IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-08294-y.html
   My bibliography  Save this article

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

Author

Listed:
  • Sebastiaan P. Kessel

    (University of Groningen)

  • Alexandra K. Frye

    (University of Groningen)

  • Ahmed O. El-Gendy

    (University of Groningen
    Beni-Suef University)

  • Maria Castejon

    (University of Groningen)

  • Ali Keshavarzian

    (Rush University Medical Center)

  • Gertjan Dijk

    (University of Groningen)

  • Sahar El Aidy

    (University of Groningen)

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.

Suggested Citation

  • Sebastiaan P. Kessel & Alexandra K. Frye & Ahmed O. El-Gendy & Maria Castejon & Ali Keshavarzian & Gertjan Dijk & Sahar El Aidy, 2019. "Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08294-y
    DOI: 10.1038/s41467-019-08294-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-08294-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-08294-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Deborah A. Hall & Robin M. Voigt & Thaisa M. Cantu-Jungles & Bruce Hamaker & Phillip A. Engen & Maliha Shaikh & Shohreh Raeisi & Stefan J. Green & Ankur Naqib & Christopher B. Forsyth & Tingting Chen , 2023. "An open label, non-randomized study assessing a prebiotic fiber intervention in a small cohort of Parkinson’s disease participants," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Zachary D. Wallen & Ayse Demirkan & Guy Twa & Gwendolyn Cohen & Marissa N. Dean & David G. Standaert & Timothy R. Sampson & Haydeh Payami, 2022. "Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08294-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.