Parkinson’s medications may interact through gut bacteria, new study finds

Levodopa, the gold-standard treatment for Parkinson’s disease, is often given alongside medicines called catechol-O-methyltransferase inhibitors (COMT-Is) that are designed to boost its efficacy — but a new study suggests these medications may also reduce the amount of levodopa available to reach the brain.

Specifically, the data suggest treatment with COMT-Is can increase levels of certain gut bacteria that can break down levodopa. These bacteria may break down the medication in the intestines, potentially reducing how much is available to reach the brain and have its intended effects.

This study suggests a previously unrecognized interaction between two Parkinson’s medications often given in combination and highlights the need to consider the role of gut bacteria when evaluating potential interactions between different medications.

“People often require co-prescription of multiple drugs. While Parkinson’s disease is one example, this study suggests that we should look more closely at the role of [gut bacteria] in response to other co-prescribed drugs,” Andrew Albert Verdegaal, PhD, co-author of the study at Yale University, said in a university news story.

Recommended Reading

April 8, 2026 News by Patricia Inácio, PhD

Lab-made small molecule may help slow brain disease progression

Gut bacteria may play role in how Parkinson’s meds interact

The study, “A drug–microbiome–drug interaction impacts co-prescribed medications for Parkinson’s disease,” was published in Nature Microbiology. It was funded by the National Institutes of Health (NIH).

Parkinson’s is a neurological disease marked by the loss of brain cells that produce dopamine, a key signaling molecule. Low dopamine levels disrupt normal nerve signaling, ultimately leading to Parkinson’s symptoms.

Levodopa is a precursor that the body can convert into dopamine. This therapy is considered the gold-standard Parkinson’s treatment because it can boost brain dopamine levels, thereby helping to ease disease symptoms.

“This drug is a way for the body to externally receive dopamine, but it has to get into the brain to have an effect,” Verdegaal said.

COMT-Is are designed to block the activity of enzymes outside the brain that break down levodopa, thereby helping more of the active drug reach the brain. These medications are commonly given in combination with levodopa.

When researchers test for interactions between medications, they usually focus on how the two drugs affect human enzymes, particularly those in the liver, where many medicines are processed. But the human body doesn’t only contain human enzymes — it also hosts billions of bacteria and other microscopic organisms that live on and in the body.

Gut microbes can influence how the body processes medications

These microscopic organisms have their own enzymes that, in some cases, can affect drug levels, especially for medications taken by mouth, like levodopa and COMT-Is, which are absorbed through the digestive system. Previous research has shown that some gut bacteria in a group called Enterococcus can produce an enzyme that breaks down levodopa. Based on this, the researchers aimed to better understand how levodopa and COMT-Is interact with gut bacteria.

Through a series of tests in multiple lab models, the researchers found that COMT-Is can have selective antibacterial effects, meaning they can suppress certain types of bacteria. When this happens in the gut, other types of bacteria can grow to fill the space. In some cases, one of the groups that can increase is Enterococcus. These bacteria can then break down levodopa in the gut, potentially reducing the amount available to reach the brain.

“Together, these results suggest that COMT-I treatment can favor [levodopa breakdown] by human gut communities through selective antibacterial activity, leading to … subsequent Enterococcus expansion,” the researchers wrote. They added that this bacteria-driven effect of COMT-Is “may impact multiple positive and negative consequences of [levodopa] treatment, which remain to be explored.”