Parkinson’s disease is caused by a decrease in dopamine production. Levodopa is an oral medication that is absorbed and crosses the blood-brain barrier, where it is converted into dopamine.
“This drug is a way for the body to externally receive dopamine,” says Verdegaal. “But it has to get into the brain to have an effect.”
Some enzymes in the body can interact with the drug before it reaches the brain and convert it into a different compound that cannot cross the blood-brain barrier. COMT-Is work by blocking these enzymes before they can chemically modify levodopa, boosting the drug’s efficacy.
In the new study, however, the researchers discovered that COMT-Is have antibacterial properties that alter the microbiome. When COMT-Is kill off susceptible gut bacteria, other bacteria thrive, the researchers found. This includes Enterococcus faecalis, which contains an enzyme that can also metabolize levodopa and prevent it from reaching the brain.
The findings support previous research indicating that patients with higher levels of E. faecalis in their gut experience reduced benefit from levodopa.
“People often require co-prescription of multiple drugs,” says Verdegaal. “While Parkinson’s disease is one example, this study suggests that we should look more closely at the role of the microbiome in response to other co-prescribed drugs.”
The study also adds to growing evidence that differences in microbiomes can help explain why patients experience different effects from the same drug. “I hope our research is a stepping stone to understand this in a wider context,” Verdegaal says.
Reference: Verdegaal AA, Oh J, Javdan B, et al. A drug-microbiome-drug interaction impacts co-prescribed medications for Parkinson’s disease. Nat Microbiol. 2026. doi: 10.1038/s41564-026-02299-2
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