Identifying Metabolites Produced During Gut Microbial Metabolism of Parkinson's Medication

The current gold standard treatment for Parkinson’s Disease is levodopa, which is an orally ingested central nervous system agent that gains therapeutic efficacy after being converted into dopamine in the brain. While current methods exist to evaluate treatment efficacy and prescribe targeted therapies to prevent its premature metabolism, they do not consider the presence of drug-metabolizing enzymes encoded by bacteria in our microbiome. An interspecies bacterial pathway has recently been identified that prematurely converts L-dopa to dopamine in the gut and reduces the available concentration to carry out the target effect. In this work, an untargeted, metabolomic approach was used to detect and quantify volatile metabolites produced during levodopa metabolism in E. faecalis OG1RF cultures. The compounds produced during this process serve as the direct products of bacterial drug modifications by E. faecalis that solely occur in the presence of levodopa. By employing GC-MS techniques to quantify these products, potential confirmative biomarkers can be identified that evaluate treatment efficacy across patients. The unique metabolites identified in this study hold the potential to eventually serve as biomarkers for Parkinson’s treatment efficacy and provide insight to the functional characteristics of E. faecalis levodopa metabolism across the 10 million patients of Parkinson’s Disease. In future efforts, the identity of these metabolites will be verified along with their significant association to L-dopa metabolism.