Microbiome characterization and reversal of dysbiosis in Parkinson’s disease by Fecal Microbiota Transplantation (1825)

Objective: To characterize the intestinal microbiome of patients with Parkinson’s disease (PD) and to reverse dysbiosis in PD by using Fecal Microbiota Transplantation (FMT) in a Phase 1/2a randomized controlled trial (RCT). Background: Gastrointestinal dysfunction, specifically constipation, is seen in a majority (70%) of patients with PD. Abnormal microbiome with reduced diversity of microbiota (dysbiosis) influences the neuroinflammatory process and mucosal permeability. It is hypothesized to facilitate mobilization of a-synuclein via the vagus nerve to the brain and alter the metabolism of dopaminergic drugs. Our group has extensively tested lyophilized orally delivered FMT for reversal of dysbiosis in patients with recurrent Clostridium difficile infection. Design/Methods: Initially, we collected fecal samples from 100 subjects with PD, characterized the microbiome using both 16S rRNA and whole-genome sequencing, and correlated this with motor and non-motor symptoms and gastrointestinal function. Subsequently, we launched a Phase 1/2a RCT using FMT to reverse dysbiosis in 12 early to moderate stage iPD patients. Subjects were randomly assigned to receive either FMT product in orally administered enteric-coated capsules (8 subjects) or matching placebo capsules (4 subjects) for 12 weeks. Patients are followed for 9 months, and during this time they will provide stool samples for microbiome analysis, serum for peripheral cytokines and chemokine analysis, undergo neurologic examinations (UPDRS, H&Y, MOCA, UPSIT) and complete questionnaires (PDQ-39, PAS, GDS, and PDNMS). Additionally, a SmartPill capsule is used before and after treatment to measure gut transit and intestinal pH. Results: Preliminary evaluation of microbiota shows an abnormal b-diversity with increased proportions of Rikenellaceae, Akkermansiaceae, and Enterobacteriaceae, with under-representation of Clostridiaceae. Conclusions: We will finish enrollment of our Phase1/2a RCT by the end of December 2019 and complete microbiome characterization. Disclosure: Dr. DuPont has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Aries Pharmaceutical. Dr. DuPont has received research support from Rebiotix. Dr. Suescun has nothing to disclose. Dr. Jiang has nothing to disclose. Dr. Brown has nothing to disclose. Dr. Iqbal has nothing to disclose. Dr. Alexander has nothing to disclose. Dr. DuPont has received research support from Vanda Pharmaceuticals Inc., Janssen, Allergan, and Shire.Dr. Newmark has nothing to disclose. Dr. Essigmann has nothing to disclose. Dr. Schiess has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Medtronic. Dr. Schiess has received research support from Medtronic.