The microbes in our guts may interfere with medication – by eating it.
Harvard researchers writing in Science describe one of the first clear-cut examples of the microbiome impeding a drug's progress through the body by exposing the bacteria responsible for weakening the medication for Parkinson's disease (levodopa, or L-dopa), Enterococcus faecalis.
Our gut (or microbiome) is a complex ecosystem of microbial life (bacteria, viruses, fungi, etcetera) and scientific research is only starting to discover just how crucial it is to our mental and physical health. Some experts even go so far as to call it our "second brain".
These microbes play an important role in the break down of foods like fiber, which the human body cannot digest by itself. Unfortunately, there may be an unintended side effect and that is that the microbes can eat up medications too.
"Maybe the drug is not going to reach its target in the body, maybe it's going to be toxic all of a sudden, maybe it's going to be less helpful," first-author Vayu Maini Rekdal, a graduate student in the lab of Professor Emily Balskus, said in a statement.
One of those drugs is L-dopa, a treatment for the neurological condition Parkinson's, which causes patients to experience tremors, muscle rigidity, and difficulty balancing. More than 1 percent of over-60s are affected by the disease and L-dopa helps relieve symptoms by delivering dopamine to the brain.
The problem is that just 1 to 5 percent of the drug actually makes it to its intended target. (The exact amount varies from person to person.) Doctors prescribe it with carbidopa – which helps block unwanted L-dopa metabolism – but even then, more than half of L-dopa may fail to reach the brain. Rekdal thought microbes could be to blame.
Referencing the Human Genome Project, Rekdal and his team identified E. faecalis as a potential culprit. Lab testing confirmed it – E. faecalis was the only strain of bacteria to eat all the L-dopa every time, converting it to dopamine in the gut. This, the researchers say, is the first piece of strong evidence to connect the bacteria and its enzyme (PLP-dependent tyrosine decarboxylase, or TyrDC) to L-dopa metabolism.
But that's not all. While it seems carbidopa does little to prevent L-dopa metabolism, the researchers found something they think might without killing the bacteria. Instead of targeting (and destroying) E. faecalis, the molecule they have identified inhibits the enzyme and blocks the metabolic process. It's a possible foundation for a new – and more effective – Parkinson's treatment, they say.
The team also identified a bacteria involved in the second stage of the L-dopa metabolism process, Eggerthella lenta, which converts the dopamine into meta-tyramine. This meta-tyramine compound may be at least partly responsible for some of the negative side effects of Parkinson's treatment, but more research needs to be done to confirm this.
"All of this suggests that gut microbes may contribute to the dramatic variability that is observed in side effects and efficacy between different patients taking L-dopa," said Balkus.
And that might just be the start. If our microbiome can interfere with L-dopa, it's possible other strains of gut bacteria are affecting other types of medication.