Contributions of Gut Bacteria and Diet to Drug Pharmacokinetics in the Treatment of Parkinson's Disease.

Parkinson's disease is the second-most common neurodegenerative disorder worldwide. Besides deciphering the mechanisms that underlie the etiology of the disease, it is important to elucidate the factors that influence the efficacy of the treatment therapeutics. Levodopa, which remains the golden treatment of the disease, is absorbed in the proximal small intestine. A reduction in levodopa absorption, leads to reduction in striatal dopamine levels and, in turn, an "off"-episode. In fact, motor fluctuations represent a major problem during the progression of the disease and alteration between "on" (mobility often with dyskinesia) and "off" (immobility, akinesia) episodes contribute to a decreased quality of life. Dietary amino acids can interfere with the absorption of levodopa from the gut lumen and its transport through the blood brain barrier. In addition, higher abundance of specific gut bacteria that restrict levodopa absorption plays a significant role in motor fluctuations in a subset of Parkinson's disease patients. Here, we review the impact of factors potentially interfering with levodopa absorption, focusing on levodopa transport, diet, and gut bacterial interference with the bioavailability of levodopa.