Dietary Yam Ameliorates Parkinson’s Disease in Mice via Gut Microbiota-Driven Mitochondrial Improvement and Neuroinflammation Inhibition

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that poses a substantial threat to global human health. There has been a growing focus on the crucial role of microbiota-gut-brain axis in the development and pathogenesis of PD, highlighting the potential benefits of microbiome-based dietary approaches. Yam (Dioscorea opposita Thunb.), a time-honored medicinal and edible plant revered in traditional Chinese medicine for its capacity to tonify the spleen, stomach, and kidneys. While its major bioactive components, such as dioscin and polysaccharides, exhibit neuroprotective effects, the impact of dietary yam on PD progression remains to be elucidated. Therefore, we sought to evaluate its neuroprotective potential and uncover the underlying mechanisms in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-induced PD mice. Six-week yam supplementation markedly improved motor function, preserved nigrostriatal dopaminergic neurons, and restored striatal dopamine levels in PD mice. Notably, yam maintained intestinal homeostasis by strengthening barrier integrity and enriching beneficial taxa such as Ileibacterium, Lachnospiraceae NK4A136 group, and Blautia. Concurrently, metabolomic analysis of colonic contents demonstrated that yam alleviated metabolic dyshomeostasis, specifically elevating a cluster of neuroprotective purines and amino acids, including inosine, xanthine, and succinic acid. Mechanistically, yam enhanced mitochondrial oxidative phosphorylation via restoring the PGC1α and COX7c expression while suppressing NLRP3 inflammasome-mediated neuroinflammation. Integrating multi-omics analysis depicted a coordinated microbiome-metabolite-host interaction network, indicating that the neuroprotective mechanism of yam on PD might be related to the aforementioned improvement of microbiota-gut-brain axis. These findings demonstrate that yam serves as a promising medicinal and edible plant intervention for alleviating PD-related neurodegeneration by modulating the microbiota-gut-brain axis.