A new study from researchers at the Fred Hutch Cancer Center demonstrates that fecal microbiota transplantation (FMT) may be a valuable tool in improving the effectiveness of stem cell transplants, particularly by reducing the risk of Graft-versus-Host Disease (GVHD), a severe complication of the procedure.
The findings, published in Nature Communications, are part of a phase II clinical trial that 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,” said the study’s lead author Armin Rashidi, MD, PhD, 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.”
For this study, the researchers enrolled 20 patients who had received allogeneic stem cell transplants as treatment for a number of different blood cancers. Participants were given oral FMT capsules containing a purified mix of microbes from three different healthy stool donors. The treatment was administered three times daily for seven days, to attempt to restore the diversity of the gut microbiome, which is often disrupted by stem cell transplants.
The results revealed significant differences in the outcomes based on the donors chosen for the microbiota. The researchers found that FMT from one particular donor (Donor 3) had the most successful engraftment rate, with 67% of the microbes that originated from the donor found in the patient’s gut after the treatments. The investigators noted that this donor’s microbiota was characterized by high levels of Bifidobacterium adolescentis, a beneficial microbe linked to immune system support and anti-inflammatory effects.
FMT was also shown to be safe for these highly immunocompromised patients, with no major adverse events occurring during the trial.
“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 study’s findings have important implications for improving the effectiveness of stem cell transplants. Acute GVHD remains a leading cause of morbidity and mortality in patients undergoing allogeneic hematopoietic cell transplants (alloHCTs), with up to half of patients developing GVHD despite standard immunosuppressive treatments. While FMT is known to restore microbiome diversity, this study suggests it may also help mitigate the risk of GVHD by fostering a more favorable gut environment.
In the trial, patients who received FMT had a robust recovery in their gut microbiome diversity, particularly those treated with FMT from Donor 3. The composition of their microbiomes shifted closer to that of the donor’s, suggesting that certain beneficial species, such as Bifidobacterium adolescentis, may play a protective role against GVHD. Conversely, FMT from Donor 1 led to worse outcomes, including the occurrence of severe GVHD in three patients, which showed that not all healthy donors possess the right mix of microbial species in their microbiome to be suitable donors.
An interesting finding of the study was that patients with lower pre-treatment microbiota diversity responded better to FMT, suggesting that less diverse microbiomes may make it easier for donor microbes to establish themselves.
With the results of this study showing promise, the Fred Hutch team is now working on a larger trial that will enroll 126 patients. End goals of the new study are to assess whether FMT can reduce the incidence of severe GVHD, shorten hospital stays, decrease infections, and improve overall survival rates.
