Bacterial deamination of residual levodopa medication for Parkinson's disease elicits inhibitory effect on gut motility [article]

Sebastiaan P van Kessel, Hiltje Riemke de Jong, Simon Laurens Winkel, Sander Sebastiaan van Leeuwen, Sieger Adriaan Nelemans, Hjalmar Permentier, Ali Keshavarzian, Sahar El Aidy
2020 bioRxiv   pre-print
Parkinson's disease is associated with gastrointestinal tract dysfunction, where constipation is reported as the most common gastrointestinal symptom. Aromatic bacterial metabolites are attracting considerable attention due to their application on gut homeostasis and host's physiology. Clostridium sporogenes is a key contributor to the production of these bioactive metabolites in the human gut. Here, we show that C. sporogenes effectivelys deaminate non-proteinogenic aromatic amino acids, such
more » ... amino acids, such as levodopa, the main treatment in Parkinson's disease, and identify the aromatic aminotransferase responsible for the deamination. The deaminated metabolite from levodopa, 3-(3,4-dihydroxyphenyl) propionic acid, is detected in fecal samples of Parkinson's disease patients on levodopa medication, elicits an inhibitory effect on gut motility. Overall, this study underpins the importance of the metabolic pathways of the gut microbiome involved in drug metabolism not only to preserve drug effectiveness, but also to avoid potential side effects of bacterial breakdown products of the unabsorbed residue of medication.
doi:10.1101/2020.02.13.945717 fatcat:yjrpxwho6bd7lm2svm6ab73ntm