Gut bacteria can interfere with the effectiveness of levodopa (Sinemet)

Hardly a week goes by where there isn’t another study exploring the connection between gut bacteria and Parkinson’s Disease. While research continues to try to understand exactly how different strains of gut bacteria are involved in the development and/or progression of PD, a recent study highlights the obvious impact that differences between our unique individual microbiomes can have on how we experience PD in our daily lives.

Side note: If you are curious about this research, one of the more useful updates that I recently added to this website is the ability to search recent news items related to Parkinson’s. Here’s a link for a search for gut bacteria in the Parkinson’s news stream:

As you can see, this area of study has become a hot topic.

While we await the big answers on the connection between gut bacteria and Parkinson’s, researchers at the University of Groningen in the Netherlands have recently released a study that shows how a certain type of gut bacteria interfere with the effectiveness of levodopa drug treatment for Parkinson’s Disease.

This study, “Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease” was published in Nature Communications.

This press release from the University of Groningen does a great job of summarizing the study:

The full study is published at:

NeuroScience News also offers a great explanation of the study here:

How Gut Bacteria Affects the Treatment of Parkinson’s Disease

Gut bacteria is not an infection or medical condition. We all have gut bacteria, a complex community of microorganisms that live in our digestive tracts. Modern science refers to this our microbiome. There are as many of these bacteria cells in our body as there are our own human cells. Our body has a symbiotic relationship with these microorganisms. The composition of each person’s microbiome varies so much that we are still trying to identify and understand their differences. (For example, a recent February 2019 study just identified 2000 previously unknown species of gut bacteria. See

Back to PD…

As PD patients know, levodopa is usually taken orally, and is absorbed in the small intestine and then transported through the bloodstream, crossing the blood brain barrier to enter the brain. Decarboxylase enzymes in the gut can convert levodopa into dopamine prematurely. In contrast to levodopa, dopamine cannot cross the blood-brain barrier, so levodopa is combined with a decarboxylase inhibitor, usually carbidopa. Carbidopa prevents the levodopa to dopamine conversion in the gut, allowing it to make it to the brain.

But guess what? Some gut bacteria have a different type of decarboxylase enzyme, which normally converts tyrosine into tyramine, but was found in this study to also convert levodopa into dopamine, before it can make it to the brain.

This is believed to be one of the reasons that some individuals need higher doses of carbidopa/levodopa to see an effect.

What if your probiotic/prebiotic drinks or pills are affecting how much levodopa makes it to your brain? (I’m being sarcastic, if you’re taking probiotics, don’t stop for this reason.)

Key takeaways from this study:

Gut bacteria can interfere with the effectiveness of levodopa drug treatment.

Tyrosine decarboxylase (TDC) genes are encoded in the genome of several bacterial species in the genera Lactobacillus and Enterococcus, converting levodopa into dopamine before it can cross the blood brain barrier.

TDC activity of the gut bacteria can interfere with levodopa/decarboxylase inhibitor availability, thus interfering with the treatment of PD patients.

Carbidopa does not inhibit bacterial TDC levodopa conversion (nor does  benserazide or methyldopa, other inhibitors sometimes used to help levodopa cross the blood brain barrier)

Levodopa conversion by gut bacterial TDC in the small intestine should be considered as a significant explanatory factor for the increased levodopa/carbidopa dosage regimen required in a subset of PD patients.

The researchers also noted that an abundance of Tyrosine did not prevent this unexpected levodopa decarboxylation, though it did result in a slightly slower conversion rate for levodopa.

In my opinion, this issue of gut bacteria impact on levodopa effectiveness has some practical significance for PD patients who see little improvement from the typical single pill dose of carbidopa/levodopa 10/25. Most PD patients dread increasing their dose of carbidopa/levodopa, because it implies progression of the disease. But what if a higher dose is simply needed to get enough levodopa to the brain?

What if years of levodopa treatment encourage growth in the number of TDC bacteria in your gut?