TY  - JOUR
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
TI  - Supplementation with short-chain fatty acids and a prebiotic improves clinical outcome in Parkinson's disease: a randomized double-blind prospective study.
JO  - Scientific reports
VL  - 16
IS  - 1
SN  - 2045-2322
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2026-00038
SP  - 315
PY  - 2025
AB  - 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.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.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.Short-chain fatty acids ameliorate clinical symptoms in Parkinson's disease patients and modulate intestinal and peripheral immunity.This clinical trial was retrospectively registered with the German Clinical Trials Register (DRKS), registration number DRKS00027061 on 11/19/2021.
KW  - Humans
KW  - Parkinson Disease: microbiology
KW  - Parkinson Disease: diet therapy
KW  - Parkinson Disease: drug therapy
KW  - Prebiotics: administration & dosage
KW  - Male
KW  - Double-Blind Method
KW  - Female
KW  - Fatty Acids, Volatile: administration & dosage
KW  - Gastrointestinal Microbiome: drug effects
KW  - Aged
KW  - Middle Aged
KW  - Dietary Supplements
KW  - Prospective Studies
KW  - Treatment Outcome
KW  - Clinical improvement (Other)
KW  - Gut microbiome (Other)
KW  - Immunomodulation (Other)
KW  - Neurodegeneration (Other)
KW  - Neuroinflammation (Other)
KW  - Parkinson’s disease (Other)
KW  - Short chain fatty acids (Other)
KW  - Prebiotics (NLM Chemicals)
KW  - Fatty Acids, Volatile (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41350593
C2  - pmc:PMC12770440
DO  - DOI:10.1038/s41598-025-29692-x
UR  - https://pub.dzne.de/record/283142
ER  -