Fecal Transplants Show Safety, Potential to Enrich Gut in Small Trial
Repeated fecal transplants from healthy donors were safe and well-tolerated in a small group of people with relapsing-remitting multiple sclerosis (RRMS), a study reported.
Treatment also showed a potential to ease intestinal permeability in MS and enrich the presence of protective microbes in the gut.
Given that the trial was limited to nine patients, “further studies with longer follow-up and larger sample sizes are required to determine if [fecal transplant] is a suitable therapy for MS,” the researchers wrote.
The study, “Fecal microbiota transplantation is safe and tolerable in patients with multiple sclerosis: A pilot randomized controlled trial,” was published in the Multiple Sclerosis Journal – Experimental, Translational and Clinical.
The gut microbiome — a group of microbes living in the gastrointestinal tract — has received increasing attention for its potential role in the development and progression of neurological diseases, including multiple sclerosis (MS).
Evidence suggests the composition of the microbiome is altered in MS patients compared with healthy people. It has been proposed that these changes may alter gut permeability, allowing toxins to travel outside the gut and trigger autoimmune responses, exacerbating MS symptoms.
Studies also suggest that targeting the gut microbiome may be a therapeutic avenue for MS. Fecal transplants are one way to alter gut microbiota. The process involves the transfer of a small amount of stool from a healthy donor, allowing the presumably healthier microbe composition to grow in the recipient’s body.
A research team conducted a trial (NCT03183869) to investigate the potential benefits of fecal transplant in people with RRMS recruited at a neurology clinic in Ontario, Canada.
While initially aiming to enroll 40 patients, the study was affected by the sudden death of its principal investigator. Nine people, six women and three men, joined and were randomized to either an early (four patients) or late (five patients) treatment group. Patients’ mean age was 44, and their average disease duration was 14.6 years.
Those in the early group received a transplant once a month for up to six months, and then were monitored for another six months. Late intervention patients underwent the procedure in reverse, with six months of monitoring followed by up to six months of transplants.
In brief, stool samples were collected from either of two healthy donors and delivered via a rectal enema to patients with each transplant. Donors were pre-screened for microbes and biochemical characteristics of their blood, stool, and urine, and neither had a personal or family history of gastrointestinal, autoimmune, or other potentially confounding health conditions.
Six of the patients underwent six transplants, one had five transplants, and two others received two transplants.
Common reported adverse events included nausea, vomiting, and abdominal discomfort, but no serious adverse events. One event, determined to be related to the transplants, was an incident of hives, which resolved without treatment and did not recur.
Routine lab tests and clinical exams showed no significant safety findings.
Disability status, as determined by the Expanded Disability Status Scale, and MRI disease activity were unchanged with treatment.
The study’s primary goal was to assess changes in blood levels of cytokines, a family of inflammatory molecules, at various times after the first transplant. However, the trial’s unexpectedly small patient number prevented this analysis from being performed in full, and no significant differences were observed.
But results did show that elevated intestinal permeability was normalized after a full course of fecal transplants in two patients who had abnormal permeability prior to treatment.
Fecal transplants also led to changes in the gut microbiome. At the study’s start, MS patients had significantly higher levels of Bacteroides, Blautia faecis, and Bacteroides uniformis than the two donors, while donors tended to have a higher abundance of Prevotella 9 and Paraprevotella species.
Donors also generally showed a greater diversity of microbes in their stool than MS patients, which was unchanged with repeated transplants.
While patients did not acquire a more “donor-like” microbiome after transplants, differences in some particular microbes were observed. Microbes that were enriched after the transplants differed depending on which donor gave samples.
“MS-ameliorating functional alterations occurred,” the researchers wrote. They noted particular changes, which they suggested point to the possibility that fecal transplant may “exert clinically significant protective and preventative functional alterations to the MS microbiota.”
Overall, the findings “demonstrated that [fecal transplant] was a safe and tolerable intervention in this group of MS patients, with the potential to normalize intestinal permeability and produce beneficial alterations to the gut microbiota,” the researchers wrote.
Noting their trial was limited by size in its ability to observe changes in inflammation or disease disability, they added that “additional studies with larger more representative cohorts are required to determine the effect of [fecal transplant] in MS patients.”