Oral fecal microbiota transplantation may be a feasible and safe option to prevent graft-vs-host disease in patients with hematologic malignancies undergoing allogeneic stem cell transplant (ASCT), according to a recent report published by Reddi et al in Nature Communications. The findings built on previous research of the role of the gut microbiome in helping patients recover following ASCT.
Background
In 2023, the U.S. Food and Drug Administration (FDA) approved oral fecal microbiota transplantation to treat infectious types of diarrheas.
“The gut microbiome is an organ in itself, and it is connected to the immune system,” explained senior study author Armin Rashidi, MD, PhD, a medical oncologist at Fred Hutch Cancer Center. “Since the process of stem cell transplantation damages the gut microbiome, we want to see if [fecal microbiota transplantation] will help restore microbial diversity and promote the beneficial bacterial species that support a healthy immune system,” he continued.
Study Methods and Results
In the study—part of a phase II clinical trial—researchers assigned 20 patients who underwent ASCT for various hematologic malignancies to receive fecal microbiota transplantation via oral capsules three times per day for 7 days. The capsules contained a purified community of microbes derived from the stool samples of three healthy donors. The capsules were manufactured in accordance with FDA-approved investigational protocols and strict pharmaceutical standards.
The trial analyzed three different fecal microbiota transplantation donors and found notable differences in how well each one established itself in the recipient. The third donor emerged as the most effective, achieving a 67% microbiota engraftment rate—indicating that among all the microbes following fecal microbiota transplantation whose origin could be determined with certainty, 67% came from the donor and the remaining 33% were from the patient. This donor was characterized by high levels of the beneficial bacterium Bifidobacterium adolescentis.
Consistent with prior research, the researchers also found that lower pre–fecal microbiota transplantation microbiota diversity in the patients was associated with greater donor microbiota engraftment. The results suggested that less diverse pre–fecal microbiota transplantation gut environments may make it easier for transplanted microbes to establish themselves.
Fecal microbiota transplantation 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 beneficial microbes from a healthy donor. Engraftment reached 100% for some microbial species known to support overall gut health and protect against graft-vs-host disease.
“Our study shows that when done following proper regulation in a clinical trial, [fecal microbiota transplantation] is safe,” Dr. Rashidi noted. “There had been concerns of giving live microbes to [patients] 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,” he revealed.
Conclusions
“Although the capsules were originally developed for treatment of recurrent Clostridioides difficile infection, they are now being investigated for a multitude of different indications,” highlighted co–study author Alexander Khoruts, MD, a gastroenterologist at the University of Minnesota Medical School. “Unlike [the] 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,” he emphasized.
The researchers reported on the clinical trial’s 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 trial will explore whether fecal microbiota transplantation improves health outcomes—such as less acute graft-vs-host disease, fewer hospitalizations, fewer infections, better quality of life, and longer survival—in patients undergoing ASCT. The trial will include 126 patients randomly assigned to receive either fecal microbiota transplantation from the most effective donor identified from the new study or placebo.
“The hope of using [fecal microbiota transplantation] with [patients] receiving stem cell transplants is that [this type of treatment] will help prevent acute [graft-vs-host disease] without adding more immunosuppression, improve quality of life, and decrease mortality after transplant,” Dr. Rashidi underscored. “Our findings … give another evidence-based example of how the gut microbiome can be used to improve human health,” he concluded.
Disclosure: The research in this 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. For full disclosures of the study authors, visit nature.com.
