The Determination of Trimethylamine N-Oxide and Organic Acids Connected with Gut Microbiota in the Urine of Parkinson’s Disease Patients: A Pilot Study

Parkinson's disease (PD) progression appears closely tied to gut microbiota alterations, with microbial metabolites potentially influencing neurodegeneration. This pilot study employed GC-MS and LC-MS/MS to analyze the urinary levels of gut-derived metabolites-including succinic acid, <i>p</i>-hydroxyphenylacetic acid, homovanillic acid (HVA), vanillylmandelic acid (VMA), adipic acid, and trimethylamine N-oxide (TMAO)-in 20 PD patients versus 20 age-matched controls. The key findings revealed that PD patients exhibited significantly elevated succinic acid (<i>p</i> = 0.0018) and HVA (<i>p</i> = 0.0002) levels alongside reduced TMAO (<i>p</i> = 1.65 × 10^-5). Notably, succinic acid showed an inverse correlation with disease severity (Hoehn and Yahr scale: r = -0.63; <i>p</i> = 0.0028), while TMAO demonstrated a strong positive association (r = 0.81; <i>p</i> = 0.00001). The elevated HVA, a dopamine metabolite, may serve as a potential biomarker for monitoring levodopa treatment efficacy. These results suggest that gut microbiota metabolites contribute to PD pathogenesis, with TMAO and succinic acid emerging as promising biomarkers for tracking disease progression. This study highlights the clinical potential of non-invasive urinary metabolite profiling using GC-MS and LC-MS/MS techniques. However, further investigation through larger-scale studies is needed to confirm these findings and elucidate the underlying mechanisms connecting gut microbiota dysbiosis to PD neurodegeneration.