Some drugs, once inserted in the human body, do not have the desired effect, or at least not at a sufficient level, because they can be degraded by the microbes present in the body itself. A concrete example comes from the microorganisms of the intestinal microbiome: the latter can interfere with the path that the drugs ingested orally should have through the body. Microbes degrade the drug and interfere with its action.
Further evidence came from a new study by researchers at Harvard University published in Science. The same microbial metabolism that can be very useful, especially with regard to digestion, can also be harmful, as reported by Maini Rekdal, a student of Professor Emily Balskus and the first author of the study. Intestinal microbes can indeed “chew” drugs and this can have dangerous side effects because the drug itself can eventually be toxic, not just less useful.
Researchers are concentrating on levodopa (L-dopa), one of the primary treatments for Parkinson’s disease, identifying which are the bacteria responsible for its degradation. Levodopa, once ingested, must transport dopamine into the brain to alleviate the symptoms of the disease but only 1-5% of this drug can reach the brain. This is because there are various enzymes in the body that already break it down in the intestine. The researchers then introduced another drug, carbidopa, to block this undesirable metabolism that converts levodopa into dopamine already in the intestine but also in this case, although in a variable way from person to person, the body’s metabolism began to degrade also this second drug causing serious and bothersome side effects in many patients.
Scientists have hypothesized that intestinal microbes degrade levodopa but no one was able to identify what they were. Rekdal has succeeded that the bacterium Enterococcus faecalis eats all of the levodopa. The researcher, together with his colleagues, has also already discovered a molecule that inhibits the enzyme that the bacterium uses to degrade the drug. This molecule does not kill bacteria but only interferes with its metabolism by targeting its non-essential enzyme.
The same researchers also discovered a second microorganism, the slow Eggerthella, present in the intestine that acts after the E. faecalis has acted. After the latter transforms the drug into dopamine already in the intestine, this second microorganism performs a new conversion transforming dopamine into meta-tyramine. However, once the enzyme of the slow Eggerthella is inhibited, this second conversion can no longer take place because the drug is no longer transformed into dopamine.