A recent study suggests that fecal transplants might influence the motor symptoms of individuals with Parkinson’s disease. In a small-scale clinical trial conducted at a single center in Belgium, participants with Parkinson’s disease who received a single dose of fecal transplant from a healthy donor showed better symptom improvement compared to those who received a placebo.
Findings published in eClinicalMedicine indicated that individuals who underwent a donor transplant experienced a motor score enhancement of 5.8 points after 12 months, contrasting with a 2.7-point enhancement among those who received a placebo transplant.
Moreover, notable enhancements were observed in an objective measure of constipation (colon transit time) despite the absence of significant variance in patient-reported constipation scores.
Mild gastrointestinal symptoms were common side effects noted during the transplant procedure, with a higher incidence observed among recipients of donor transplants. Additionally, individuals who received donor transplants were more prone to experiencing increased fatigue after the 12-month mark.
Fatigue: A Negative Side Effect of Fecal Transplantation?
Undertaken at the prestigious Ghent University Hospital, Belgium, the GUT-PARFECT trial, holds immense significance from December 1, 2020, to December 12, 2022. In this trial, 22 participants in the early stages of Parkinson’s disease were administered fecal transplants from healthy donors, while 24 received their fecal matter as a placebo.
The transplant, administered to both the treated and placebo groups, was delivered through the nasal passage via a tube inserted into the jejunum, a segment of the small intestine.
Researchers conducted follow-up assessments with participants at 3, 6, and 12 months post-transplantation. They gathered data on gastrointestinal symptoms, non-motor symptoms, depression and anxiety levels, sleep quality, fatigue, and cognitive function.
Although individuals who underwent fecal transplants from healthy donors showed enhancements in their motor symptoms, they reported increased fatigue.
Patrick Santens, MD, PhD, the study’s lead author and professor of neurology at Ghent University Hospital, remarked that the cause of this adverse effect remained uncertain.
“We lack a clear explanation for this phenomenon, but we suspect that inflammatory mechanisms may play a role. Fatigue is commonly seen in inflammatory gut disorders,” he informed us.
Can ‘placebo’ Fecal Transplants also Help?
One study limitation is the significant placebo effect observed, possibly due to the participants perceiving the placebo treatment as invasive.
Research indicates that the level of invasiveness of a placebo treatment correlates with the magnitude of the placebo effect.
Additionally, Santens suggested that some of the observed effects in the placebo group might not solely be attributed to the placebo effect.
“The placebo effect was extremely significant. On the one hand, this could be attributed to the nature of the treatment, which carries high expectations. On the other hand, preliminary research suggests that [fecal transplant] using one’s excrement may have a modest favorable effect, at least on gut function. In the following steps, we will try placebo treatment with colored inactive liquids”.
The Gut-Brain Axis in Parkinson’s Disease
Other trials of fecal transplants in patients with Parkinson’s disease have demonstrated modest improvements.
Herbert DuPont, MD, clinical professor of medicine specializing in infectious diseases at Baylor College of Medicine, Houston, TX, served as the primary author of a paper published in Frontiers In Neurology in 2023, indicating that fecal transplants may exert some influence on Parkinson’s disease symptoms.
Although he was not directly engaged in this recent study, when discussing its discoveries with a news platform, he clarified that disruptions to the microbiome in individuals with Parkinson’s disease have long been recognized. Furthermore, he highlighted diverse mechanisms through which the gut can impact Parkinson’s disease.
“One mechanism involves the central nervous system, where communication occurs via the vagus nerve to the enteric nervous system and spinal nerves leading to the brain, establishing direct neural connections,” he elaborated.
“The immune system is another pathway. The gastrointestinal tract contains 80% of the body’s immune cells, and our immune response is based on a healthy microbiome,” DuPont explained.
“And then the final thing is hormone production,” he said. “Chemicals, biochemicals, and metabolites generated by microorganisms travel through the circulation or the vagus nerve to the brain and exert an effect. These three routes are all quite significant.”
Braak’s Hypothesis of Parkinson’s Disease
In the context of this study, Braak’s hypothesis of Parkinson’s disease is pertinent. According to this hypothesis, Parkinson’s disease begins with the entry of a pathogen through the nose, which subsequently reaches the gut, triggering the accumulation of alpha-synuclein in both the nasal passages and the digestive system.
Certain researchers speculate that this accumulation then spreads to the nervous system and the brain, potentially leading to the development of Parkinson’s disease.
DuPont elaborated, stating, “We posit that neural pathways play a crucial role in transmitting alpha-synuclein, a small protein implicated in brain cell demise. This aligns with Braak’s hypothesis. However, biochemical factors and the immune system are also relevant.”
Single Dose of Fecal Matter could Improve Symptoms
DuPont emphasized the significance of demonstrating the long-lasting impact of a single dose of fecal transplant, stating, “I believed it was crucial to illustrate that even a solitary dose could yield lasting effects.”
He further explained, “I had assumed that for a chronic condition characterized by genetic abnormalities and enduring bodily changes, multiple administrations would be necessary to evoke a response, as has been the approach in our previous studies. However, this study indicates that even a single dose can provoke a notable effect.”
Administering multiple doses might require delivering the transplant through capsules, potentially entailing a process that could compromise numerous beneficial cells, microorganisms, enzymes, and biochemicals within the fecal matter.
In previous research conducted by DuPont, various types of fecal matter, including fresh, frozen, and freeze-dried samples, were examined. “This study has inspired me to consider the possibility of using frozen or fresh samples in future trials,” DuPont shared with us.
He further speculated, “I believe the studies on Parkinson’s disease could pave the way for similar research into other neurodegenerative disorders. Conditions such as multiple sclerosis and Alzheimer’s may also see similar success stories in the future.”
Santens informed us that the team responsible for the recent study is delving deeper into the participants’ microbial compositions to understand their correlation with the study outcomes.
“We are aiming to secure funding for a larger, multicenter trial that integrates the insights gained from this pilot study,” he stated. “Additionally, we are exploring patient profiles to identify potential subgroups that could benefit most from this treatment.”
Reference
Stool transplant could improve motor symptoms in Parkinson’s disease [Internet]. MedicalNewsToday (Accessed on April 30, 2024). Available at: https://www.medicalnewstoday.com/articles/stool-transplant-could-improve-motor-symptoms-in-parkinsons-disease
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