Publication

Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease

van Kessel, S. P., Frye, A. K., El-Gendy, A. O., Castejon, M., Keshavarzian, A., van Dijk, G. & El Aidy, S., 18-Jan-2019, In : Nature Communications. 10, 1, 310.

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number310
JournalNature Communications
Volume10
Issue number1
Publication statusPublished - 18-Jan-2019
Related Press / Media
  1. Gut Bacteria Could Alter Parkinson's Treatment Efficacy

    Sahar El Aidy

    21/01/2019

    1 item of media coverage

    Press/Media: Public Engagement ActivitiesProfessional

  2. How Gut Bacteria Affect the Treatment of Parkinson's Disease

    Sahar El Aidy

    21/01/2019

    1 item of media coverage

    Press/Media: Public Engagement ActivitiesProfessional

View all (9) »

View graph of relations

Download statistics

No data available

ID: 74427033