Levodopa is converted into dopamine in the brain and is the standard oral treatment for Parkinson’s disease. To boost levodopa’s delivery, clinicians often prescribe catechol-O-methyltransferase inhibitors (COMT inhibitors), drugs designed to block body enzymes that would otherwise modify levodopa into forms that cannot cross the blood–brain barrier.
New research from Yale School of Medicine, published in Nature Microbiology, shows a counterproductive effect. The study team, led by postdoctoral associate Andrew Verdegaal in the lab of senior author Andrew Goodman, PhD, reports that COMT inhibitors also have antibacterial activity. By killing bacteria that are susceptible to the drug, COMT inhibitors change gut-microbiome composition and can allow other species to expand.
One important consequence is the rise of Enterococcus faecalis, which carries an enzyme able to metabolize levodopa in the gut. When E. faecalis levels increase, more levodopa is broken down before it can reach the brain, reducing the drug’s efficacy. The authors note this interaction occurs through the microbiome rather than the liver and that the finding supports earlier links between higher E. faecalis and reduced levodopa benefit.
The study concludes that researchers and clinicians should examine how the microbiome affects responses to co‑prescribed drugs. The research received support from the National Institutes of Health and Yale University, and the authors take responsibility for the content.
Difficult words
- levodopa — a drug converted into dopamine in brain
- catechol-O-methyltransferase inhibitor — a drug that blocks enzymes changing levodopacatechol-O-methyltransferase inhibitors
- blood–brain barrier — a barrier controlling exchange between blood and brain
- microbiome — the community of microorganisms living in body
- metabolize — to chemically change a substance inside organism
- efficacy — how well a treatment produces the intended result
- susceptible — likely to be affected or harmed by something
- antibacterial activity — action that kills or stops bacterial growth
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- How might changes in the gut microbiome affect a patient’s response to levodopa? Give reasons.
- What should researchers and clinicians study about the microbiome and co-prescribed drugs to improve treatment outcomes?
- How could this finding change how doctors prescribe medications for Parkinson’s disease?
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