Microbial Metabolism of Levodopa as an Adjunct Therapeutic Target in Parkinson's Disease.
Microbial Metabolism of Levodopa as an Adjunct Therapeutic Target in Parkinson's Disease.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Milwaukee, US · Author affiliation
Department of Biophysics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.Location evidence
Marseille, FR · Author affiliation
ICR (UMR 7273), CNRS, Aix-Marseille Université, 13013 Marseille, France.Location evidence
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Original abstract
Parkinson's disease is the second leading neurodegenerative disease of aging. For over five decades, oral levodopa has been used to manage the progressive motor deficits that are the hallmark of the disease. However, individual dose requirements are highly variable, and patients typically require increased levodopa dosage as the disease progresses, which can cause undesirable side effects. It has become increasingly apparent that the gut microbiome can have a major impact on the metabolism and efficacy of therapeutic drugs. In this Perspective, we examine recent studies highlighting the impact of metabolism by Enterococcus faecalis, a common commensal gut bacterium, on levodopa bioavailability. E. faecalis expresses a highly conserved tyrosine decarboxylase that promiscuously converts levodopa to dopamine in the gut, resulting in decreased neuronal uptake of levodopa and reduced dopamine formation in the brain. Mitochondria-targeted antioxidants conjugated to a triphenylphosphonium moiety have shown promise in transiently suppressing the growth of E. faecalis and decreasing microbial levodopa metabolism, providing an approach to modulating the microbiome that is less perturbing than conventional antibiotics. Thus, mitigating metabolism by the gut microbiota is an attractive therapeutic target to preserve and potentiate the efficacy of oral levodopa therapy in Parkinson's disease.