TY - JOUR
T1 - Supplementation with short-chain fatty acids and a prebiotic improves clinical outcome in Parkinson’s disease
T2 - a randomized double-blind prospective study
AU - Hegelmaier, Tobias
AU - Duscha, Alexander
AU - Desel, Christiane
AU - Fuchs, Sabrina
AU - Shapira, Michal
AU - Amidror, Sivan
AU - Shan, Qihao
AU - Stangl, Gabriele I.
AU - Hirche, Frank
AU - Kempa, Stefan
AU - Maifeld, András
AU - Würtele, Lisa Marie
AU - Peplinski, Jana
AU - Jauk, Diana
AU - Naim, Gitali
AU - Shidlovsky, Nuphar
AU - Cohen, Adva
AU - Bennet, Yifat
AU - Paschold, Lisa
AU - Dumitru, Claudia A.
AU - Obermüller-Jevic, Ute
AU - Hustvedt, Svein Olaf
AU - Timmesfeld, Nina
AU - Gold, Ralf
AU - Zapf, Antonia
AU - Binder, Mascha
AU - Sandalcioglu, Ibrahim E.
AU - Mostaghim, Sanaz
AU - Przuntek, Horst
AU - Segal, Eran
AU - Yissachar, Nissan
AU - Haghikia, Aiden
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12/5
Y1 - 2025/12/5
N2 - 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. Registration: This clinical trial was retrospectively registered with the German Clinical Trials Register (DRKS), registration number DRKS00027061 on 11/19/2021.
AB - 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. Registration: This clinical trial was retrospectively registered with the German Clinical Trials Register (DRKS), registration number DRKS00027061 on 11/19/2021.
KW - Clinical improvement
KW - Gut microbiome
KW - Immunomodulation
KW - Neurodegeneration
KW - Neuroinflammation
KW - Parkinson’s disease
KW - Short chain fatty acids
UR - https://www.scopus.com/pages/publications/105026710209
U2 - 10.1038/s41598-025-29692-x
DO - 10.1038/s41598-025-29692-x
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C2 - 41350593
AN - SCOPUS:105026710209
SN - 2045-2322
VL - 16
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 315
ER -