Abstract
Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder that poses a substantial threat to global human health. Yam (Dioscorea opposita Thunb.) is a traditional medicinal and edible plant that has long been used in Asia, Africa, and the Caribbean. Its major bioactive components, such as dioscin and polysaccharides, have been reported to exhibit neuroprotective effects; however, the impact of dietary yam on PD progression remains to be elucidated. Therefore, we sought to evaluate its neuroprotective potential and the underlying mechanisms in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-induced PD mice. Methods: Mice received six-week dietary yam supplementation. Behavioral, histological, and neurochemical analyses were performed to assess motor function, dopaminergic neuron integrity, and dopamine levels. Gut microbiota and metabolic profiles were analyzed using 16S rRNA gene sequencing and non-targeted metabolomics. Transcriptomic sequencing and Western blot analysis of the substantia nigra pars compacta (SNc) were conducted to investigate molecular mechanisms, and integrative multi-omics analysis was applied to explore microbiota–metabolite–host interactions. Results: Yam supplementation improved motor function, preserved nigrostriatal dopaminergic neurons, and restored striatal dopamine levels in PD mice. Notably, yam was associated with the maintenance of intestinal homeostasis by strengthening barrier integrity and enriching beneficial taxa, including Ileibacterium, Lachnospiraceae NK4A136 group, and Blautia. Consistently, yam also elevated neuroprotective purines and amino acids, including inosine, xanthine, and succinic acid. At the molecular level, yam treatment modulated mitochondrial oxidative phosphorylation by increasing PGC-1α and COX7c expression, and reduced inflammasome-related neuroinflammatory signaling. Integrative modeling showed significant associations between yam-modulated genes and PD-related indices with microbiota and metabolites. Conclusions: These findings suggest that yam may represent a potential dietary strategy for alleviating PD-related neurodegeneration by modulating the microbiota–gut–brain axis.