Sleep disturbances are among the most prevalent non-motor symptoms of Parkinson's disease (PD), yet their underlying mechanisms remain inadequately understood. Emerging evidence has emphasized a strong association between gut health and sleep stability, with notable early alterations in microbial composition and short-chain fatty acid (SCFA) levels observed during the progression of PD. Consequently, targeting the gut as a therapeutic strategy for sleep disturbances in PD has become a focus of our research. In this study, we demonstrated that a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model exhibited a marked reduction in daytime sleep alongside an increase in nighttime sleep. Microbial sequencing and SCFA profiling revealed a significant decline in butyrate levels and the abundance of butyrate-producing bacteria. Correlation analysis indicated a significant positive correlation between butyrate levels and the duration of daytime non-rapid eye movement (NREM) sleep. Furthermore, supplementation with butyrate effectively restored normal sleep architecture in MPTP-induced PD mice. Further mechanistic studies revealed that this effect is mediated through the BDNF-TrkB pathway. These findings suggest that direct or indirect supplementation with butyrate may be a potential therapeutic approach for improving sleep disorders in PD patients.
© 2025. The Author(s).