Implications of Parkinson’s disease-associated alterations in the oral and gut microbiome on vitamin B12 biosynthesis and levodopa bioavailability

Abstract Small intestinal bacteria harboring tyrosine decarboxylase (TDC) activity was shown to reduce levels of the main treatment for Parkinson’s disease (PD), levodopa. However, it remains obscure whether the relative abundance of bacterial-TDC in the oral cavity and/or feces contributes to the decreased levodopa bioavailability and the frequency of dosage regimen of levodopa treatment. Shotgun metagenomic sequencing of saliva and fecal samples collected from 19 PD patients requiring various levodopa dosage regimens (consumed between 2 and 7 times per day; dosage range between 300-1400 mg) and 16 age-matched household spousal healthy control subjects was employed. The composition of TDC- harboring bacteria differed between oral and fecal samples, as well as between fecal samples from PD patients compared to their controls. TDC-bacterial activity showed significant negative correlation with plasma levodopa levels measured over five hours in all PD patients, while TDC-bacterial relative abundance correlated positively with the daily levodopa dosage in PD patients on high frequency levodopa dosage regimen. PD fecal samples had markedly lower relative abundance of short-chain fatty acids-producing bacteria. Functional analyses revealed differences in microbiota metabolism in PD involving lower vitamin B12 biosynthesis. Our data revealed a significant contribution of TDC to the decreased levodopa bioavailability and differences in fecal, but not the overall oral microbiota composition and metabolism between PD patients and their controls. These findings suggest that PD-associated alterations of the gut, but not oral microbiome, may render considerable functional gene profiling differences affecting levodopa bioavailability, host metabolism and motor-fluctuations.