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

Herbert L DuPont; Jessika Suescun; Zhi-Dong Jiang; Eric L Brown; Heather T Essigmann; Ashley S Alexander; Andrew W DuPont; Tehseen Iqbal; Netanya S Utay; Michael Newmark; Mya C Schiess

doi:10.3389/fneur.2023.1104759

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

Front Neurol. 2023 Mar 2:14:1104759. doi: 10.3389/fneur.2023.1104759. eCollection 2023.

Authors

Herbert L DuPont^{1

2

3

4}, Jessika Suescun⁵, Zhi-Dong Jiang², Eric L Brown², Heather T Essigmann², Ashley S Alexander¹, Andrew W DuPont³, Tehseen Iqbal², Netanya S Utay⁶, Michael Newmark^{1

4}, Mya C Schiess⁵

Affiliations

¹ Microbiome Research Center, Kelsey Research Foundation, Houston, TX, United States.
² Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, TX, United States.
³ Department of Internal Medicine, University of Texas McGovern Medical School, Houston, TX, United States.
⁴ Medical Services and Specialties, Kelsey Seybold Clinic, Houston, TX, United States.
⁵ Department of Neurology, University of Texas McGovern Medical School, Houston, TX, United States.
⁶ Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States.

Abstract

Background and purpose: The 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.

Methods: This 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).

Results: Fecal 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.

Conclusions: Subjects 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 registration: ClinicalTrial.gov, identifier: NCT03671785.

Keywords: Parkinson's disease; constipation; dysbiosis; fecal microbiota transplantation; microbiome.

Associated data

ClinicalTrials.gov/NCT03671785

Grants and funding

This study was funded by the MD Anderson Foundation, the Joe & Jessie Crump Foundation Medical Research Fund and the Kelsey Research Foundation (HD and AA), and the University of Texas School of Public Health (HD and Z-DJ). This study was also supported by the Texas Medical Center, Digestive Diseases Center [Public Health Service grant DK56338 (HD)].