Pain is a common non-motor symptom of Parkinson's disease (PD) that significantly impacts patients' quality of life. Recently, the role of the gut-brain axis in the pathogenesis of PD has garnered considerable attention. However, the relationship between gut microbiota-induced changes in plasma metabolites and PD-associated pain remains poorly understood. To address this, we analyzed 64 PD patients with pain (PDP), 36 non-PD individuals with pain (nPDP), and 50 healthy controls (HC). Using 16S rDNA gene sequencing and ultra-high-performance liquid chromatography-tandem mass spectrometry (LC-MS), we characterized and compared the gut microbiota and plasma metabolite profiles across these groups. Additionally, correlation analyses were conducted to identify meaningful associations between microbial and metabolite data. Our findings revealed significant differences among the PDP, nPDP, and HC groups, particularly in taxa such as Bacteroidales, Gammaproteobacteria, and Faecalibacterium prausnitzii. KEGG function prediction indicated that bacterial colony function was primarily related to carbohydrate metabolism, amino acid metabolism, and energy metabolism. Plasma metabolomic analysis identified 16 differentially accumulated metabolites between the nPDP and PDP groups, with notable contributions from 12-ketodeoxycholic acid (12-KCAc), dihydroouabain (DHO), and lysophosphatidic acid (LysoPA). Furthermore, a significant negative correlation was observed between LysoPA and Faecalibacterium, while 12-ketodeoxycholic acid exhibited a positive correlation with Clostridium and Romboutsia. This study suggests that PDP patients have distinct gut microbiota and metabolic profiles, which may contribute to the pain experience in PD patients. These divergent microbial and metabolite signatures may provide insight into potential mechanisms linking the gut-brain axis to pain in PD.
