Fecal microbiota transplantation (FMT) is an effective and safe treatment for Clostridioides difficile infection (CDI). Though CDI is the only indication for FMT, more and more preliminary data on FMT in neurological disorders are reported due to gut-brain axis. This study is a pilot study to apply FMT on patients with Parkinson's disease (PD). The effect of FMT on motor and non-motor symptoms in PD will be also evaluated.

1. Screening and Enrollment Participants will be recruited from movement disorders clinics at Chang Gung Memorial Hospital (CGMH). Written informed consent will be obtained prior to study participation. Control group participants will undergo the same evaluation protocol as the treatment group, except for fecal microbiota transplantation (FMT).

2. Clinical Assessments Before the baseline visit, participants will complete a 3-day diary documenting motor symptoms, non-motor symptoms, and medication timing. At each visit, neurological examinations and standardized Parkinson's disease (PD) assessments will be performed.

   Adverse events (AEs) and serious adverse events (SAEs) will be recorded throughout the study, regardless of causality, and categorized by their relationship to FMT.

   Follow-up assessments will be conducted at 1 week, 3 months, and 6 months after FMT. Stool samples will be collected at baseline, 3 months, and 6 months.

3. Donor Screening and Specimen Processing Healthy donors will undergo comprehensive screening, including medical history, risk assessment, and laboratory testing, in accordance with national FMT consensus guidelines. Eligible donors will provide stool samples under standardized conditions.

   Samples will be processed at the CGMH microbiota center following established protocols, including preparation for microbiome and metabolite analyses (e.g., short-chain fatty acids) using validated laboratory methods such as gas chromatography-mass spectrometry (GC-MS). Blood samples from participants will also be collected and stored for analysis.

4. Clinical Outcome Measures

   Assessments will include:

   Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS, on/off medication) Hoehn and Yahr stage Levodopa equivalent daily dose (LEDD) Motor complications (3-day diary) Montreal Cognitive Assessment (MoCA)

   Patient-reported outcomes:

   Wearing-Off Questionnaire (WOQ-9) Parkinson's Disease Questionnaire (PDQ-39) SENS-PD (non-dopaminergic symptoms) Parkinson's Disease Constipation Questionnaire (PDCQ)

5. FMT Procedure Participants in the treatment group will receive oral vancomycin (125 mg every 6 hours for 3 days) and follow a low-fiber diet prior to FMT. After bowel preparation and a 24-hour washout period, processed donor microbiota will be delivered to the terminal ileum or cecum via ileocolonoscopy. Participants will remain in the right lateral position for at least 30 minutes post-procedure.

6. Specimen Storage All collected specimens will be stored at -80°C at the microbiota center until study completion. Residual samples will be transferred to the institutional biobank or destroyed according to participant consent.

7. Transportation Microbiota preparations will be transported under controlled temperature conditions. For intra-hospital use, samples will be delivered immediately with cold-chain protection. For inter-hospital transport, samples will be frozen at -80°C, shipped on dry ice, and used on the day of arrival or stored for up to 180 days.

8. Quality Control and Follow-up All procedures, including donor selection, sample processing, and patient care, will follow national FMT consensus guidelines. Participants will be monitored at scheduled follow-ups (1 week, 3 months, and 6 months), with additional assessments arranged as needed to ensure safety and data completeness.

Inclusion Criteria:

1. Clinical diagnosis of idiopathic PD according to UK brain bank criteria.
2. PD disease duration ≧5 years to avoid the possible misdiagnosis of atypical parkinsonism.
3. Hoehn-Yahr stage 1-4
4. Using levodopa in a currently fixed dose.
5. Presence of motor complications (motor fluctuation or dyskinesia).
6. Written informed consent.
7. Age above 18.

Exclusion Criteria:

1. Hoehn-Yahr stage 5. (wheelchair ridden or bedridden due to PD)
2. Dementia (MMSE<24), history of encephalitis, or brain organic lesions, including congenital or acquired structural abnormalities (which were detected through brain computed tomography scan or Magnetic Resonance Imaging) may affect neurological function, leading to various neurological deficits and mpairing the cognitive function.
3. Current use of probiotics or in the past 3 months.
4. For women with childbearing potential. (Female participants are suggested to prevent pregnancy during this trial and undergo a pregnancy test before enrollment.)
5. Current need of antibiotics or use in the previous 3 months.
6. End stage renal disease caused uremic encephalopathy or liver cirrhosis caused hepatic encephalopathy
7. Immunocompromised state.