A small new trial suggests that stool transplants could be a helpful treatment option in early-stage Parkinson’s disease.
- 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.
Fatigue: A
negative side effect of fecal transplantation?
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.
Can
‘placebo’ fecal transplants also help?
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.”
The
gut-brain axis in Parkinson’s disease
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.”
Braak’s
hypothesis of Parkinson’s disease
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.”
Single
dose of fecal matter could improve symptoms
“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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