Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease
Sebastiaan P van Kessel,Alexandra K. Frye,Ahmed O. El-Gendy,Maria Castejon,Ali Keshavarzian,Gertjan van Dijk,Sahar El Aidy +6 more
TLDR
The authors show that bacterial tyrosine decarboxylases (TDC) decrease the levels of levodopa, the primary treatment in Parkinson’s disease, by conversion to dopamine, and suggest TDC as a potential predictive biomarker for treatment.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.read more
Citations
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The gut microbiota-brain axis in behaviour and brain disorders.
TL;DR: Emerging and exciting evidence of intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the Gut microbiota to neurological disorders are discussed.
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The gut microbiome in neurological disorders.
TL;DR: Research into the role of the gut microbiome in modulating brain function has rapidly increased over the past 10 years, albeit chiefly in animal models, and interpretation of such data is often difficult given that the composition of the microbiome is influenced by various factors such as diet and exercise.
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Gastrointestinal Dysfunction in Parkinson’s Disease
TL;DR: Bowel management for these people must remain empirical until well-designed controlled trials with adequate numbers and clinically relevant outcome measures become available, according to the conclusion from the latest Cochrane review on treatment of bowel dysfunction in central neurological diseases.
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Gut microbial metabolites as multi-kingdom intermediates
TL;DR: The major classes of microbial metabolites are discussed, examples of how microbial metabolites affect host health are highlighted and a potential framework for integration of discovery-based metabolite studies with mechanistic work is provided.
Journal ArticleDOI
Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism.
Vayu Maini Rekdal,Elizabeth N. Bess,Elizabeth N. Bess,Jordan E. Bisanz,Peter J. Turnbaugh,Emily P. Balskus +5 more
TL;DR: The major proposed pathway involves an initial decarboxylation of l-dopa to dopamine, followed by conversion of dopamine to m-tyramine by means of a distinctly microbial dehydroxylation reaction.
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Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease
Timothy R. Sampson,Justine W. Debelius,Taren Thron,Stefan Janssen,Gauri G. Shastri,Zehra Esra Ilhan,Collin Challis,Catherine E. Schretter,Sandra Rocha,Viviana Gradinaru,Marie-Françoise Chesselet,Ali Keshavarzian,Kathleen M. Shannon,Rosa Krajmalnik-Brown,Pernilla Wittung-Stafshede,Rob Knight,Sarkis K. Mazmanian +16 more
TL;DR: It is reported herein that gut microbiota are required for motor deficits, microglia activation, and αSyn pathology, and suggested that alterations in the human microbiome represent a risk factor for PD.
Journal ArticleDOI
Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis
Jessica M. Yano,Kristie B. Yu,Gregory P. Donaldson,Gauri G. Shastri,Phoebe Ann,Liang Ma,Cathryn R. Nagler,Rustem F. Ismagilov,Sarkis K. Mazmanian,Elaine Y. Hsiao +9 more
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Journal ArticleDOI
Gut microbiota are related to Parkinson's disease and clinical phenotype.
Filip Scheperjans,Velma T. E. Aho,Pedro A. B. Pereira,Kaisa Koskinen,Lars Paulin,Eero Pekkonen,Elena Haapaniemi,Seppo Kaakkola,Johanna Eerola-Rautio,Marjatta Pohja,Esko Kinnunen,Kari Murros,Petri Auvinen +12 more
TL;DR: The findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype, and the suitability of the microbiome as a biomarker is warranted.
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