Gut bacterial tyrosine decarboxylase gene abundance associates with disease duration, medication exposure, and gastrointestinal symptoms in a longitudinal cohort of Parkinson’s disease patients

Abstract

Gut microbiota influences the clinical response of a wide variety of orally administered drugs. However, the underlying mechanisms by which drug-microbiota interactions occur are still obscure. Previously, we reported that tyrosine decarboxylating (TDC) bacteria may restrict the levels of levodopa reaching the circulation in patients with Parkinson's disease (PD). We observed a significant positive association between disease duration and the abundance of the bacterial tdc-gene. The question arises whether increased exposure to anti-PD medication could affect the abundance of bacterial TDC, to ultimately impact drug efficacy. To this end, we investigated the potential association between anti-PD drug exposure and bacterial tdc-gene abundance over a time period of two years in a longitudinal cohort of PD patients and healthy controls. Our data reveal significant associations between tdc-gene abundance, anti-PD medication, and gastrointestinal symptoms and warrants further research on the effect of anti-PD medication on microbial changes and gastrointestinal-function.

The Gut Microbiome in Parkinson’s Disease: A Longitudinal Study of the Impacts on Disease Progression and the Use of Device-Assisted Therapies

“…These differences have been associated with a variety of disease severities ( Barichella et al, 2019 ), proposed to be mediated through an influence on gut permeability and colonic inflammation, which may facilitate α-syn aggregation and propagation in the local gastrointestinal environment ( Bullich et al, 2019 ; Lubomski et al, 2020c ; Romano et al, 2021 ). Furthermore, evidence suggests that certain microbiota, namely Lactobacillus and Enterococcus faecalis , can affect metabolism of Levodopa through increased tyrosine decarboxylase gene expression ( Maini Rekdal et al, 2019 ; van Kessel et al, 2019 , 2021 ) and could be exploited as a therapeutic target to improve Levodopa efficacy ( Lubomski et al, 2019 ). Likewise, it is increasingly recognized that certain PD treatments, in particular the device-assisted therapies (DATs) can influence the GM via the gut-brain-axis, either through direct influence on the gut [Levodopa-Carbidopa Intestinal Gel (LCIG)] and or remote to the gut [Deep Brain Stimulation (DBS)] ( Lubomski et al, 2020c , 2021c ).…”