Prebiotics in the Parkinson's Disease Microbiome
Prebiotics in the Parkinson's Disease Microbiome
There are about one million Parkinson's disease (PD) patients in America. The risks
 associated with whether or not an individual may develop PD include environment and genetic
 (biologic, hereditary) factors. Studies have show that certain things may be triggers, for
 example cells in the brain that are made active and associated inflammation in the brain. The
 gut is the largest interface between the PD patient and the environment, and it is highly
 thought to be pathway to the environment trigger. Research studies have looked at how
 information is passed back and forth between the brain and the gut.

 The goal of this study (pilot) is to gather information to conduct a larger clinical trial.
 For this pilot study is to determine if a microbiota-directed (bacteria in the gut)
 intervention (dietary bar) is capable of correcting the bacteria gut balance in PD. This is
 based on the thought that an imbalance of bacteria in the gut of PD patients may lead to the
 gut and intestines working correctly. The long term goal is to see if the intervention has
 the potential to modify the disease or protect the brain in PD. If the intervention
 successfully improves the bacterial imbalance in PD, it will be the first attempt to modify
 the Gut-Brain communication in PD, which can lead to additional studies aimed at improving
 the disease progression or prevention.

 In this project, the investigators will test how well Parkinson's disease patients tolerate
 changes in the gut and intestines by providing the participants a dietary bar to eat for 10
 days. The investigators intend to conduct this pilot clinical trial in which the
 investigators believe that daily oral intake of a "prebiotic" mixture will be safe and well
 tolerated in a small number Parkinson's disease participants prior to a larger clinical trial
 looking at efficacy.
Intestinal microbiota, are a dynamic community of commensal bacteria that modulate gut
 homeostasis and systemic biological processes including brain development and function
 through a bidirectional "Gut-Brain axis". Recent studies in both rodent models of disease and
 human have shown disrupted intestinal microbiota community in multiple systemic metabolic and
 inflammatory disorders including neurological disease. More specifically emerging evidence
 shows that stool and intestinal mucosal associated microbiota composition and function are
 abnormal in PD patients. Divergence of commensal bacteria composition from the microbial
 communities found in healthy persons (so called "dysbiosis"), has been associated with PD in
 early and late stages, as well as in patients with REM sleep behavior disorder (RBD), a group
 that are at high risk of progression to PD.

 In this project, the investigators will test the tolerability of Parkinson's disease patients
 in modulating the gut microbiota through dietary means. The investigators intend to conduct a
 pilot clinical trial in which the investigators hypothesize that daily oral intake of a
 prebiotic mixture will be safe and well tolerated in a small number Parkinson's disease
 participants prior to a larger clinical trial looking at efficacy.

 Research design and protocol:

 The study is an open-label, non-randomized study in 10 Parkinson's disease participants at
 Rush University Medical Center (RUMC) under the supervision of Drs. Hall and Keshavarzian.
 The trial will include 10 PD patients who are de novo (not yet on medication) or moderate
 stage (on medications). Participants will take the prebiotics in a form of a bar (Table 1)
 for 10 days- one bar (10 gram fiber) a day for 3 days and then one bar twice a day for
 additional one week.

 Each participant will have a baseline visit and a follow up visit after 10 days of the
 intervention (consumption of prebiotic dietary bar). At each visit, participants will
 complete questionnaires regarding adverse events including a questionnaire that rates bowel
 movement, stool consistency, discomfort, flatulence, abdominal pain, and bloating on a scale
 from 1 (best) to 10 (worst). Participants will also complete a Perceived Stress Questionnaire
 (Appendix D) and GI Symptom and Severity Checklist (Appendix A). Participants will be asked
 to fill out a diet record (24ASA diet questionnaire) (Appendix E) during the last 3 days on
 the intervention. Participant will also are asked to self-collect stool at home before
 consuming (eating) the first probiotic bar in the study and during the last day of the study
 at home. Supplies for stool collection (2 stool collection kit) and instructions for specimen
 handling and for completing these tasks will be given at Visit 1 and refreshed before visit
 2. At visit 1 participants will be provided with 2 stool collection kits. First stool will be
 collected at home about 1 day and participants are asked to mail the stool in a pre-paid Fed
 Ex right after collecting the stool. The second stool collection will be on the last day that
 participants consume the probiotic bars prior to coming to for study visit 2 when the
 participants bring the stool to the study visit. The kit includes supplies to preserve the
 sample with gas packs and collection bag so the sample can be brought with the participant to
 the visits within 24 hours. The self-collected stool samples will be saved by the study team
 and frozen for future use. Participants will be asked to complete several dietary
 questionnaires including a Mediterranean diet screener (Appendix F), food timing screener
 (Appendix B) and food frequency questionnaire (Appendix C). Before Visit 2, each participant
 will collect the stool and complete the 3-day food record; these will be returned at Visit 2.
 At Visit 2, participants will complete a Perceived Stress Questionnaire (Appendix D) and GI
 Symptom and Severity Checklist and associated instructions (Appendix A). Each participant
 will also have blood draw (1 red top to collect serum and 1 EDTA tube to collect plasma) at
 visit 1 (baseline) and at visit 2 (completion of the study) to check for serum short chain
 fatty acids, lipopolysaccharides, interleukins and cytosine monophosphate(check for safety).

 Participants will provide written informed consent (Visit 1) before any study procedures,
 data or sample collection are performed.
Inclusion Criteria:

 -  Clinical diagnosis of Parkinson's disease,

 -  >age 30,

 -  Must be able to consent

 Exclusion Criteria:

 -  prior intestinal resection,

 -  patient history of GI diseases except for hiatal hernia, gastroesophageal reflux
 disease, hemorrhoids,

 -  severe renal disease defined by creatinine more than 2 ½ times normal,

 -  markedly abnormal liver function defined by liver function tests over 4 times normal
 levels or elevated bilirubin,

 -  antibiotic use within the last 12 weeks prior to enrollment,

 -  a plan to have a major change in dietary habit during the study,

 -  consumption of probiotics, prebiotics or synbiotics without an appropriate 2 week
 washout period