Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease
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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.
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Microbiota dysbiosis in PD could reduce the availability of levodopa.
“This suggests that microbiota dysbiosis in PD could reduce the availability of levodopa [156, 157].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [156]
Carbidopa is not effective against bacterial dopa decarboxylases, enabling the gut microbiota to metabolize L-dopa, decreasing drug availability while increasing side effects.
“carbidopa is not effective against the bacterial dopa decarboxylases [180], and this enables the GM to metabolize L-dopa, decreasing the drug availability while increasing the side effects [180,181]”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [180]
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- Authors
- van Kessel, S. P., Frye, A. K., El-Gendy, A. O., Castejon, M., Keshavarzian, A., van Dijk, G., & El Aidy, S.
- Affiliations
- University of Groningen (NL)
- Beni-Suef University (EG)
- Rush University Medical Center (US)
- Venue
- Nature Communications
- Published
- 2019-01-18
- Volume
- 10
- Issue
- 1
- Pages
- 310-310
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6338741
- OpenAlex
- W2911442568
- Cited by
- 521
- References
- 43
- Citations by year
- 2026: 53 · 2025: 68 · 2024: 80 · 2023: 71 · 2022: 90 · 2021: 78 · 2020: 51 · 2019: 30
- FWCI
- 42.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Funders
- Rush University
- European Commission
- Rijksuniversiteit Groningen
- Wageningen University and Research
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- gut microbiota, tyrosine decarboxylase, levodopa, Parkinson's disease, dopamine, levodopa metabolism, proximal small intestine, drug availability, microbial metabolism, levodopa dosage, competitive substrate inhibition
- MeSH terms
- Gastrointestinal Microbiome, Aged, Aged, 80 and over, Animals, Antiparkinson Agents, Bacteria, Female, Humans, Intestine, Small, Levodopa, Male, Middle Aged, Parkinson Disease, Tyrosine Decarboxylase, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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