Mariam Malik ‘22
A drug is characterized as any substance that may alter one’s psychology or physiology. Depending on its purpose, each drug takes a different path once inside the body, but researchers at Harvard University have determined the role of the gut in interfering with a drug’s path and eventually, its effectiveness.
Professor Emily Blaskus and graduate student Vayu Maini Rekdal focused on Levodopa, commonly known as L-dopa. L-dopa is the primary drug used to treat Parkinson’s disease, a progressive disorder of the nervous system. The disease attacks dopamine-producing nerve cells causing movement issues. L-dopa provides dopamine to the brain to relieve some symptoms, but previous research has shown that only 1-5% of the drug actually reaches the brain. Because our gut contains billions of various bacteria, the objective of the study is to discover which bacteria, if any, cause a change in a drug’s pathway and purpose.
Furthermore, L-dopa also works because of Aromatic L-Amino Acid Decarboxylase (AADC), the enzyme that causes the drug to produce dopamine. Thus, the researchers used genome mining to help identify which gut microbes possessed the gene to code for an enzyme similar to AADC which binds to the amino acid, tyrosine. Enterococcus faecalis and Enterococcus faecium both showed activity, but E. Faecalis showed complete consumption of L-dopa across all strains that were tested. Both bacteria are AADC inhibitors, but researchers also went a step further and found that another organism, E. lenta, further metabolizes dopamine. This alteration could cause a plethora of side effects from administering L-dopa and subsequently producing dopamine.
The study offered insight into the role of the gut microbiome in pharmacokinetics ( the study of how a drug moves through the body) and pharmacodynamics ( the study of how a drug affects the body). The gut’s interference may not be limited to Parkinson’s disease and L-dopa, but could reveal more about how our gut impacts our health.
- V.M. Rekdal et al., Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism. Science 364, (2019). Doi: 10.1126/science.aau6323
- Image retrieved from: https://commons.wikimedia.org/wiki/File:Wild_garden_of_the_gut_bacteria_6.jpg