High Dietary Antioxidant Intake is Associated with Changes in Gut Microbiome Composition and Predicted Metabolic Pathways in Parkinson’s Disease, but these Alterations were Not Associated with Shifts in Cognitive Performance

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by both motor and non-motor symptoms. In addition to the neuropathological and clinical features, increasing evidence suggests that the gut microbiome may contribute to PD pathophysiology through the gut-brain axis. Dietary antioxidants have gained increasing attention for their potential neuroprotective effects, which may be explained by their ability to modulate the gut microbiome and reduce oxidative stress. However, the relationship between antioxidant-driven microbiome changes and cognitive performance in PD remains poorly understood. This study investigated the effects of dietary antioxidants, including vitamins A, C, and E, alpha-carotene, beta-carotene, and their combined effects, on the gut microbiome and cognitive performance in PD patients. We analyzed 16S rRNA gene sequencing data from 197 fecal samples collected from PD patients, with cognitive performance assessed using the Montreal Cognitive Assessment (MoCA). Dietary antioxidant intake was standardized into Dietary Antioxidant Index, and PD patients were stratified into low, medium, and high intake tertiles accordingly. High antioxidant intake was associated with significant shifts in gut microbial community composition, as measured by beta diversity. Indicator species analysis identified Escherichia-Shigella as a biomarker of low beta-carotene and vitamin C intake groups, although its relative abundance was not significantly correlated with MoCA scores. Functional pathway analysis showed reduced abundance of predicted metabolic pathways in high beta-carotene and vitamin C intake groups, including pathways related to lipopolysaccharide biosynthesis, amino acid degradation, and oxidative stress detoxification. However, the microbiome composition of these significantly differentially abundant pathways was not associated with cognitive performance.