Gut bacterial deamination of residual levodopa medication for Parkinson’s disease

Abstract

AbstractAromatic bacterial metabolites are attracting considerable attention due to their impact on gut homeostasis and host’s physiology.Clostridium sporogenesis a key contributor to the production of these bioactive metabolites in the human gut. Here, we show thatC. sporogenesdeaminates levodopa, the main treatment in Parkinson’s disease, and identify the aromatic aminotransferase responsible for the initiation of the deamination pathway. The deaminated metabolite from levodopa, 3-(3,4-dihydroxyphenyl)propionic acid, elicits an inhibitory effect on ileal motility in anex vivomodel. 3-(3,4-dihydroxyphenyl)propionic acid is detected in fecal samples of Parkinson’s disease patients on levodopa medication. Our data are of significant impact to the treatment of Parkinson’s disease, where constipation is reported as the most common gastrointestinal symptom. 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.