Levodopa (LD) is an effective treatment to control symptoms of Parkinson's disease (PD). However, the response to (the effectiveness) LD changes over time and patients require higher and more frequent LD doses for treatment. The purpose of this study is to identify what reasons or causes might influence the changes in LD effectiveness, particularly if intestinal bacteria contribute to the breakdown of LD in patients with PD. This study is an observational cohort proof-of-concept study that follows PD patients who take PD at high-frequency doses and low-frequency doses. . Each PD patient will have a household healthy control/spouse enrolled into the study. Single patients with no spouse will still be eligible to enroll.

Levodopa (LD) is an effective treatment to control symptoms of Parkinson's disease (PD) and during the first few years of LD treatment patients are said to experience a 'honeymoon' period, reflective of a sustained beneficial response to this dopamine pro-drug. However, the response to LD changes over time and patients require higher and more frequent LD doses. Most patients develop motor response complications such as frequent periods of immobility and involuntary movements. The major unmet need is to preserve the initial, stable, response to LD and prevent the development of motor response complications. It is therefore essential to identify the underlying mechanism for the changes in LD effectiveness.

This study involves only 1 study visit. Prior to the study visit, participants will be asked to complete questionnaires and will receive an at-home stool collection kit. At the time of the study visit, participants will turn in their questionnaires and their at-home stool sample. On the day of the study visit, the patient will have fasted (overnight for 8 hours) and taken their last LD medication 12 hours prior to the visit. Each patient (and healthy control) will bring a home collected stool sample to their scheduled research visit which will be taken and stored in -80 freezers for the microbiota analysis. Oral swab will be collected for oral microbiota analysis. For PD patients only, an indwelling catheter for blood draws will be placed by one of the highly experienced GI infusion nurses and a fasting blood sample will be drawn. At the time of the visit, each patient will be given their morning LD dose (1.5 times their usual dose as they did not take LD for 12 hours), and then both patients and their controls will be given lactulose (20 mg) and have their breath collected every 10 minutes for the first hour, and then every 15 minutes for the following 3 hours (total 4 hours) for measurement of breath hydrogen and methane to assess mouth to cecum transit and presence/absence of small bowel bacteria overgrowth. PD patients will also have a blood sample drawn every 30 minutes, for 4 hours (total 8 draws) to measure LD and LD metabolites in the plasma Patients and controls will be provided a light breakfast (2 white wheat bread toasts with thin layer of butter and coffee). Each patient and control will complete a detailed dietary questionnaire (FFQ and 24 hour diet recall), a food timing questionnaire and screener and a structured demographic questionnaire. PD patients will also complete a questionnaire that includes PD-related information. Patients will also perform a simple finger tapping task to asses and quantify speed of movement before, during and after completion of study. Finger tapping task will be done using 2 mechanical counters mounted on a board. The patients go back and forth between these two counters and the number of taps in 30 seconds will be automatically recorded. In addition, patients will log their motor state (OFF versus ON) every half an hour on a PD diary.

FOR PATIENTS WITH PD:

Inclusion Criteria:

• Documented diagnosis of Parkinson's disease
• On Levodopa treatment

Exclusion Criteria:

• History of GI diseases [except for hemorrhoids or occasional (<3 times a week) heartburn] like Inflammatory bowel disease or Celiac disease
• Antibiotic use within last 12 weeks
• Use of probiotic supplement over the prior 2 weeks except yogurt
• Intentional change in diet
• Chronic use of NSAIDS. A washout period of 3 weeks is needed before the subject could be enrolled into the study. Low does aspirin is allowed.

FOR CONTROL GROUP:

Inclusion Criteria:

• No clinical evidence of neurological disorders including Parkinson's disease
• Live in the same household as the Parkinson's Disease patient or is a first degree relative of the PD patient.

Exclusion Criteria:

• History of GI diseases [except for hemorrhoids or occasional (<3 times a week) heartburn] like Inflammatory bowel disease or Celiac disease
• Antibiotic use within last 12 weeks
• Use of probiotic supplement over the prior 2 weeks except yogurt
• Intentional change in diet
• Chronic use of NSAIDS. A washout period of 3 weeks is needed before the subject could be enrolled into the study. Low does aspirin is allowed.

We plan to enroll two groups of established PD patients on a stable dose of LD for the prior 4 weeks. We will enroll twelve patients in each of the following two groups: Group 1:"low frequency dose" patients and Group 2:" high frequency dose "patients. Low frequency is defined as ≤ 3 LD doses a day and high frequency as ≥ 5 LD doses per day. Each PD patient will have a household healthy control/spouse enrolled into the study. Single patients with no spouse will still be eligible to enroll.