules were manufactured by the University of Minnesota Microbiota Therapeutics Program in accordance with the FDA-approved investigational protocols and strict pharmaceutical standards.

"Although the capsules were originally developed for treatment of recurrent Clostridioides difficile infection, they are now being investigated for a multitude of different indications," said Alexander Khoruts, MD, coauthor of the paper 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:

• Donor Differences Matter: The trial analyzed three different FMT donors and found notable differences in how well each one established itself in the recipient. Donor 3 emerged as the most effective, achieving a 67% microbiota engraftment rate. This means of all the microbes after FMT whose origin could be determined with certainty, 67% came from the donor and the remaining were from the patient. This "winning" donor was characterized by high levels of Bifidobacterium adolescentis, a beneficial microbe.
• Microbiota Diversity Influences Success: Consistent with prior research, the study found that lower pre-FMT microbiota diversity in patients was associated with better donor microbiota engraftment. This suggests that less diverse pre-FMT gut environments may make it easier for transplanted microbes to establish themselves.
• FMT is Safe: FMT was shown to be safe even in highly immunocompromised patients. The transfer of millions of live microbes to the patient did not cause any infections, likely because they were "healthy" microbes from a healthy donor. Engraftment reached 100% for some microbial species known to support overall gut health and protect against graft-versus-host disease.

"Our study shows that when done following proper regulation in a clinical trial, FMT is safe," 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."

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.

The randomized phase 2 clinical trial, led by Rashidi, will study whether FMT improves health outcomes for patients undergoing allogeneic stem cell transplantation, such as less acute GVHD, fewer hospitalizations, fewer infections, better quality of life and longer survival. The trial will include 126 patients randomly assigned to either FMT from the "winning" donor identified from the Nature Communications study or to a placebo group. The trial site is at Fred Hutch in Seattle.

"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," Rashidi said. "Our findings published in Nature Communications give another evidence-based example of how the gut microbiome can be used to improve human health."

Other clinical trials investigating FMT focus on treatments for autism, colitis, inflammatory bowel disease, and irritable bowel syndrome. In 2023, the U.S. FDA approved oral FMT to treat an infectious form of diarrhea.

The study was funded by the Leukemia & Lymphoma Society and the National Institutes of Health's award to the Fred Hutch/University of Washington/Seattle Children's Cancer Consortium. Manufacturing of the FMT product and placebo was partially supported by Achieving Cures Together, a nonprofit organization.

Note: To the extent any commercializable discoveries result from the aforementioned research, Fred Hutch and the scientists who contributed to the discoveries may stand to benefit from their future commercialization.

The clinical trials referenced above involve investigational products and/or therapies that have not been approved for commercial marketing by the U.S. Food and Drug Administration or any other regulatory authority. Results may vary and encouraging results from early-stage clinical trials may not be supported in later-stage clinical trials. No conclusions should be drawn from the information in this Tip Sheet or from the conference presentations about the safety, efficacy or likelihood of regulatory approval of these investigational products and/or therapies.

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