Untreated Parkinson's Disease Work-up Assessing Resident Microbiota and Duodenal Barrier Function

This is a hypothesis-generating study aimed at characterising gut microbiome composition and intestinal permeability in patients with drug-naïve Parkinson's disease (PD), compared to age-matched healthy controls (HCs). Drug-naïve PD patients and HCs will be prospectively recruited. After a screening visit, participants will undergo a single study visit; no longitudinal follow-up is planned.

Participants will undergo standardized assessments across five domains: (1) gut microbiome and fecal read-outs, (2) duodenal barrier function assessed using optional duodenal biopsies, (3) whole-gut transit time measured with radiopaque markers, (4) clinical features assessed using validated questionnaires and rating scales, and (5) laboratory parameters obtained from blood sampling.

For the main study procedures (stool collection, radiopaque pellet ingestion with abdominal X-ray, clinical assessments, questionnaires, and blood sampling), approximately 75 drug-naïve PD patients will be included. Approximately one third are expected to consent to the optional gastroduodenoscopy, resulting in an estimated subgroup of 25 PD patients with duodenal biopsies. Age-matched healthy controls will be recruited in comparable numbers for the respective study components. All analyses will be cross-sectional.

• Inclusion criteria:

Patients eligible for inclusion in this study must meet all of the following criteria:

• Diagnosis of Parkinson's Disease by a neurologist according to the Movement Disorder Society Clinical Diagnostic Criteria for PD
• Signed informed consent form
• Aged 18-75 years old
• Able to understand the study and questionnaires, and comply with study requirements

Controls eligible for inclusion in this study must meet all of the following criteria:

• Aged 40-75 years old
• Signed informed consent form
• Able to understand the study and questionnaires, and comply with study requirements

• Exclusion criteria:

Participants eligible for this study must not meet any of the following criteria:

Patients and controls:

• Gastrointestinal: diagnosis of organic gastrointestinal diseases potentially affecting the assessments during the study (e.g. inflammatory bowel disease (IBD), celiac disease, eosinophilic diseases of the gastro-intestinal tract, gastro-intestinal cancer, diverticulitis in the last 6 months, GI infection in the last 3 months, …).
• Surgery: major abdominal surgery (including, but not limited to: cholecystectomy, colectomy, hiatal hernia repair, …) except for uncomplicated appendectomy, splenectomy and inguinal hernia repair.
• Medication use:

• Any previous exposure to medication used in the treatment of motor symptoms of Parkinson's disease (levodopa, dopamine agonists, MAO-B inhibitors, COMT-inhibitors, NMDA-receptor antagonists, anticholinergics)
• Antibiotics use in the last 3 months.
• Use of PPI in the last month.
• Use of NSAID in the last month.
• Use of anticoagulation4 (including vitamin K antagonists (VKA), direct oral anticoagulants (DOAC) or low-molecular weight heparins (LMWH)) or dual antiplatelet therapy4 (DUAPT; Acetylsalicilic acid (Asaflow®) + P2Y12-inhibitor (Clopidogrel®)).
• Pregnancy and breastfeeding.
• Other: Cancer and/or adjuvant treatment within the last 6 months
• Exposures:

• Food intoxication in the last 3 months.
• Consumptom of more than 2 standard units of alcohol per day.

Patients (additional criteria)

• Neurological: any major neurological disorder other than Parkinson's disease.

Controls (additional criteria)

• Neurological:

• A diagnosis of Parkinson's disease or any other major neurological disorder other than Parkinson's disease.
• Clinical signs of parkinsonism.
• First degree relative(s) with Parkinson's disease.
• Gastrointestinal: subjects fulfilling a clinical diagnosis of either Functional dyspepsia, Functional constipation, or Irritable bowel syndrome based on the ROME-IV diagnostic criteria.