Fecal tyrosine decarboxylase and motor response complications in Parkinson's disease

Gut microbe-derived tyrosine decarboxylase (TDC) was recently discovered to metabolize levodopa, potentially reducing its bioavailability and aggravating motor dysfunction in Parkinson's disease (PD) through fluctuating dopaminergic stimulation. We aimed to investigate the clinical significance of fecal tdc (TDC gene) abundance in PD patients, focusing on its association with motor response complications (MRC).

Fecal samples were collected from 178 PD patients (mean age = 67.7 ± 8.7years; median Hoehn and Yahr stage = 2.0[1.0]; median disease duration = 7.0[8.0]years) who underwent evaluations of motor severity (MDS-UPDRS), cognitive function (MoCA), and constipation severity (PAC-SYM). Fecal tdc abundance was quantified via real-time polymerase chain reaction.

Fecal tdc abundance showed high interindividual variability, with a trend for higher levels in patients with MRC (n = 85) compared to those without (n = 93) (median [IQR], 1.6 × 10⁸ [21.3 × 10⁸] vs. 0.6 × 10⁸ [7.0 × 10⁸], p = 0.109; mean difference 10.1 × 10⁸ [95 % CI: -8.7 × 10⁸, 28.9 × 10⁸], p = 0.293). Patients with dyskinesia and motor fluctuations had 2.9-fold and 2.3-fold higher fecal tdc abundances, respectively, compared to those without, although differences were not significant. In the overall cohort, fecal tdc abundance correlated mildly with levodopa equivalent daily dose (LEDD, r_s = 0.16, p = 0.035). A similar mild correlation with LEDD was observed in the subgroup of patients with motor fluctuations (r_s = 0.22, p = 0.045).

Elevated fecal tdc abundance may be associated with higher levodopa requirements in PD. However, no statistically significant association was found with MRC. Further investigations are warranted to explore its utility as a disease biomarker and/or therapeutic target in PD.