Parkinson’s Disease: Recent developments in Fecal Microbiota Transplant

Introduction

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects millions of people worldwide. Although less prevalent than Alzheimer’s disease, Parkinson’s disease represents a growing public health challenge. Epidemiological estimates suggest that approximately 1 in 100 individuals over the age of 60 will develop PD, with prevalence rising sharply with advancing age [1].

Parkinson’s disease is clinically characterized by a constellation of motor symptoms, including resting tremor, muscle rigidity, bradykinesia (slowness of movement), impaired balance, and gait disturbances. These symptoms can substantially interfere with daily activities and reduce quality of life. Diagnosis is primarily clinical, based on neurological examination and the observation of hallmark motor features such as tremor, rigidity, postural instability, impaired coordination, and speech difficulties [2]. In some cases, diagnostic confidence is strengthened by a positive response to dopaminergic therapy, particularly levodopa, a dopamine precursor commonly used in PD management.

The underlying neuropathology of Parkinson’s disease involves the progressive degeneration of dopamine-producing neurons in the substantia nigra, a midbrain structure critical for motor control. Dopamine serves as a key neurotransmitter that enables smooth and coordinated communication between brain regions responsible for voluntary movement. Loss of dopaminergic signaling disrupts this circuitry, leading to the motor impairments that define Parkinson’s disease [3].

Although the precise etiology of PD remains unknown, both genetic susceptibility and environmental factors are believed to contribute to disease development. Mutations in several genes have been linked to familial forms of Parkinson’s disease, though these account for only a small proportion of cases. Environmental exposures—such as certain herbicides, pesticides, medications, and toxins—as well as a history of head trauma have also been implicated as potential risk factors. Accordingly, established risk factors for PD include advancing age, genetic predisposition, environmental exposures, medication use, and prior head injuries [4,5].

At present, there is no cure for Parkinson’s disease. Available treatments are aimed at alleviating symptoms and improving functional capacity. Levodopa remains the cornerstone of therapy, often combined with other pharmacological agents, physical therapy, and, in selected cases, surgical interventions. However, the effectiveness of levodopa may diminish over time, and long-term treatment can be associated with motor complications.
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Intensive research efforts continue to explore disease-modifying strategies. Emerging approaches include gene therapy, cell-based therapies using dopaminergic stem cells, and deep brain stimulation, which delivers targeted electrical impulses to specific brain regions to improve motor function [6]. In recent years, another promising and rapidly evolving area of investigation has emerged: the role of the gut microbiome in Parkinson’s disease and the potential therapeutic application of fecal microbiota transplantation (FMT). Growing evidence suggests that alterations in gut microbial composition may influence neuroinflammation, α-synuclein pathology, and disease progression, positioning the gut–brain axis as a novel target for future PD therapies.

References
[1] Who has Parkinson’s?
[2] Getting diagnosed
[3] Diagnosis & treatment of Parkinson’s disease
[4] Parkinson’s disease risk factors and causes
[5] 5 risk factors for Parkinson’s diseases
[6] Parkinson’s Disease-Clinical Research

The Parkinson’s Disease Microbiome

Microbiome definition re-visited: old concepts and new challenges. Berg G. et al. Microbiome (2020) 8:103
Figure 2

Over the past decade, a growing number of studies have reported significant gut microbiome dysbiosis in Parkinson’s disease (PD) when compared with healthy controls. While individual studies have produced variable results—largely due to differences in sampling methods, sequencing platforms, geographic populations, and study design—recent meta-analyses and large-scale metagenomic studies have converged on a more consistent and biologically plausible microbial signature associated with PD [1–3]. The following summary reflects these findings without overinterpretation.

Core Features of Gut Dysbiosis in Parkinson’s Disease

A hallmark of the PD-associated microbiome is a shift from dominant, health-associated taxa toward lower-abundance, pro-inflammatory species. This pattern is characterized by a depletion of several key bacterial groups known to support intestinal and neurological health, accompanied by an expansion of taxa with uncertain or potentially pathogenic roles.

Depletion of Short-Chain Fatty Acid–Producing Bacteria

Several consistently depleted taxa in PD belong to bacterial groups responsible for the production of short-chain fatty acids (SCFAs)—particularly butyrate, a metabolite essential for maintaining gut barrier integrity, regulating immune responses, and supporting the enteric nervous system.

Notably reduced genera include:

• Roseburia, Fusicatenibacter, Blautia, and Anaerostipes (family Lachnospiraceae)
• Faecalibacterium (family Ruminococcaceae)
• Members of the Butyricicoccaceae family

The depletion of these SCFA-producing bacteria has also been observed in individuals with gastrointestinal disorders, chronic inflammatory conditions, and other neurodegenerative or neuroinflammatory diseases, suggesting a shared pathological pathway involving impaired gut–brain communication.

Enrichment of Specific Bacterial Taxa in PD

In contrast, several bacterial genera show increased abundance in the gut microbiota of PD patients, including:

• Lactobacillus
• Bifidobacterium
• Akkermansia
• Hungatella

The enrichment of Lactobacillus and Bifidobacterium is particularly intriguing, as these genera are commonly regarded as beneficial and are widely used in probiotic formulations. Whether their increased presence contributes to disease mechanisms or reflects adaptation to a pro-inflammatory gut environment remains unclear.

The role of Akkermansia species is especially complex. While Akkermansia muciniphila is often considered metabolically beneficial and has been investigated as a probiotic for metabolic disorders [4], its association with Parkinson’s disease appears geographically variable and inconsistent across studies [3]. Some Akkermansia species degrade mucin, potentially thinning the intestinal mucus layer and impairing gut motility. This mechanism may contribute to constipation, a common and early non-motor symptom of PD.

Additionally, increased abundance of the Christensenellaceae family has been reported in PD. These bacteria produce hydrogen, which supports the growth of Methanobrevibacter, a hydrogenotrophic archaeon responsible for methane production in the gut. Elevated methane levels are known to slow intestinal transit and may further exacerbate constipation in Parkinson’s disease.

Functional and Metabolic Alterations in the PD Gut Microbiome

Beyond taxonomic changes, functional profiling of the PD microbiome reveals profound alterations in metabolic and inflammatory pathways. These include:

• Increased production of pro-inflammatory bacterial components, such as:
  • Lipopolysaccharides (LPS)
  • Lipoteichoic acid (LTA)
  • Murein and bacterial lipoproteins (BLP)
• Dysregulation of proteolytic and amino acid degradation pathways
• Altered synthesis and metabolism of key neurotransmitters, including:
  • Dopamine
  • Glutamate
  • Gamma-aminobutyric acid (GABA)
  • Serotonin

Importantly, metagenomic analyses have also identified upregulation of microbial pathways involved in the degradation of nicotinamide and trehalose, both of which possess neuroprotective properties. In addition, pathways responsible for the production of curli, a bacterial amyloidogenic protein, are enriched in PD-associated microbiota. Curli may promote α-synuclein aggregation, a pathological hallmark of Parkinson’s disease.

Further concern arises from the increased capacity of the PD microbiome to produce trimethylamine (TMA), a precursor of trimethylamine N-oxide (TMAO), a metabolite linked to cardiovascular disease and stroke—comorbidities frequently observed in PD patients [3].
Collectively, these functional alterations favor a pro-inflammatory, neurodegenerative intestinal environment, supporting the hypothesis that gut dysbiosis contributes to Parkinson’s disease pathogenesis alongside genetic susceptibility, environmental exposures, and aging.

From Microbiome Insights to Therapeutic Interventions

Advances in microbiome research have catalyzed efforts not only to better understand disease mechanisms but also to identify microbiome-based biomarkers and develop therapeutic interventions aimed at modifying disease progression.

Clinical studies investigating probiotics in Parkinson’s disease have demonstrated modest benefits, particularly in improving gastrointestinal symptoms such as constipation, though effects on motor symptoms remain limited [5,6].

More notably, growing evidence supports the therapeutic potential of fecal microbiota transplantation (FMT). By restoring a healthier microbial ecosystem, FMT aims to correct dysbiosis at its source. Early clinical trials and observational studies have reported encouraging outcomes, positioning FMT as one of the most promising microbiome-based interventions currently under investigation for Parkinson’s disease.

References
 [1] Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation. Romano S, Savva GM, Bedarf JR, Charles IG, Hildebrand F and Narbad A. npj Parkinson’s Disease (2021) 7:27; https://doi.org/10.1038/s41531-021-00156-z.
[2] Inflammatory microbes and genes as potential biomarkers of Parkinson’s disease. Nie S, Wang J, Deng Y, Ye Z and Ge Y. npj Biofilms and Microbiomes (2022) 8:101; https://doi.org/10.1038/s41522-022-00367-z.
[3] Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms. Wallen ZD, Demirkan A, Twa G, Cohen G, Dean MN, Standaert DG, Sampson TR & Payami H. Nature Communications (2022) 13:6958.
[4] A Critical Perspective on the Supplementation of Akkermansia muciniphila: Benefits and Harms. Chiantera, V.; Laganà, A.S.; Basciani, S.; Nordio, M.; Bizzarri, M. Life (2023) 13, 1247. https://doi.org/10.3390/life13061247
[5] Probiotics and Parkinson’s Disease: What You Need To Know. Emily Wagner, M.S. August 17, 2023
[6] Probiotics and the Treatment of Parkinson's Disease: An Update. Mirzaei, H., Sedighi, S., Kouchaki, E. et al.  Cell Mol. Neurobiol (2022) 42, 2449–2457. https://doi.org/10.1007/s10571-021-01128-w

Fecal Microbiota Transplantation (FMT) in Parkinson’s Disease

Fecal microbiota transplantation (FMT) involves the transfer of processed stool from a healthy donor to a recipient with the goal of restoring a balanced and functional gut microbiome. Originally developed to treat recurrent Clostridioides difficile infection, FMT has recently emerged as a promising investigational therapy for Parkinson’s disease (PD), driven by growing evidence linking gut dysbiosis to neurodegeneration.

Early Clinical Evidence and Proof of Concept

Interest in FMT for Parkinson’s disease was first sparked in 2019, when Huang et al. reported a case study of a 71-year-old PD patient who experienced notable improvement in constipation and motor symptoms following FMT [1]. Although anecdotal, this report provided an important proof of concept and catalyzed further clinical investigation.

Subsequent observational studies and early-phase clinical trials began to systematically assess the safety, feasibility, and therapeutic potential of FMT in PD. A pivotal pilot study by Kuai et al. in 2021 evaluated 11 PD patients with constipation who received a single FMT via nasoduodenal tube [2]. In addition to significant relief of gastrointestinal symptoms, patients demonstrated measurable improvements in motor function and quality of life, suggesting effects beyond the gut.

These findings were reinforced by two independent clinical trials using oral, lyophilized encapsulated FMT:

• A small randomized, placebo-controlled pilot study involving 12 PD patients who received FMT capsules twice weekly for 12 weeks [3]
• A larger randomized study of 56 PD patients treated once weekly for three weeks [4]

Together, these studies consistently reported improvements in constipation, motor symptoms, and patient-reported outcomes, supporting the hypothesis that microbiome modulation via FMT may influence both motor and non-motor manifestations of Parkinson’s disease.


Methodological Challenges and Knowledge Gaps

Despite encouraging early results, these initial studies shared several limitations. Most were constrained by small sample sizes, short follow-up periods, and heterogeneous patient populations. In addition, significant variability existed in donor selection, stool processing methods, dosing frequency, and routes of administration (e.g., nasoenteric vs. oral delivery), complicating cross-study comparisons.

Importantly, the long-term safety, durability of clinical benefit, and optimal dosing regimens of FMT in Parkinson’s disease remain unresolved. These uncertainties underscore the need for larger, well-controlled trials and have been highlighted in recent systematic reviews of the field [5].


The Shift Toward Rigorous Randomized Controlled Trials

​In response to these challenges, the field has increasingly shifted toward rigorous randomized controlled trials (RCTs) designed to establish both efficacy and safety. A major milestone was achieved with the recent publication of the GUT-PARFECT trial, a single-center, randomized, double-blind, placebo-controlled phase 2 study involving 46 patients with early-stage Parkinson’s disease [6].

In this trial, patients receiving a single FMT via nasojejunal administration demonstrated significantly greater improvements in motor symptoms compared with placebo-treated participants. The study provided the strongest clinical evidence to date supporting the therapeutic potential of FMT in PD and marked a critical step toward clinical validation.

Remaining Challenges and Future Directions

Despite these advances, several hurdles must be overcome before FMT can be considered a mainstream therapeutic option for Parkinson’s disease. Key priorities include:

• Large-scale, multicenter RCTs with longer follow-up to confirm efficacy, safety, and durability
• Standardization of FMT protocols, including donor screening, stool preparation, and administration routes
• Mechanistic studies to clarify how microbiome modulation influences neuroinflammation, α-synuclein pathology, and gut–brain signaling

Addressing these challenges will be essential to reduce variability, enhance reproducibility, and identify patient subgroups most likely to benefit from microbiome-based interventions.


Conclusion: The Promise of Microbiome-Based Therapies in Parkinson’s Disease

Fecal microbiota transplantation represents a novel and rapidly evolving therapeutic strategy for Parkinson’s disease, with the potential to alleviate both motor and non-motor symptoms by targeting the gut–brain axis. From early case reports to well-designed randomized trials, the trajectory of FMT research highlights the transformative promise of microbiome-based therapies.

​While important questions remain, continued investment in high-quality clinical research and mechanistic studies may ultimately position FMT—or refined microbiota-derived therapies—as part of a new generation of disease-modifying treatments for Parkinson’s disease.

References
[1] Fecal microbiota transplantation to treat Parkinson's disease with constipation: A case report. Huang H et al. Medicine (2019) 98(26): p e16163. DOI: 10.1097/MD.0000000000016163
[2] Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation. Kuai X et al.  Microb. Cell Fact. (2021) 20, 98. https://doi.org/10.1186/s12934-021-01589-0
[3] Fecal microbiota transplantation in Parkinson's disease—A randomized repeat-dose, placebo-controlled clinical pilot study. DuPont HL et al. Front. Neurol. (2023) 14:1104759. doi: 10.3389/fneu  r.2023.1104759
[4] Efficacy of fecal microbiota transplantation in patients with Parkinson’s disease: clinical trial results from a randomized, placebo-controlled design. Cheng Y et al. Gut Microbes (2023), 15(2), 2284247. https://doi.org/10.1080/19490976.2023.2284247
[5] The Potential Role of Fecal Microbiota Transplantation in Parkinson’s Disease: A Systematic Literature Review. Vongsavath T et al. Appl. Microbiol. (2023) 3, 993–1002. https://doi.org/10.3390/applmicrobiol3030067
[6] Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson’s disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial. Bruggerman A et al. eClinical Medicine (2024) 71: 102563. https://doi.org/10. 1016/j.eclinm.2024. 102563

Looking forward

Living with Parkinson’s disease presents daily physical and emotional challenges. Yet, sustained progress in neuroscience, microbiome research, and clinical innovation—supported by collaboration among clinicians, researchers, patients, and private-sector stakeholders—offers renewed hope. As our understanding of Parkinson’s disease deepens, microbiome-targeted therapies such as FMT may contribute meaningfully to improved disease management and, ultimately, to the pursuit of curative strategies.