Title
Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease
Author
Sebastiaan P. van Kessel, Alexandra K. Frye, Ahmed O. El-Gendy, Maria Castejon, Ali Keshavarzian, Gertjan van Dijk & Sahar El Aidy
Year
2019
Journal
Nature Communications
Abstract
Human gut microbiota senses its environment and responds by releasing metabolites, some of which are key regulators of human health and disease. In this study, we characterize gut-associated bacteria in their ability to decarboxylate levodopa to dopamine via tyrosine decarboxylases. Bacterial tyrosine decarboxylases efficiently convert levodopa to dopamine, even in the presence of tyrosine, a competitive substrate, or inhibitors of human decarboxylase. In situ levels of levodopa are compromised by high abundance of gut bacterial tyrosine decarboxylase in patients with Parkinson’s disease. Finally, the higher relative abundance of bacterial tyrosine decarboxylases at the site of levodopa absorption, proximal small intestine, had a significant impact on levels of levodopa in the plasma of rats. Our results highlight the role of microbial metabolism in drug availability, and specifically, that abundance of bacterial tyrosine decarboxylase in the proximal small intestine can explain the increased dosage regimen of levodopa treatment in Parkinson’s disease patients.
Full Article
Instrument
AS-2059 autosampler
Keywords
Microbiology, Molecular biology