Objective: To Investigate the clinical relevance of tyrosine decarboxylating (TDC)-bacteria in patients with Parkinson’s Disease (PD).

Background: Recently, we have shown that TDC-gut bacteria that can decarboxylate levodopa to dopamine in the gut, are associated with i) lower levels of levodopa in the blood circulation in a rat model, ii) higher frequency of levodopa dosage regimen as well as with duration of the disease in PD patients (1). Thus, we postulated that the higher frequency of levodopa dosage regimen and TDC-bacteria can create a vicious circle, where increased TDC-bacteria will ultimately result in higher levodopa dosage requirement (1). Additionally, we found that the unabsorbed residues of levodopa can be converted by gut microbiota to another bioactive molecule, which affects ileal contractility ex vivo (2). The latter may favor the colonization of (TDC)-bacteria, further contributing to the vicious circle, and potentially compounding the issue of motor fluctuations.

Method: Nineteen PD patients and sixteen matching healthy spouses (HS) were recruited at RUMC. The PD patients were selected based on the frequency (high (>5x per day) versus low (3-4x/day)) of their levodopa dosage intake. Blood samples were collected to study the pharmacokinetics of Levodopa, and the pharmacodynamics was assessed via a finger-tap test for PD patients. As an indicator for possible overgrowth of TDC-bacteria, a lactulose breath test was performed. Participants filled in questionnaires about their food intake, GI Symptom and Severity Checklist. Fecal and saliva samples were collected to assess the colonic and oral microbiota profiles, respectively, using shotgun metagenomic sequencing.

Results: Differences in the abundance of tdc-gene encoding bacteria as well as overall microbiome are currently assessed. Readout of lactulose breath test and TDC-activity in saliva and fecal samples are analyzed to establish whether oral or fecal microbiota is a better predictor of TDC-bacterial activity in the small intestine.  Finally, associations between the above-mentioned parameters and GI Symptoms will be assessed.

Conclusion: Our data will determine if TDC-bacterial activity is a predictor of the frequency of levodopa intake. Moreover, the data will provide insight into the interaction between levodopa, GI symptoms and altered microbiome in patients with PD.

References: 1. van Kessel SP, Frye AK, El-Gendy AO, Castejon M, Keshavarzian A, van Dijk G, El Aidy S. Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease. Nat Commun (2019) 10:310. 2. van Kessel SP, de Jong HR, Winkel SL, van Leeuwen SS, Nelemans SA, Permentier H, Keshavarzian A, El Aidy S. Gut bacterial deamination of residual levodopa medication for Parkinson’s disease. BMC Biol (2020) 18:137.

« Back to MDS Virtual Congress 2021

MDS Abstracts - https://www.mdsabstracts.org/abstract/gut-bacterial-tyrosine-decarboxylase-as-a-predictive-biomarker-to-identify-parkinsons-disease-patients-with-motor-fluctuations-requiring-frequent-levodopa-administration/