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Randomized Controlled Trial
. 2024 Sep 1;81(9):925-938.
doi: 10.1001/jamaneurol.2024.2305.

Fecal Microbiota Transplantation for Treatment of Parkinson Disease: A Randomized Clinical Trial

Filip Scheperjans  1   2 , Reeta Levo  1 , Berta Bosch  3 , Mitja Lääperi  4 , Pedro A B Pereira  1 , Olli-Pekka Smolander  1 , Velma T E Aho  1 , Nora Vetkas  1   5 , Lotta Toivio  6 , Veera Kainulainen  1   3 , Tatyana D Fedorova  7 , Perttu Lahtinen  8 , Rebekka Ortiz  9 , Valtteri Kaasinen  10 , Reetta Satokari  3 , Perttu Arkkila  2   5
Affiliations
Randomized Controlled Trial

Fecal Microbiota Transplantation for Treatment of Parkinson Disease: A Randomized Clinical Trial

Filip Scheperjans et al. JAMA Neurol. .

Abstract

Importance: Dysbiosis has been robustly demonstrated in Parkinson disease (PD), and fecal microbiota transplantation (FMT) has shown promising effects in preclinical PD models.

Objective: To assess the safety and symptomatic efficacy of colonic single-dose anaerobically prepared FMT.

Design, setting, and participants: This was a double-blind, placebo-controlled, randomized clinical trial conducted between November 2020 and June 2023 with a follow-up period of 12 months at 4 hospitals in Finland. Patients with PD aged 35 to 75 years in Hoehn & Yahr stage 1-3 with a mild to moderate symptom burden and dysbiosis of fecal microbiota were included. Of 229 patients screened, 48 were randomized and 47 received the intervention. One patient discontinued due to worsening of PD symptoms. Two further patients were excluded before analysis and 45 were included in the intention-to-treat analysis.

Intervention: Participants were randomized in a 2:1 ratio to receive FMT or placebo via colonoscopy.

Main outcomes and measures: The primary end point was the change of Movement Disorder Society Unified Parkinson's Disease Rating Scale parts I-III (part III off medication) at 6 months. Safety was assessed by recording adverse events (AEs).

Results: The median (IQR) age was 65 (52.5-70.0) years in the placebo group and 66 (59.25-69.75) years in the FMT group; 9 (60.0%) and 16 (53.3%) patients were male in the placebo group and the FMT group, respectively. The primary outcome did not differ between the groups (0.97 points, 95% CI, -5.10 to 7.03, P = .75). Gastrointestinal AEs were more frequent in the FMT group (16 [53%] vs 1 [7%]; P = .003). Secondary outcomes and post hoc analyses showed stronger increase of dopaminergic medication and improvement of certain motor and nonmotor outcomes in the placebo group. Microbiota changes were more pronounced after FMT but differed by donor. Nevertheless, dysbiosis status was reversed more frequently in the placebo group.

Conclusions and relevance: FMT was safe but did not offer clinically meaningful improvements. Further studies-for example, through modified FMT approaches or bowel cleansing-are warranted regarding the specific impact of donor microbiota composition and dysbiosis conversion on motor and nonmotor outcomes as well as medication needs in PD.

Trial registration: ClinicalTrials.gov Identifier: NCT04854291.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Scheperjans reported grants from the Emil Aaltonen Foundation, Konung Gustav V:s och Drottning Victorias Stiftelse, the Olvi Foundation, the Yrjö Jahnsson Foundation, the Stockmann Foundation, the Sigrid Jusélius Foundation, the Research Council of Finland, and the Hospital District of Helsinki and Uusimaa during the conduct of the study as well as grants from Renishaw; personal fees from AbbVie, Axial Biotherapeutics, Orion, GE Healthcare, Merck, Teva, Bristol Myers Squibb, Sanofi, Biocodex, Lundbeck, Nordic Infucare, Adamant Health, and Biogen; and nonfinancial support from MRM Health and Novartis outside the submitted work. In addition, Dr Scheperjans had a patent for FI127671 issued, a patent for US10139408 issued, a patent for US11499971 issued, a patent for EP3149205 issued, and a patent for EP3789501 issued; is listed as inventor on the invention disclosure of the Parkinson disease dysbiosis test; and is founder of NeuroBiome Ltd. Dr Aho reported a patent for FI127671 issued, a patent for US10139408 issued, a patent for US11499971 issued, a patent for EP3149205 issued, a patent for EP3789501 pending, and a patent for US20230221314 pending. Dr Vetkas reported grants from the Orion Research Foundation, the Maire Taponen Foundation, the Päivikki and Sakari Sohlberg Foundation, and the Mary and George Ehrnrooth Foundation during the conduct of the study. Dr Fedorova reported grants from the Danish Parkinson Association outside the submitted work. Dr Ortiz reported grants from Emil Aaltonen foundation during the conduct of the study. Dr Kaasinen reported grants from the Finnish Alcohol Research Foundation, the Turku University Foundation, the Finnish Cultural Foundation, Turku University Hospital (state research funding) and personal fees from AbbVie Finland, Nordic Infucare AB, Adamant Health, and Orion Pharma outside the submitted work. Dr Satokari reported grants from the Sigrid Juselius Foundation (payment to University of Helsinki), the Research Council of Finland (payment to University of Helsinki), and the Päivikki and Sakari Sohlberg Foundation (payment to University of Helsinki) and other from the Finnish National Agency for Education (research scholarship; payment to University of Helsinki) during the conduct of the study as well as other from the Paulo Foundation (research scholarship; personal grant) and grants from the European Health and Digital Executive Agency Research project Endotarget (payment to the University of Helsinki), the European Health and Digital Executive Agency Research project Long-COVID (payment to the University of Helsinki), and the Cancer Foundation (payment to the University of Helsinki) outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Trial Profile
DBS indicates deep brain stimulation; FMT, fecal microbiota transplantation; MoCA, Montreal Cognitive Assessment; NSAID, nonsteroidal anti-inflammatory drugs; PD, Parkinson disease.
Figure 2.
Figure 2.. Results for the Primary and Selected Secondary Outcomes
BAI indicates Beck Anxiety Inventory; FMT, fecal microbiota transplantation; LEDD, levodopa-equivalent daily dose; MDS-UPDRS, Movement Disorder Society Unified Parkinson’s Disease Rating Scale; MoCA, Montreal Cognitive Assessment; NMSS, Non-Motor Symptoms Scale; TUG, timed up and go. aDifference between FMT and placebo groups: P < .01. bDifference between FMT and placebo groups: P < .05.
Figure 3.
Figure 3.. Results for Gut-Related Secondary Outcomes
CBM indicates complete bowel movements; FMT, fecal microbiota transplantation; IBS-SSS, Irritable Bowel Severity Scoring System; SCBM, spontaneous complete bowel movements. aDifference between FMT and placebo groups: P < .01. bDifference between FMT and placebo groups: P < .05. cDifference between FMT and placebo groups: P < .001.
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References

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