Following on from an incredible Yale University study examining the metabolic relationship between common medications and different gut bacterial species, a new study has offered the first rigorous description of how a single bacterial species can specifically disrupt the efficacy of a drug used to treat Parkinson's disease.
For decades Levodopa (L-dopa) has been the only effective drug treatment for Parkinson's disease sufferers. However, the efficacy of the drug is known to vary dramatically from patient to patient. Clinicians have long been aware that some of these variances can be explained by certain enzymes that metabolize the drug before it can travel to the brain, and secondary medications have been developed to help stifle this unwanted metabolism. But still, major variations in efficacy from person to person remain.
It has previously been found that heavy doses of broad-spectrum antibiotics can enhance a patient's response to L-dopa, implying certain gut bacteria could be responsible for metabolizing the drug. Investigating this hypothesis, a team of researchers from Harvard University and the University of California San Francisco set out to discover whether a single bacterial species could be responsible.
The researchers first hunted down what specific gut bacteria species had the ability to produce enzymes known to metabolize amino acids similar to L-dopa. Several species fit the bill, but one bacteria metabolized L-dopa consistently across every strain tested: Enterococcus faecalis (E. faecalis).
The researchers discovered that E. faecalis effectively converts L-dopa into dopamine before the drug can reach the brain. Following that, it was discovered that a molecule called tyrosine can block the enzyme produced by E. faecalis that metabolizes L-dopa.
"The molecule turns off this unwanted bacterial metabolism without killing the bacteria; it's just targeting a non-essential enzyme," explains first author on the new research, Maini Rekdal.
While this mechanism explains how L-dopa's pathway to the brain can be disrupted, further study revealed a second microbial process that may underpin many negative side effects suffered by some Parkinson's patients when taking the drug.
The researchers discovered another bacterial species, called Eggerthella lenta (E. lenta), takes the excess dopamine created and converts it into meta-tyramine. This particular microbial action surprised the researchers, and it's hypothesized this secondary mechanism could modulate many side effects commonly known to relate to L-dopa.
"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," says Emily Balkus, corresponding author on the new study.
One of the most compelling, and burgeoning, areas in medical research today is the influence of our gut microbiome on a whole host of mechanisms in our body. A Yale University study just last week catalogued how 76 kinds of gut bacteria can negatively affect 176 commonly prescribed medicines. Ultimately this new research paints the most complete picture to date of how a specific bacterial species can disrupt the metabolism of a commonly used drug.
The striking study offers a new insight into why medicines do not work the same way in every person, and better understanding these mechanisms may suggest ways to significantly improve the efficacy drugs we have already developed, instead of producing entirely new ones.
The new research was published in the journal Science.
Source: Harvard University
