Supplementation with short-chain fatty acids and a prebiotic improves clinical outcome in Parkinson's disease: A randomized double-blind prospective study [RNA-Seq]
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 improvement in motor and nonmotor symptoms, in addition to modulation of peripheral immunity and improved 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. Overall design: Colon organ cultures were infused with microbiota samples collected from PD patients at baseline and 6 months postintervention (n=8, all intervention groups included) or with sterile medium as an internal control.