Gut microbiota-derived metabolite trimethylamine N-oxide as a biomarker in early Parkinson's disease

Abstract

Objectives: This study aimed to investigate the potential of using changes in the plasma levels of trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, as a biomarker in early Parkinson&apos;s disease (PD). Methods: Plasma TMAO levels were measured in 85 patients with drug-naive early stage PD and 20 healthy controls. A linear mixed model was used to assess longitudinal changes in levodopa-equivalent dose (LED) during follow-up (>2 y) in three tertile PD groups according to plasma TMAO levels. Additionally, a Cox regression analysis was performed to assess the effect of plasma TMAO levels on dementia conversion. Results: Plasma TMAO levels of patients with PD were lower than those of healthy controls. A linear mixed model demonstrated that patients with PD and lower levels of TMAO (<4.75 mu mol/L; i.e., lowest tertile group) exhibited faster increases in LED over time. The Cox regression model did not reveal that plasma TMAO level was associated with the risk for dementia conversion (P = 0.488). However, when we divided patients with PD into two subgroups according to bet cutoff TMAO level to maximize the log-rank statistics, the PD group with a low plasma TMAO level (<6.92 mu mol/L) had a higher risk (with borderline statistical significance) for PD-dementia conversion than the group with a high TMAO level (hazard ratio: 7.565; 95% confidence interval, 1.004-57.019; P = 0.050). Conclusions: The results demonstrate that lower baseline plasma TMAO levels are associated with faster increases in LED and tend to increase the risk for PD-dementia conversion, suggesting the prognostic implications of TMAO in early stage PD.