The intestinal microorganisms of a person reaching the number of shellfish are the same as the treasure house of enzymes. Intestinal microorganisms directly modify and metabolize food, drugs, and toxins that people ingest. Intestinal microorganisms are primarily beneficial, but they also occasionally alter the bioavailability and efficacy of drugs.
It has been found that the intestinal microbes have been shown to deteriorate the performance of levodopa (L-dopa or Eldopa), one of the most important medicines for Parkinson's disease.
Harvard Medical School researchers reported in a paper published in the journal Science on Thursday that "intestinal microbes are two-step intestinal microbial enzymes that break down levodopa, a drug for Parkinson's disease, into dopamine and then transform it into meta-tyramine I have identified the route. " In other words, intestinal microorganisms eat the most important treatment for Parkinson's disease, and the treatment effect is greatly reduced.
Globally, 10 million people suffer from Parkinson's disease, and levodopa has been used as an important remedy for over 50 years. When dopamine is depleted in the brain of patients with Parkinson's disease, they cause movement disorders such as tremors, stiffness, and slow motion.
Levodopa, a precursor of dopamine, is a drug commonly taken orally. Levodopa is absorbed into the small intestine, crossing the blood-brain barrier into the brain, and converting it into dopamine in the brain. Dopamine supplementation alleviates the symptoms of Parkinson's disease but does not prevent the progression of Parkinson's disease.
"The drug may not reach the target in the body, it may suddenly become toxic, or it may help," says Emily P. Balskus, a professor at the Maini Rekdal graduate student in the lab. It may be less. "
The researchers focused on levodopa, the first line of treatment for Parkinson's disease, as the first study of how intestinal microbes could interfere with the intended route of medicine to pass through the body. This is because levodopa delivers dopamine to the brain to relieve Parkinson's disease, but only about 1 to 5% actually reach the brain.
The effect of Parkinson's disease treatment was 1 ~ 5%
Since the introduction of levodopa in the late 1960s, researchers have learned that the body's enzymes can break down the visceral levodopa and prevent drugs from reaching the brain. So the pharmaceutical industry has introduced a new drug, carbidopa, to block unwanted levodopa metabolism. When taken together, the treatment seemed to work.
Even so, there are many metabolites that are not explained, and they are very variable for each person. If levodopa is turned into dopamine outside the brain, it can cause severe gastrointestinal disturbances and side effects such as cardiac arrhythmia. If there are fewer drugs reaching the brain, patients are likely to exacerbate these side effects because they need to take more medication.
Leekdal suspects that there may be microorganisms behind the disappearance of the levodopa. Since previous studies have shown that antibiotics improve the function of patients' levodopa, scientists speculated that bacteria might be the cause. But no one knows which bacteria play such a role, and how and why the bacteria eat them.
The team used the Human Microbiome Project to track bacterial DNA to find out what intestinal microbes were the killer. As a result of the project, only one variant, E. faecalis, was found to eat all levodopa every time.
However, human enzymes convert levodopa to dopamine in the intestine, and the carbidopa is designed to stop this phenomenon. Then the researchers wondered why carbidopa did not affect the enzyme Enterococcus faecalis.
But the cause may not be important. The researchers have already discovered molecules that can inhibit bacterial enzymes.
"This molecule does not kill the bacteria and blocks the metabolism of unwanted bacteria," said Lekdal. This is only aimed at non-essential enzymes. "
The researchers hope that similar compounds could provide a starting point for new drug development to improve levodopa therapy in Parkinson's patients.
The role of intestinal microorganisms
The research team did not stop there. He further pushed to solve the second stage of levodopa microbial metabolism. Finally, after Enterococcus faecalis switched levodopa to dopamine, a second organism discovered a mechanism to convert dopamine to another compound, meta-tyramine.
A byproduct of meta-tyramine may contribute to some harmful levodopa side effects. Further research is needed, but why would bacteria eat brain-related dopamine? What else can intestinal microorganisms do? And does this chemistry affect our health?
All this suggests that the microbes of the intestines can contribute to dramatic changes, whether side effects or efficacy, among other patients taking levodopa, Professor Valkscu said.
Importantly, microbial interference may not be limited to levotopa and Parkinson's disease. The research is expected to serve as an important starting point for finding out exactly who is in a person's body, what they can do, and how they affect their health, both good and bad.