Supplementation with short-chain fatty acids and the prebiotic 2FL improves clinical outcome in PD

Background Parkinson’s disease (PD) is associated with dysbiosis, proinflammatory gut microbiome, disruptions to intestinal barrier functions, and immunological imbalance. Microbiota-produced short-chain fatty acids promote gut barrier integrity and immune regulation, but their impact on PD pathology remains mostly unknown. Objectives To evaluate supplementation with short-chain fatty acids as an add-on intervention in PD. Methods In a randomized double-blind prospective study, 72 PD patients received short-chain fatty acids and/or the prebiotic fiber 2′-fucosyllactose supplementation over 6 months. Results We observed improvement in motor and nonmotor symptoms, in addition to modulation of peripheral immunity and improved mitochondrial respiration in immunocytes. The supplementation had no effect on microbiome diversity or composition. Finally, multiobjective analysis and comprehensive immunophenotyping revealed parameters associated with an optimal response to short-chain fatty acids and/or 2′-fucosyllactose supplementation. Conclusion Short-chain fatty acids ameliorate clinical symptoms in Parkinson’s disease patients and modulate mitochondrial function and peripheral immunity. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial DRKS; registration number DRKS00027061 ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was performed from November 2019 to August 2020 after being approved by the Ethics Committee of the Ruhr-University Bochum (November 2019; registration number 19-6713). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All new datasets will be made freely available at the time of publication. Any additional information required to reanalyze the data reported in this work is available from the corresponding author upon request. This paper does not report any original code or algorithms. The code used in this study is freely available at https://www.ci.ovgu.de/Research/Codes.html and on GitHub.