Mitigation of Gut Bacterial Metabolism of Levodopa Could Enhance Its Efficacy

The drug levodopa is used to manage Parkinson’s disease. As the disease progresses, patients with Parkinson’s disease require increased doses of levodopa, which can cause undesirable side effects. The oral bioavailability of levodopa decreases in patients with Parkinson’s disease due to the increased metabolism of levodopa to dopamine by the gut bacteria Enterococcus faecalis. This results in decreased neuronal uptake and dopamine formation.

The article, titled “Mitigating gut microbial degradation of levodopa and enhancing brain dopamine: Implications in Parkinson’s disease” and published in Communications Biology, suggests that a promising therapeutic approach to enhance the bioavailability of levodopa may be to decrease bacterial metabolism. In this article, the authors show that Mito-ortho-HNK (mitochondria-targeted honokiol) mitigates the metabolism of levodopa (used alone or combined with carbidopa) to dopamine. The authors found that Mito-ortho-HNK suppresses the growth of E. faecalis, decreases dopamine levels in the gut, and increases dopamine levels in the brain. Mitigation of the gut bacterial metabolism of levodopa could enhance its efficacy.

Authors of the article are Gang Cheng, PhD, assistant professor of biophysics; Micael Hardy, PhD, of Aix-Marseille Université, France; Jimmy Feix, PhD, professor of biophysics; Cecilia Hillard, PhD, associate dean for research, professor of pharmacology and toxicology, the G. Frederick Kasten, Jr. Endowed Chair in Parkinson’s Disease Research and director of the Neuroscience Research Center; and Balaraman Kalyanaraman, PhD, professor of biophysics and the Harry R. & Angeline E. Quadracci Professor in Parkinson’s Research.