Single-dose stool transplant could improve symptoms

By Staff 9 Min Read

  • Parkinson’s disease is one of the leading causes of disability worldwide, and while treatment options are available, they can become less effective over time.
  • A recent paper has highlighted the potential effect of fecal transplants on motor symptoms, which are one of the main markers of Parkinson’s disease.
  • The study could pave the way for further research into the role of the gut microbiome on neurodegenerative conditions, say experts.

Fecal transplants could have an effect on the motor symptoms of people with Parkinson’s disease, a recent study suggests.

A small, single-center clinical trial carried out in Belgium found that people with Parkinson’s disease who received a single dose of a fecal transplant from a healthy donor, had improved symptoms compared to those who received a placebo.

Results, published in eClinicalMedicine, suggested that the motor score for people who received a donor transplant had improved by 5.8 points after 12 months, compared with an improvement of 2.7 points in people who received a placebo transplant.

Significant improvements were also found for an objective measure of constipation (colon transit time), although there was no significant difference in patient-reported scores for constipation.

Mild gastrointestinal symptoms were a common negative side effect at the time of the transplant and were more frequently observed in people who received the donor transplant. Donor transplant recipients were also more likely to have worsened fatigue after 12 months.

For the study, a total of 22 participants with early-stage Parkinson’s disease received the transplants from healthy donors, and 24 received their own fecal matter as a placebo, as part of the GUT-PARFECT trial carried out at Ghent University Hospital, Belgium between December 1, 2020 and December 12, 2022.

The fecal transplant for both the treated cohort and the placebo cohort was delivered via a tube inserted in the jejunum, a part of the small intestine, via the nose.

Researchers followed up with the participants at 3, 6 and 12 months post-transplant. They collected data on gastrointestinal symptoms, non-motor symptoms, depression and anxiety, sleep and fatigue, and cognition.

While people who received fecal transplants from healthy donors registered improvements in their motor symptoms, they appeared to experience increased fatigue.

The reason for this negative effect was unclear, said lead author of the study Patrick Santens, MD, PhD, professor of neurology at Ghent University Hospital.

“We don’t have a good explanation [for this phenomenon], but suspect that inflammatory mechanisms may be involved. Fatigue is prevalent in inflammatory gut disorders,” he told Medical News Today.

One of the limitations of the study is that a strong placebo effect was observed, potentially because the placebo treatment was likely to have been viewed as invasive by the participants.

There is evidence to suggest that the more invasive a placebo treatment is, the greater the placebo effect.

It was also possible that some of the effect seen in the placebo group, was not just placebo effect, Santens suggested:

“The placebo effect was quite large. This may be due to the nature of the treatment with large expectations, on the one hand. On the other hand, there is preliminary evidence that [fecal transplant] with one’s own stool might also have a limited positive effect, at least on gut function. Therefore, we will try placebo treatment with colored inactive solutions in the next steps.”

Small improvements have been seen in other trials of fecal transplants in Parkinson’s disease patients.

Herbert DuPont, MD, clinical professor of medicine – infectious disease at Baylor College of Medicine, Houston, TX was the first author of a paper published in Frontiers In Neurology in 2023, which showed that fecal transplants could have some effect on the symptoms of Parkinson’s disease.

He was not involved in this latest research, but in commenting on its findings for MNT, he explained that disturbances to the microbiome in Parkinson’s disease patients have been known about for years, and there are various ways in which the gut can affect Parkinson’s disease.

“One is through the central nervous system, through the vagus nerve to the enteric nervous system through spinal nerves to the brain, and that’s direct neural connections.“ he said.

“The other way is through the immune system. Eighty percent of immune cells of the body are in the gastrointestinal tract, and our immune response is dependent on a healthy microbiome,“ DuPont added.

“And then the final thing is hormone production,“ he told us. “Chemicals, biochemicals and metabolites produced by the microbes go through the bloodstream or through the vagus nerve to the brain and have an effect. These three routes are all very important.”

Relevant to the context of this research is Braak’s hypothesis of Parkinson’s disease, which proposes that Parkinson’s disease starts to develop when a pathogen enters the body through the nose, reaches the gut, and initiates the accumulation of alpha-synuclein in the nose and the digestive tract.

Some researchers think that this then spreads to the nervous system and brain, potentially causing Parkinson’s disease.

DuPont explained:

“We believe that neural connections are very important in the movement of alpha-synuclein, the small protein that is involved in producing cell death in the brain. And this is the so-called Braak’s hypothesis. And I think this is correct, but I think the biochemicals are very important. And I think the immune system is very important.”

“I thought [it] was very important to show that a single dose [fecal transplant] could have a durable effect,“ DuPont told us, commenting on the study findings.

“I felt if it was a chronic disease where there are genetic disorders and chronic changes in the body then you would have to give [fecal matter] multiple times to have an effect and that’s been the way we’ve done our studies. But this shows that [even] one dose will have an effect,” he added.

Multiple dosing may necessitate providing the transplant via capsules, for example, which would involve processing the fecal matter in a way that might destroy many of the cells, microorganisms, enzymes and biochemicals that could be beneficial.

Previous research conducted by DuPont looked at transplants carried out with fresh, frozen, and freeze-dried fecal matter. “This study has given me an encouragement to think about giving, maybe, frozen or fresh samples in the future,“ DuPont told us.

“I think the Parkinson’s studies are a lead into [similar research for] other neurodegenerative disorders. Multiple sclerosis and Alzheimer’s may well follow, and may well have a similar success story,” he hypothesized.

Santens told us that the team behind the latest study was conducting further research into the microbial compositions of the different participants in relation to the recent study outcomes.

“We hope to get funding for a larger and multicenter trial, taking into account the findings of this pilot trial […] We are also looking at patient profiles to potentially delineate subgroups that might be optimal candidates for this treatment,” he told us.

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