Neurology: The relationship between the microbial tyrosine decarboxylase gene and levodopa responsiveness in patients with Parkinson's disease

Individual differences in the efficacy of levodopa are a challenge
in individualizing the treatment of Parkinson's disease (PD).
The gut microbiota may represent a new approach to
personalized medicine.
Recently, a new microbial levodopa metabolic pathway was discovered, which is mediated by tyrosine decarboxylase, mainly encoded
by the tyrosine decarboxylase gene (tyDC) in Enterococcus faecal.
A study published in Neurology sought to determine whether the abundance of the microbial tyDC gene and Enterobacter faecalius is associated with levodopa responsiveness and can predict drug response
.

The transversal study recruited patients with Parkinson's disease between December 2019 and January 2022 and evaluated levodopa responsiveness
using levodopa provocation testing.
Patients are divided into moderate and good responders based on levodopa
responsiveness.
Real-time PCR was used to detect tyDC gene and Enterobacter faecali abundance in feces
.
Plasma levodopa concentration
was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.
A predictive model of levodopa responsiveness is established and validated
by cross-validation and external validation.

A total of 101 patients with Parkinson's disease were enrolled in the primary cohort and 43 were enrolled in the external validation cohort
.
Abundance of TyrDC genes in moderately reactive respondents (3.
6 [3.
1-4.
3] vs.
2.
6 [2.
1-2.
9], P < 0.
001) and Enterococcus faecali (3.
2 [2.
5-4.
4] vs.
2.
6 [2.
1-3.
6], P = 0.
010).

TyDC gene abundance was independently associated with levodopa responsiveness (odds ratio: 5.
848; 95% confidence interval [CI] : 2.
664-12.
838; P < 0.
001).

Notably, TyrDC gene abundance showed some discrimination against levodopa responsiveness in the main cohort (sensitivity: 80.
0%; specificity: 84.
3% ; Area under curve [ AUC ] : 0.
85; 95% CI: 0.
77-0.
93; P < 0.
001) and external validation cohort (sensitivity: 85.
0%; specificity: 95.
7% ; AUC: 0.
95; 95% CI: 0.
89-1.
02; P < 0.
001).

Levodopa responsiveness predictions based on TyrDC gene abundance have good calibration and discrimination in cross-validation (C-indices of 0.
856 and 0.
851 in training and test sets, respectively) and external validation (C-index: 0.
952
).

Microbial tyDC gene abundance can be used as a potential biomarker for
levodopa reactivity.
New strategies targeting the tyDC gene may provide new avenues
for personalized treatment of levodopa.

Source: Zhang Y, He X, Mo C, et al.
Association Between Microbial Tyrosine Decarboxylase Gene and Levodopa Responsiveness in Patients With Parkinson Disease [published online ahead of print, 2022].
Aug 31].
Neurology.
2022; 10.
1212/WNL.
0000000000201204.
doi:10.
1212/WNL.
0000000000201204