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Nat Commun. 2019 Jan 18;10(1):310. doi: 10.1038/s41467-019-08294-y.

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

Author information

1
Department of Molecular Immunology and Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.
2
Faculty of Pharmacy, Department of Microbiology and Immunology, Beni-Suef University, Beni-Suef, 62514, Egypt.
3
Division of Digestive Disease and Nutrition, Section of Gastroenterology, Department of Internal Medicine, Rush University Medical Center, 1725 W. Harrison, Suite 206, Chicago, Illinois, 60612, USA.
4
Department of Behavioral Neuroscience, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.
5
Department of Molecular Immunology and Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands. sahar.elaidy@rug.nl.

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.

PMID:
30659181
PMCID:
PMC6338741
DOI:
10.1038/s41467-019-08294-y
[Indexed for MEDLINE]
Free PMC Article

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