Fecal microbiota transplantation in Parkinson's disease—A randomized repeat-dose, placebo-controlled clinical pilot study

Abstract

Background and purposeThe intestinal microbiome plays a primary role in the pathogenesis of neurodegenerative disorders and may provide an opportunity for disease modification. We performed a pilot clinical study looking at the safety of fecal microbiota transplantation (FMT), its effect on the microbiome, and improvement of symptoms in Parkinson's disease.MethodsThis was a randomized, double-blind placebo-controlled pilot study, wherein orally administered lyophilized FMT product or matching placebo was given to 12 subjects with mild to moderate Parkinson's disease with constipation twice weekly for 12 weeks. Subjects were followed for safety and clinical improvement for 9 additional months (total study duration 12 months).ResultsFecal microbiota transplantation caused non-severe transient upper gastrointestinal symptoms. One subject receiving FMT was diagnosed with unrelated metastatic cancer and was removed from the trial. Beta diversity (taxa) of the microbiome, was similar comparing placebo and FMT groups at baseline, however, for subjects randomized to FMT, it increased significantly at 6 weeks (p = 0.008) and 13 weeks (p = 0.0008). After treatment with FMT, proportions of selective families within the phylum Firmicutes increased significantly, while proportion of microbiota belonging to Proteobacteria were significantly reduced. Objective motor findings showed only temporary improvement while subjective symptom improvements were reported compared to baseline in the group receiving FMT. Constipation, gut transient times (NS), and gut motility index (p = 0.0374) were improved in the FMT group.ConclusionsSubjects with Parkinson's disease tolerated multi-dose-FMT, and experienced increased diversity of the intestinal microbiome that was associated with reduction in constipation and improved gut transit and intestinal motility. Fecal microbiota transplantation administration improved subjective motor and non-motor symptoms.Clinical trial registrationClinicalTrial.gov, identifier: NCT03671785.

Microbiome-based biomarkers to guide personalized microbiome-based therapies for Parkinson’s disease

“…The value of the biomarker in this case is to avoid supplementation that is counter indicated. FMT is showing promise for PD 28 , but it carries risks concerning safety and compatibility of donor sample with host environment. Using biomarkers, unnecessary FMT can be avoided, sparing the patients who do not have a dysbiotic microbiome and those whose only problem is low fiber-degraders.…”

Therapies for Parkinson’s disease and the gut microbiome: evidence for bidirectional connection

“…FMT has been shown to be beneficial in patients with Clostridium difficile infections and irritable bowel syndrome (IBS) where there is dysbiosis ( Barichella et al, 2016 ). Presently, there are multiple ongoing clinical trials investigating the effects of FMT on PD symptoms including constipation, motor symptoms, and restoration of gut homeostasis ( Xue et al, 2020 ; Kuai et al, 2021 ; Metta et al, 2021 ; Segal et al, 2021 ; DuPont et al, 2023 ), NCT03808389, NCT04854291, NCT05204641, NCT03671785 and it is possible that utilization of FMT in combination with DATs could improve PD progression and symptomology.…”

Gut Microbial Metabolome and Dysbiosis in Neurodegenerative Diseases: Psychobiotics and Fecal Microbiota Transplantation as a Therapeutic Approach—A Comprehensive Narrative Review

“…Recently, a double-blind, placebo-controlled pilot study, using orally administered, lyophilized FMT twice weekly for 12 weeks, reported improvements in subjective motor and non-motor symptoms, gut transit, intestinal motility, and constipation in PD patients. Moreover, proportions of selective families within the phylum Firmicutes significantly increased after FMT, while the proportion of Proteobacteria was significantly reduced [329].…”