Item

Supplementation with short-chain fatty acids and a prebiotic improves clinical outcome in Parkinson’s disease: a randomized double-blind prospective study

Hegelmaier, Tobias
; 
Duscha, Alexander
; 
Desel, Christiane
; 
Fuchs, Sabrina
; 
Shapira, Michal
; 
Amidror, Sivan
; 
Shan, Qihao
; 
Stangl, Gabriele I.
; 
Hirche, Frank
; 
Kempa, Stefan
... show 10 more
Author
Hegelmaier, Tobias
Duscha, Alexander
Desel, Christiane
Fuchs, Sabrina
Shapira, Michal
Amidror, Sivan
Shan, Qihao
Stangl, Gabriele I.
Hirche, Frank
Kempa, Stefan
Maifeld, András
Würtele, Lisa-Marie
Peplinski, Jana
Jauk, Diana
Naim, Gitali
Shidlovsky, Nuphar
Cohen, Adva
Bennet, Yifat
Paschold, Lisa
Dumitru, Claudia A.
Obermüller-Jevic, Ute
Hustvedt, Svein-Olaf
Timmesfeld, Nina
Gold, Ralf
Zapf, Antonia
Binder, Mascha
Sandalcioglu, Ibrahim E.
Mostaghim, Sanaz
Przuntek, Horst
Segal, Eran
Yissachar, Nissan
Haghikia, Aiden
Supervisor
Department
Computational Biology
Embargo End Date
Type
Journal article
Date
2025
License
Language
English
Collections
Publications
Show all metadata
Research Projects
Organizational Units
Journal Issue
Abstract
Background Parkinson’s disease is associated with a dysbiotic, proinflammatory gut microbiome, disruptions to intestinal barrier functions, and immunological imbalance. Microbiota-produced short-chain fatty acids, such as propionic and butyric acid promote gut barrier integrity and immune regulation, but their impact on Parkinson’s disease pathology remains mostly unknown. Methods In a randomized double-blind prospective study, 72 people with Parkinson’s disease received propionic and butyric acid and/or the prebiotic fiber 2′-fucosyllactose supplementation over 6 months in combination with existing Parkinson’s disease-specific therapy. Patients underwent complete neurological assessment and provided blood and stool samples before as well as 3 and 6 months after supplementation. Results We observed a robust improvement in motor symptoms, with all intervention groups achieving clinically meaningful reductions. These motor benefits were paralleled by clinically relevant reductions in levodopa medication. In contrast, effects on nonmotor symptoms were more heterogeneous. Notably, the interventions also modulated peripheral immune responses and enhanced mitochondrial respiration in immunocytes. Postintervention microbiota remodeled inflammatory and barrier-related gene sets in gut organ cultures and improved in vitro barrier functions. Treatment response was associated with microbiome composition, distinct patterns of colonic transcription and permeability ex vivo. Multiobjective analysis revealed immune parameters associated with an optimal response to supplementation. Conclusion Short-chain fatty acids ameliorate clinical symptoms in Parkinson’s disease patients and modulate intestinal and peripheral immunity.
Citation
T. Hegelmaier et al., “Supplementation with short-chain fatty acids and a prebiotic improves clinical outcome in Parkinson’s disease: a randomized double-blind prospective study.,” Sci Rep, Dec. 2025, doi: 10.1038/S41598-025-29692-X
Source
Scientific Reports
Conference
Keywords
Parkinson’s Disease, Gut Microbiome, Immunomodulation, Short-Chain Fatty Acids, Clinical Improvement, Neurodegeneration, Neuroinflammation
Subjects
Source
Publisher
Springer Nature
DOI
10.1038/s41598-025-29692-x
Additional links
https://www.nature.com/articles/s41598-025-29692-x
Full-text link