Gut bacterial deamination of residual levodopa medication for Parkinson’s disease

BMC Biology

Hiltje R. de Jong¹  Sebastiaan P. van Kessel¹  Simon L. Winkel¹  Sahar El Aidy¹  Sander S. van Leeuwen²  Sieger A. Nelemans³  Ali Keshavarzian⁴  Hjalmar Permentier⁵ 

[1] Department of Molecular Immunology and Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands;Department of Molecular Immunology and Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands;Current Address: Department of Laboratory Medicine, Cluster Human Nutrition & Health, University Medical Center Groningen (UMCG), Hanzeplein 1, 9713 GZ, Groningen, The Netherlands;Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands;Division of Digestive Disease and Nutrition, Section of Gastroenterology, Department of Internal Medicine, Rush University Medical Center, 1725 W. Harrison, Suite 206, 60612, Chicago, IL, USA;Interfaculty Mass Spectrometry Center, University of Groningen, Groningen, The Netherlands;

关键词: Non-motor symptoms;    Gastrointestinal motility;    Clostridium sporogenes;    Drug side effects;    Bioactive metabolites;    Aminotransferase;   

DOI  :  10.1186/s12915-020-00876-3

来源: Springer

【 摘 要 】

BackgroundParkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms. Gastrointestinal tract dysfunction is one of the non-motor features, where constipation is reported as the most common gastrointestinal symptom. Aromatic bacterial metabolites are attracting considerable attention due to their impact on gut homeostasis and host’s physiology. In particular, Clostridium sporogenes is a key contributor to the production of these bioactive metabolites in the human gut.ResultsHere, we show that C. sporogenes deaminates levodopa, the main treatment in Parkinson’s disease, and identify the aromatic aminotransferase responsible for the initiation of the deamination pathway. The deaminated metabolite from levodopa, 3-(3,4-dihydroxyphenyl)propionic acid, elicits an inhibitory effect on ileal motility in an ex vivo model. We detected 3-(3,4-dihydroxyphenyl)propionic acid in fecal samples of Parkinson’s disease patients on levodopa medication and found that this metabolite is actively produced by the gut microbiota in those stool samples.ConclusionsLevodopa is deaminated by the gut bacterium C. sporogenes producing a metabolite that inhibits ileal motility ex vivo. Overall, this study underpins the importance of the metabolic pathways of the gut microbiome involved in drug metabolism not only to preserve drug effectiveness, but also to avoid potential side effects of bacterial breakdown products of the unabsorbed residue of medication.

【 授权许可】

CC BY