GBPDC: Gut-Brain in PD Consortium Master Protocol

The purpose of this research study is to identify the role that the gut-brain axis, the group of nerves that connect the brain and gut, plays in Parkinson's disease (PD). The National Institute of Diabetes and Digestive and Kidney Diseases is sponsoring this research study. During this study, specific groups of participants, also known as "cohorts", will be identified based on the severity of their PD. There will also be a cohort enrolling participants who do not have Parkinson's and a cohort enrolling participants that are at risk for developing PD. Each of these cohorts will be compared to the others to assess the differences in the gut-brain connection. Participants in this study will: * meet with a medical provider * answer questionnaires * give samples of blood, stool, and saliva * have X-rays taken while swallowing different foods (swallowing study) * have X-rays taken to see how long it takes markers to move through their colon (colon transit study) * have a flexible sigmoidoscopy, where a doctor looks inside the lower part of the colon and takes small tissue samples (biopsies) from the mucosa (lining) * have samples taken of their skin * have an anorectal manometry and a balloon expulsion test, where a small tube and balloon are placed in the rectum to measure muscle function. Participation in the study will last up to 24 months (2 years).

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) \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 \35 kg/m2 or body weight \