Characterization of blood metabolomic responses to deep brain stimulation in patients with Parkinson’s disease

Deep brain stimulation (DBS) constitutes one of the few therapeutic strategies for advanced Parkinson’s disease. Although DBS causes rapid alterations in neuronal metabolism, whether it remodels the circulating metabolome and thereby alleviates systemic symptoms remains unknown. Here, we used high-performance liquid chromatography–mass spectrometry to perform untargeted plasma metabolomics of plasma samples from patients with Parkinson’s disease pre- and post-DBS to profile transient metabolic alterations in plasma that could be attributed to DBS. Numerous metabolites involved in tyrosine metabolism—including dopamine, phenylacetaldehyde, 4-hydroxybenzaldehyde, and tyrosine—were reduced in abundance following DBS. In contrast, metabolites such as lactate were increased in abundance in response to DBS. We further characterized metabolites associated with the immediate therapeutic effects of DBS and identified acrylic acid level as a potential metabolic predictor of long-term prognosis. Collectively, our findings provide important insights into DBS-induced reprogramming of the plasma metabolome.