Safety and feasibility of fecal microbiota transplantation for Parkinson’s disease patients: a protocol for a self-controlled interventional donor-FMT pilot study

Abstract

Several experimental studies suggest a role of the gut microbiota in the pathophysiology of Parkinson’s disease (PD) via the gut-brain axis. In addition, the gut microbiota can influence the metabolism of levodopa, which is the mainstay of treatment of PD. Therefore, modifying the gut microbiota by fecal microbiota transplantation (FMT) could be a supportive treatment strategy. We developed a study protocol for a single center, prospective, self-controlled, interventional, safety and feasibility donor-FMT pilot study with randomization and double blinded allocation of donor feces. The primary objectives are to assess feasibility and safety of FMT in PD patients. Secondary objectives are to explore whether FMT leads to alterations of motor complications and PD symptoms in the short term, determine alterations in gut microbiota composition and donor-recipient microbiota similarities and their association with PD symptoms and motor complications, assess the ease of the study protocol and examine FMT-related adverse events in PD patients. The study population will consist of 16 idiopathic PD patients that use levodopa and experience motor complications. They will receive FMT with feces from one of two selected healthy human donors. Patients will be pretreated with vancomycin and bowel lavage to increase donor feces engraftment, and domperidone to prevent nausea and regurgitation. The FMT will be performed via direct injection of the fecal suspension into the duodenum via a gastroscope. There will be six follow-up moments during three months. Blood will be drawn on three occasions. Physical examination, filling in of questionnaires and a diary, and collection of stool samples are performed at baseline and each in-person follow-up visit (except for the FMT visit). This study was approved by the Medical Ethical Committee Leiden Den Haag Delft (ref. P20.087) and is registered in the Netherlands Trial Register (NL9438). Study results will be disseminated through publication in peer-reviewed journals and international conferences.

Unveiling the Journey from the Gut to the Brain: Decoding Neurodegeneration–Gut Connection in Parkinson’s Disease

“…This method to restore eubiosis in patients is called FMT. FMT has a high success rate; however, it has some low-risk and transient side effects like abdominal discomfort, bloating, diarrhea, or constipation, and the risk of infection transmission from bacterial translocation; chances of bacterial infections are low but not completely avoidable. , The use of FMT in PD is still at the initial stage, but FMT has proven beneficial in some studies where FMT, when given through colonoscopy to PD patients, was found to relieve motor and nonmotor symptoms linked with the disease. − In one randomized, double-blind, placebo-controlled pilot study, when the lyophilized FMT product was orally administered to 12 subjects with mild to moderate PD and constipation, PD patients well tolerated the dose of FMT, which caused increased diversity in the intestinal microbiome and improvement in constipation, intestinal motility, and gut transit. Also, FMT improved motor and nonmotor symptoms in these cases .…”

Targeting the Gut–Brain Axis with Fecal Microbiota Transplantation: Considerations on a Potential Novel Treatment for Parkinson's Disease

“…Several preliminary clinical observations on FMT for different neurological disorders, 32 including PD, [33][34][35][36] are being published, and study protocols exploring this potential treatment for PD are being registered. 37 So far, a total of 33 PD cases have been reported, all studied in open-label fashion. [33][34][35][36] The reported patients presented with different clinical characteristics and were evaluated in different ways for variable follow-up periods.…”

“…Several preliminary clinical observations on FMT for different neurological disorders, 32 including PD, 33 , 34 , 35 , 36 are being published, and study protocols exploring this potential treatment for PD are being registered. 37 …”

Therapeutic Perspectives for Microbiota Transplantation in Digestive Diseases and Neoplasia—A Literature Review

“…Additionally, a recent review realized by Yuanyuan Zhao et al outlines the implications of the gut microbiota in developing liver diseases such as fatty liver disease, cirrhosis, and even implications in hepatocarcinoma. This review highlights the importance of FMT by assessing the gut–liver axis in recovering from these pathologies [ 4 , 12 , 13 , 14 , 15 ]. Since specialized studies have demonstrated a change in the intestinal microbiota in patients with rheumatoid arthritis, with the frequent presence of Bacteroides , Escherichia–Shigella , and Prevotella bacteria, at Chinese PLA General Hospital, FMT was successful in a 20-year-old patient with a 5-year history of rheumatoid arthritis [ 16 ].…”