Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism
The human gut microbiota metabolizes the Parkinson’s disease medication Levodopa (l-dopa), potentially reducing drug availability and causing side effects. However, the organisms, genes, and enzymes responsible for this activity in patients and their susceptibility to inhibition by host-targeted drugs are unknown. Here, we describe an interspecies pathway for gut bacteriall-dopa metabolism. Conversion ofl-dopa to dopamine by a pyridoxal phosphate-dependent tyrosine decarboxylase fromEnterococcus faecalisis followed by transformation of dopamine tom-tyramine by a molybdenum-dependent dehydroxylase fromEggerthella lenta. These enzymes predict drug metabolism in complex human gut microbiotas. Although a drug that targets host aromatic amino acid decarboxylase does not prevent gut microbiall-dopa decarboxylation, we identified a compound that inhibits this activity in Parkinson’s patient microbiotas and increasesl-dopa bioavailability in mice.