Objective: To investigate the clinical correlates of gut microbe-derived tyrosine decarboxylase (tdc) and motor dysfunction in Parkinson’s Disease (PD) patients.

Background: Gut microbe-derived tdc was recently discovered to metabolize levodopa (the mainstay treatment in PD), thereby reducing its bioavailability, and possibly aggravating motor dysfunction in patients with PD.

Method: Fecal samples were collected from 178 consecutive PD patients (mean age=67.7±8.7years; median Hoehn and Yahr stage=2.0[1.0] and disease duration=7.0[8.0]years), phenotyped for motor severity (MDS-UPDRS), cognitive function (MoCA), and constipation severity (PAC-SYM). Fecal tdc gene abundance was quantified via real time-polymerase chain reaction using primers TYR3f and TYR4r.

Results: Fecal tdc abundance correlated with levodopa equivalent daily dose (LEDD; rs=0.161, p=0.032), but not with age, age of PD onset, disease duration, motor severity, cognitive function, constipation severity, and individual antiparkinsonian medication group dosages in the overall cohort and the subgroup with motor response complications (MRC). Fecal tdc abundance also tended to be higher in patients with MRC (n=85) vs. those without MRC (n=93) (1.6E8[21.2E8] vs. 0.6E8[7.0E8], p=0.109). However, within the subgroup of patients with MRC, fecal tdc abundance showed no correlation with various MRC parameters (including: overall MRC severity/total score of MDS-UPDRS part 4; dyskinesia severity/MDS-UPDRS 4.1+4.2; severity [MDS-UPDRS 4.3+4.4] and unpredictability [MDS-UPDRS 4.5] of motor fluctuations), except for a correlation with shorter OFF time (MDS-UPDRS 4.3; rs=-0.263, p=0.023).

Conclusion: The association between fecal tdc abundance and increased LEDD may be clinically impactful, as it could indicate reduced medication effect due to gut bacterial metabolism. The higher intake of PD medications in these patients conceivably leads to aberrant dopaminergic stimulation and an increased incidence of MRC. Further well-designed clinical and pre-clinical studies are required to further elucidate the impact of tyrosine decarboxylase in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/fecal-tyrosine-decarboxylase-and-motor-response-complications-in-parkinsons-disease/