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

BackgroundParkinsons 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. ObjectivesTo evaluate supplementation with short-chain fatty acids as an add-on intervention in PD. MethodsIn 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. ResultsWe 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. ConclusionShort-chain fatty acids ameliorate clinical symptoms in Parkinsons disease patients and modulate mitochondrial function and peripheral immunity.