Gut-Brain Connection in Parkinson's Disease

Inclusion Criteria (All PD Cohorts) 1. Aged ≥21 years old and ≤80 years old 2. Clinical diagnosis of PD as defined by Movement Disorder Society (MDS) PD Criteria 3. Adequate visual, hearing, cognitive, and physical ability 4. Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures. Because longitudinal participation is important to the scientific goals of the program, a "best estimate" of interest, commitment, and geographic feasibility for three years will be documented by the enrolling investigator after interview with the potential enrollee Inclusion Criteria Controls 1. Aged ≥21 years old and ≤80 years old 2. No known or diagnosed neurodegenerative disease 3. Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures 4. Resides within the same household as person with PD Inclusion Criteria Prodromal Cohort 1. Aged ≥21 years old and ≤80 years old 2. Prodromal characteristics are defined by the MDS Research Criteria for PD and include either polysomnography (PSG)-confirmed rapid eye movement sleep behavior disorder (RBD) or possible RBD (questionnaire-based), with hyposmia as defined by the University of Pennsylvania Smell Identification Test (UPSIT) ≤ 15th percentile. Exclusion Criteria (All Cohorts) 1. Diagnosis of secondary or atypical parkinsonism 2. Laboratory Values: 1. Hemoglobin (Hgb) \<10 2. Platelets \<70,000 3. Alanine Transaminase (ALT) or Aspartate Aminotransferase (AST) \> 2 1/2 times upper limit of normal (ULN) 4. Moderate or severe renal disease with an estimated glomerular filtration rate (eGFR) \<60 mL/min/BSA \[body surface area\]) calculated using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation, or moderate or severe hepatic impairment (alkaline phosphatase \[ALP\] \>2.0 times the ULN and/or total bilirubin \>2.0 times the ULN) 5. Significantly above the normal range for PT/INR/PTT 3. Currently taking anticoagulants that are deemed exclusionary by the investigator for risk of bleeding with sigmoidoscopy procedure 4. Clinically significant cognitive impairment with a Montreal Cognitive Assessment (MOCA) score \<22 5. Clinical or laboratory findings consistent with another primary neurodegenerative disease or cognitive disorder other than PD, including but not limited to, frontotemporal lobar disease, Huntington's disease, progressive supranuclear palsy, multisystem atrophy, Creutzfeld-Jakob- Disease, Down's syndrome, cortico-basal degeneration, dementia with Lewy Bodies, Alzheimer's disease, amyotrophic lateral sclerosis, seizure disorder, stroke, or other infectious, metabolic, or systemic disease affecting the central nervous system including, but not limited to, syphilis, present hypothyroidism, present or unaddressed/treated vitamin B12 deficiency, or other screening laboratory abnormalities 6. Suicidality, defined as active suicidal thoughts or ideation within 6 months before Screening or at Baseline, defined as answering yes to items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS), or history of suicide attempt in previous 2 years, or, in the Investigator's opinion, at serious risk of suicide 7. Has cancer or has had a malignant tumor within the past 5 years. (Participants with stable untreated prostate cancer or treated/removed cutaneous carcinomas are not excluded.) 8. Any medical condition or systemic disease that, in the Investigator's opinion, may either put the participant at risk because of participation in the study, influence the results or proposed analyses, or impair the participant's ability to fully participate in the study 9. Body mass index (BMI) \>35 kg/m2 or body weight \<50 kg 10. Participant is currently pregnant, breastfeeding, and/or lactating 11. History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria) 12. History of Covid 19 (SARS-CoV-2) infection within 6 weeks prior to screening. 13. Participants with unresolved symptoms of Covid 19 infection or ongoing cognitive or other deficits attributable to post-Covid 19 that may affect participant safety or interfere with cognitive assessments based on the Investigator's clinical judgment 14. Either ongoing or current participation in another clinical trial with an investigational agent and have taken at least one dose of study medication, unless unblinded on placebo, within 4 weeks prior to the start of screening, or five half-lives of the investigational drug, whichever is greater. The end of a previous investigational trial is the date the last dose of an investigational agent was taken. Participation in other research studies (e.g., observational studies) may be acceptable throughout this study. 15. History of GI surgery. (However, patients with appendicectomy, hemorrhoid surgery, and cholecystectomy will be eligible to participate). 16. Regular use of medication that impacts the intestinal barrier (e.g., NSAID more than 3 times weekly) 17. Has a history of Crohn's disease, ulcerative colitis, and/or other types of colitis (microscopic, lymphocytic, or collagenous colitis). Confirmed diagnosis of inflammatory bowel disease (IBD) and/or, active or uncontrolled IBD symptoms such as diarrhea, bleeding, or severe stomach pain. Treatment for IBD in the past 6 months with medicines such as steroids, biologics, or strong immune-suppressing drugs. Surgery to remove part of the bowel due to IBD. Other long-term gut diseases that cause inflammation, such as celiac disease.