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

APA

van Kessel, S. P., Frye, A. K., El-Gendy, A. O., Castejon, M., Keshavarzian, A., van Dijk, G., & El Aidy, S. (2019). Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease. Nature Communications, 10(1), [310]. https://doi.org/10.1038/s41467-019-08294-y

Author

van Kessel, Sebastiaan P ; Frye, Alexandra K ; El-Gendy, Ahmed O ; Castejon, Maria ; Keshavarzian, Ali ; van Dijk, Gertjan ; El Aidy, Sahar. / Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease. In: Nature Communications. 2019 ; Vol. 10, No. 1.

Harvard

van Kessel, SP, Frye, AK, El-Gendy, AO, Castejon, M, Keshavarzian, A, van Dijk, G & El Aidy, S 2019, 'Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease' Nature Communications, vol. 10, no. 1, 310. https://doi.org/10.1038/s41467-019-08294-y

Standard

Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease. / van Kessel, Sebastiaan P; Frye, Alexandra K; El-Gendy, Ahmed O; Castejon, Maria; Keshavarzian, Ali; van Dijk, Gertjan; El Aidy, Sahar.

In: Nature Communications, Vol. 10, No. 1, 310, 18.01.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

van Kessel SP, Frye AK, El-Gendy AO, Castejon M, Keshavarzian A, van Dijk G et al. Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease. Nature Communications. 2019 Jan 18;10(1). 310. https://doi.org/10.1038/s41467-019-08294-y


BibTeX

@article{23077b75dabe45749397421934689b15,
title = "Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease",
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.",
keywords = "INTESTINAL MICROBIOTA, L-DOPA, EXPRESSION, OVERGROWTH, METABOLISM, HOST, PCR",
author = "{van Kessel}, {Sebastiaan P} and Frye, {Alexandra K} and El-Gendy, {Ahmed O} and Maria Castejon and Ali Keshavarzian and {van Dijk}, Gertjan and {El Aidy}, Sahar",
year = "2019",
month = "1",
day = "18",
doi = "10.1038/s41467-019-08294-y",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease

AU - van Kessel, Sebastiaan P

AU - Frye, Alexandra K

AU - El-Gendy, Ahmed O

AU - Castejon, Maria

AU - Keshavarzian, Ali

AU - van Dijk, Gertjan

AU - El Aidy, Sahar

PY - 2019/1/18

Y1 - 2019/1/18

N2 - 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.

AB - 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.

KW - INTESTINAL MICROBIOTA

KW - L-DOPA

KW - EXPRESSION

KW - OVERGROWTH

KW - METABOLISM

KW - HOST

KW - PCR

U2 - 10.1038/s41467-019-08294-y

DO - 10.1038/s41467-019-08294-y

M3 - Article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 310

ER -

ID: 74427033