Gut bacterial tyrosine decarboxylase activity impacts the levodopa pharmacokinetics in patients with Parkinsons disease

Small intestinal bacteria harboring tyrosine decarboxylase (TDC) activity have been shown to reduce levels of the main treatment for Parkinsons disease (PD), levodopa. However, it remains obscure whether the relative abundance of faecal bacterial-TDC contributes to the reduced plasma levodopa bioavailability and the frequency of dosage regimen of levodopa treatment. Shotgun metagenomic sequencing of 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 was significantly different between PD patients compared to their controls. Independently, in vitro TDC-bacterial activity was determined and showed significant negative correlation with the plasma levels of the total absorbed levodopa measured over five hours in all PD patients, while TDC-bacterial relative abundance correlated positively with the total daily levodopa dosage in PD patients. Overall, the data infers a significant contribution of TDC-bacterial species to the decreased levodopa bioavailability in PD patients, thus representing significant progress toward improving the treatment of PD.