Review Highlights Questions That Remain for Fecal Transplant in Parkinson’s

There currently is not enough data to support the use of fecal transplants as a treatment in Parkinson’s disease, a new review suggests.

Published in the Journal of Parkinson’s Disease, the review is titled “Faecal Transplantation, Pro- and Prebiotics in Parkinson’s Disease; Hope or Hype?”

The gut microbiome — the bacteria that live in the gut — have a documented impact on human health. Recent research has suggested that the gut microbiome in people with Parkinson’s disease (PD) is dysregulated and does not work properly. However, the exact changes that happen in PD are still unclear, with many studies finding conflicting results, and none able to demonstrate a cause-and-effect relationship between Parkinson’s and bacteria, one way or the other.

Fecal microbiome transplantation (FMT) is a category of procedures that aim to transplant fecal material — and, by extension, gut bacteria — from healthy individuals into sick people. The treatment is designed to put “good” bacteria back into the digestive tract, helping to replenish the bacterial balance.

In the new review, the researchers assessed the current state of evidence for the use of FMT, also called bacteriotherapy, and other gut-bacteria-targeted treatment strategies in Parkinson’s.

“FMT is an interesting option for restoring the changes in the microbiome of PD patients. It is an attractive technique because the administration is relatively simple and in general it has only a mild pattern of adverse effects,” Teus van Laar, MD, PhD, a professor at the University of Groningen, director of the Parkinson Expertise Center Groningen, and co-author of the review, said in a press release.

“However, no rigorous clinical trials have been performed yet, which leaves multiple questions open about the presumed optimal content of FMT, the route of administration, the volume of FMT and the long-term effects,” van Laar said.

There is virtually no available data on FMT in Parkinson’s, the researchers noted.

“References [in published scientific literature] to the potential use of FMT in PD are restricted to a recent Chinese case study on a PD patient with severe constipation,” they said. While this patient experienced improvement in both constipation and PD symptoms, it is virtually impossible to draw any conclusions from a sample size of one.

The researchers further noted that basic questions about using fecal transplant in PD still need to be addressed. For instance, FMT requires a “healthy’ donor” — but exactly what that means could be debated. This is especially true given that fact that the actual changes in gut microbiome that happen in PD aren’t fully understood.

Additionally, practical issues, like the best route — enema, nasogastric tube, etc. — or frequency of administration, will need to be worked out before FMT can be confidently recommended in PD.

The first clinical trial of FMT in 40 people with Parkinson’s (NCT03808389) is currently ongoing and is scheduled to be completed at the end of 2019. That trial, currently enrolling in Belgium, aims to recruit 40 Parkinson’s patients who will receive FMT from healthy donors while a control group receives autologous (self) FMT.

The results from this trial may help answer some of the questions researchers have about fecal transplant — in particular, whether it is beneficial at all for a significant portion of people with PD. However, many questions will remain unanswered following this study. For instance, the researchers noted that the inclusion criteria for Parkinson’s patients “do not in- or exclude constipation, which may complicate the interpretation of results.”

The researchers also pointed out that, while FMT is generally regarded as a low-risk procedure, there have been reported instances of serious — even fatal — complications. As such, the safety profile of fecal transplant in PD will need further evaluation.

The review also touched on other techniques used to influence gut bacteria, namely the use of probiotics and prebiotics. Probiotics are the “good” bacteria of the kind found in yogurt — though again, such definitions are highly subjective and context-dependent. Forms of fiber, prebiotics can help facilitate the growth of certain types of bacteria, rather than administration of the bacteria themselves.

Several studies have demonstrated that some kinds of probiotics — namely the bacteria groups Lactobacillus and Bifidobacterium — can help alleviate constipation in PD, the researchers said. However, whether these treatments have any effect on other symptoms of PD is currently unknown.

Prebiotics have not been tested in humans with Parkinson’s. The researchers noted that, in animal models of the disease, prebiotic treatment has “indicated beneficial effects on the PD symptoms.” Much more research will need to be done, however, to determine whether this has any bearing on human health.

“FMT is a black box with too many unanswered questions at the moment, also with respect to safety concerns,” van Laar said. “FMT or the use of pro- and prebiotics might become standard treatments in selected subgroups of PD patients in the future, but there are no good data yet in the public domain to support their use in PD patients.”

The researchers called for new studies investigating the use of such transplants in Parkinson’s.

“We hope this review will activate colleagues to start proper research on this topic as soon as possible, rather than to begin therapy without conclusive clinical data,” van Laar said.