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Abstract Objective The aim of this research is to delve into the preventive and therapeutic effects of Wu Mei Pill (WMP) on Parkinson's disease (PD), with a special emphasis on its capability to counteract the PD-induced imbalance in gut microbiota and unveil its underlying mechanisms. Methods In this investigation, a PD mouse model induced by 6-OHDA was employed to study the impact of WMP. Following the establishment of the PD model, a range of evaluations including behavioral assessments, immunohistochemistry, Western Blot (WB), and enzyme-linked immunosorbent assay (ELISA) were executed to assess neurological functions and the influence of WMP on PD. Fecal samples and brain tissues were analyzed for microbiome and transcriptome studies. Results Administration of WMP improved neurological function, elevated the number of TH + cells, and enhanced the dopamine levels in the brain. The damage to dopaminergic neurons induced by 6-OHDA was associated with an upsurge in pro-inflammatory bacteria (Bacteroides), and bacteria involved in tryptophan metabolism (Azospirillum_sp.47_25 and unclassified_Bacteroidia) and cholesterol metabolism (unclassified[Eubacterium]_coprostanoligenes_group), along with a reduction in anti-inflammatory bacteria (Roseburia). WMP addressed these microbial shifts and key metabolite alterations (L-Tryptophan and Bambuterol) in the brain. Conclusion The alterations in the microbiome triggered by damage to dopaminergic neurons have the potential to aggravate PD symptoms. WMP was able to correct significant microbial and metabolic disturbances in the brain, thus reducing the loss of dopaminergic neurons, boosting dopamine levels, and enhancing neurological functions.
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