Parkinson's disease affects all the nerve cells in the body, including the ones in the gut. The gut contains its own nervous system, the enteric nervous system, and can be thought of as a "second brain". This second brain can reflect what is going on in the actual brain. This study is being done to look for biomarkers, or early indicators of developing Parkinson's disease, in the microbiome and in the gut tissue taken during routine screening colonoscopy. People aged 45 and over who are due for their routine screening colonoscopy are eligible to participate.

Parkinson's disease affects 1 in 100 people over the age of 65, but the time between disease onset and diagnosis can be many months or years. Interestingly, the pathological hallmarks of Parkinson's disease and other synucleinopathies in the brain can also be seen in the nerve cells in the gut. Parkinson's disease may begin in the gut, at least in some people. Unlike the nerve cells in the brain, the nerve cells in the gut are accessible through routine colonoscopy, and so can be obtained by minimally invasive biopsy for the study in the laboratory. In addition, there are links between gut microbes, including bacteria, and the development of Parkinson's disease.

This research study is being done to discover whether the pathology in enteric nerve cells and the types of bacteria in the gut can serve as an indicator of Parkinson's disease. The goal of this research is to develop a biomarker that could help in earlier diagnosis. It also aims to improve the understanding of the link between the gut and brain in Parkinson's disease.

The American Cancer Society recommends screening colonoscopy starting from the age of 45 for the prevention of colon cancer. The study requires only one visit, and study samples will be collected as part of a colonoscopy needed for routine care.

Inclusion Criteria:

• Age 45-75 years old
• Parkinson's Disease defined by the modified UK Parkinson's Disease Society Brain Bank criteria, at risk for the development of Parkinson's disease including REM sleep behavior disorder and/or at least one first degree relative with PD or related disorder, and diseases related to Parkinson's disease including the synucleinopathies Lewy Body Dementia and Multiple System Atrophy.
• Baseline Hoehn & Yahr score 1-4
• No contraindications to undergoing screening colonoscopy
• Able to give informed consent for study participation

Exclusion Criteria:

• Clinical features suggestive of a neurodegenerative diagnosis other than synucleinopathy.
• Diagnosis of primary mitochondrial disorder, epilepsy, stroke, multiple sclerosis or other neurodegenerative diseases such as Alzheimer's disease, Progressive Supranuclear Palsy (PSP), and Corticobasal syndrome.
• Significant concomitant medical disease limiting life expectancy to less than 24 months from study inclusion, or significant and serious concomitant medical disease that is poorly controlled
• Signs of active malignant disease or other clinically relevant abnormality on chest x-ray
• Active or untreated gastrointestinal disease
• Inability to temporarily stop anti-platelet agents or other anti-coagulants without significant risk
• Known substance abuse (recent history of abuse of alcohol or other drugs such as barbiturates, cannabinoids and amphetamines) within last 5 years
• Contraindication to colonoscopy or associated anesthesia
• Pregnancy
• In the opinion of the investigator, any other condition regarded as making subject unsuitable for the study

Subjects with several stages of Parkinson's disease (PD), aged 45 to 75 years old and healthy age-matched control subjects