The role of gut microbiota tyrosine decarboxylases in levodopa pharmacokinetics: insights from a levodopa challenge test

The gut microbiota is known to influence levodopa metabolism in the intestinal tract, primarily through the action of tyrosine decarboxylase, an enzyme encoded by the tyrosine decarboxylase gene (tyrDC). However, the effect of the abundance of the tyrDC gene on levodopa pharmacokinetics remains unclear. The aim of this study was to investigate this relationship in Parkinson’s disease (PD) patients undergoing a levodopa challenge test. Our study enrolled 12 PD patients with a good response to levodopa. Plasma levodopa pharmacokinetics were determined via liquid chromatography‒tandem mass spectrometry, while tyrDC gene abundance in faecal samples was assessed via metagenomic shotgun sequencing. A total of 12 PD patients (age: 58.00 ± 8.80 years) with an Hoehn and Yahr stage of 2.25 (2.0–3.0) and a disease duration of 8.46 ± 4.94 years were enrolled. After levodopa administration, the MDS-UPDRS-III score decreased 71.28%±17.09%. We found no significant association between tyrDC gene abundance and levodopa pharmacokinetics. These findings indicate that the influence of the intestinal microbiota on PD patients with a good response to levodopa during the levodopa challenge test may be minimal, which may provide new insight into levodopa therapy.