Supplementation with short-chain fatty acids and a prebiotic improves clinical outcome in Parkinson's disease: a randomized double-blind prospective study.

All intervention groups achieved clinically meaningful reductions in motor symptoms over 6 months of supplementation.

• 72 people with Parkinson's disease were enrolled in the randomized double-blind prospective study.
• Patients received propionic and butyric acid and/or the prebiotic fiber 2'-fucosyllactose over 6 months in combination with existing Parkinson's disease-specific therapy.
• Motor symptom improvements were described as 'robust' with 'clinically meaningful reductions' across all intervention groups.
• Neurological assessments were performed before as well as 3 and 6 months after supplementation.

Motor benefits from supplementation were paralleled by clinically relevant reductions in levodopa medication.

• Reductions in levodopa medication were observed alongside motor symptom improvements.
• The reductions were described as 'clinically relevant.'
• This was observed across the intervention groups receiving short-chain fatty acids and/or prebiotic supplementation.
• Levodopa dose changes were assessed in the context of patients continuing their existing Parkinson's disease-specific therapy.

Effects on nonmotor symptoms were more heterogeneous across intervention groups.

• In contrast to the consistent motor improvements, nonmotor symptom responses varied.
• The heterogeneity in nonmotor symptom effects was noted across the different intervention arms.
• Patients underwent complete neurological assessment including evaluation of nonmotor symptoms at baseline, 3 months, and 6 months.

The interventions modulated peripheral immune responses in Parkinson's disease patients.

• Peripheral immune responses were assessed from blood samples collected before and after supplementation.
• Multiobjective analysis revealed immune parameters associated with an optimal response to supplementation.
• Immune modulation was observed alongside clinical symptom improvements.
• The interventions involved short-chain fatty acids (propionic and butyric acid) known to promote immune regulation.

Supplementation enhanced mitochondrial respiration in immunocytes.

• Enhanced mitochondrial respiration was observed in immunocytes following the interventions.
• This finding was reported alongside peripheral immune response modulation.
• Blood samples were collected before as well as 3 and 6 months after supplementation for these analyses.

Postintervention microbiota remodeled inflammatory and barrier-related gene sets in gut organ cultures and improved in vitro barrier functions.

• Stool samples were collected before as well as 3 and 6 months after supplementation.
• Postintervention microbiota were used in gut organ culture experiments to assess transcriptional changes.
• Inflammatory and barrier-related gene sets were remodeled by postintervention microbiota.
• In vitro barrier function improvements were observed following the intervention.

Treatment response was associated with baseline microbiome composition, distinct patterns of colonic transcription, and permeability ex vivo.

• Microbiome composition prior to intervention was linked to treatment response outcomes.
• Distinct patterns of colonic transcription were associated with differential treatment responses.
• Colonic permeability measured ex vivo was also associated with treatment response.
• These associations suggest that baseline gut characteristics may predict responsiveness to SCFA/prebiotic supplementation in Parkinson's disease.

Parkinson's disease is associated with a dysbiotic, proinflammatory gut microbiome, disruptions to intestinal barrier functions, and immunological imbalance.

• This background context motivated the investigation of microbiota-targeted supplementation in Parkinson's disease.
• Microbiota-produced short-chain fatty acids such as propionic and butyric acid promote gut barrier integrity and immune regulation.
• The impact of short-chain fatty acids on Parkinson's disease pathology was described as 'mostly unknown' prior to this study.