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Fecal microbiota transplantation in Parkinson's disease—A randomized repeat-dose, placebo-controlled clinical pilot study
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 mi...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019775/ https://www.ncbi.nlm.nih.gov/pubmed/36937520 http://dx.doi.org/10.3389/fneur.2023.1104759 |
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author | DuPont, Herbert L. Suescun, Jessika Jiang, Zhi-Dong Brown, Eric L. Essigmann, Heather T. Alexander, Ashley S. DuPont, Andrew W. Iqbal, Tehseen Utay, Netanya S. Newmark, Michael Schiess, Mya C. |
author_facet | DuPont, Herbert L. Suescun, Jessika Jiang, Zhi-Dong Brown, Eric L. Essigmann, Heather T. Alexander, Ashley S. DuPont, Andrew W. Iqbal, Tehseen Utay, Netanya S. Newmark, Michael Schiess, Mya C. |
author_sort | DuPont, Herbert L. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10019775 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100197752023-03-17 Fecal microbiota transplantation in Parkinson's disease—A randomized repeat-dose, placebo-controlled clinical pilot study DuPont, Herbert L. Suescun, Jessika Jiang, Zhi-Dong Brown, Eric L. Essigmann, Heather T. Alexander, Ashley S. DuPont, Andrew W. Iqbal, Tehseen Utay, Netanya S. Newmark, Michael Schiess, Mya C. Front Neurol Neurology 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. Frontiers Media S.A. 2023-03-02 /pmc/articles/PMC10019775/ /pubmed/36937520 http://dx.doi.org/10.3389/fneur.2023.1104759 Text en Copyright © 2023 DuPont, Suescun, Jiang, Brown, Essigmann, Alexander, DuPont, Iqbal, Utay, Newmark and Schiess. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neurology DuPont, Herbert L. Suescun, Jessika Jiang, Zhi-Dong Brown, Eric L. Essigmann, Heather T. Alexander, Ashley S. DuPont, Andrew W. Iqbal, Tehseen Utay, Netanya S. Newmark, Michael Schiess, Mya C. Fecal microbiota transplantation in Parkinson's disease—A randomized repeat-dose, placebo-controlled clinical pilot study |
title | Fecal microbiota transplantation in Parkinson's disease—A randomized repeat-dose, placebo-controlled clinical pilot study |
title_full | Fecal microbiota transplantation in Parkinson's disease—A randomized repeat-dose, placebo-controlled clinical pilot study |
title_fullStr | Fecal microbiota transplantation in Parkinson's disease—A randomized repeat-dose, placebo-controlled clinical pilot study |
title_full_unstemmed | Fecal microbiota transplantation in Parkinson's disease—A randomized repeat-dose, placebo-controlled clinical pilot study |
title_short | Fecal microbiota transplantation in Parkinson's disease—A randomized repeat-dose, placebo-controlled clinical pilot study |
title_sort | fecal microbiota transplantation in parkinson's disease—a randomized repeat-dose, placebo-controlled clinical pilot study |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019775/ https://www.ncbi.nlm.nih.gov/pubmed/36937520 http://dx.doi.org/10.3389/fneur.2023.1104759 |
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