2019 International Biocodex Microbiota Foundation grant: Prof. Emily Balskus rewarded for her research on inhibiting the gut microbiota's degradation of Parkinson's disease medication
CAMBRIDGE, Mass., Sept. 10, 2019 /PRNewswire/ -- The International Biocodex Microbiota Foundation has awarded its 2019 grant to Emily Balskus, Professor of Chemistry and Chemical Biology at Harvard University. "I am extremely honored to be chosen to receive this grant and am very grateful to the Biocodex Microbiota Foundation for supporting my research", Prof. Balskus immediately reacted.
"Gut microbiota and drug metabolism", the topic of the 2019 call for projects
The topic chosen by the Biocodex Microbiota Foundation for its international call for projects this year was "Gut microbiota and drug metabolism", a subject that falls precisely within the area of research addressed by Prof. Balskus and her team. As she puts it, "Humans are colonized by trillions of microorganisms that exert a profound influence on health and disease. The unique chemical capabilities of the human microbiome play an important role in these processes, but the microbial pathways and enzymes involved in these metabolic interactions are largely unknown. For example, the human gut microbiota can interact with small molecule drugs, altering their chemical structures and thereby affecting their activity and toxicity. We propose that by elucidating the molecular basis for crucial microbial activities and developing strategies to inhibit them in complex communities, we will gain insights into the mechanisms that underlie the gut microbiota's influence on the biology of its host. This might reveal opportunities for new therapies."
Gut microbes metabolize Parkinson's medication
The particular area where Emily Balskus and her team are deploying this strategy? Parkinson's disease, a debilitating neurological condition that affects more than 1% of the global population aged 60 and over. Explaining her interest in this new line of research, Prof. Balskus recalled: "We started studying the microbiota's influence on Parkinson's disease treatment when a new graduate student, Vayu Maini Rekdal, joined the lab. He wanted to start a new project focused on drug metabolism. We checked the available literature and quickly became excited since there was strong evidence for interaction between the gut microbiota and Parkinson's treatment, but no details were known about which microbes, genes, and enzymes might be responsible."
As Prof. Balskus explains, the primary medication used to treat Parkinson's disease is Levodopa (L-dopa), which replaces the dopamine that impaired brain cells are no longer producing. The gut microbiota is able to metabolize L-dopa within the gut, which thereby diminishes the drug's availability to the brain and hence the efficacy of the treatment. Moreover, when L-dopa is transformed into dopamine outside the brain by the gut microbiota, the compounds formed can cause side effects, including cardiac arrhythmias and severe gastrointestinal disorders.
In a recent study, Prof. Balskus' team identified for the first time the species of bacteria that are involved in L-dopa metabolism. This work (since published in Science1) drew the attention of the independent International Scientific Committee of the Biocodex Microbiota Foundation, in charge of reviewing the proposals: "Beyond the lab's considerable experience in the field, it's their very strong preliminary data that drove us to select Prof. Balskus' project," commented Prof. Harry Sokol, gastroenterologist at the Saint Antoine Hospital in Paris, France, and Chair of the Committee.
Developing strategies to stop the gut microbiota degrading medication
The €200,000 grant will support Prof. Balskus' team in the next stages of their research: "In our preliminary work, we identified an inhibitor that can stop gut microbial L-dopa metabolism in whole cells and complex patient microbiotas. These discoveries have opened the way to exciting new perspectives. Thanks to the Biocodex Microbiota Foundation grant, we can look at optimizing the inhibitor of L-dopa metabolism using chemical synthesis, and then test its activity in animals, including a model of Parkinson's disease."
The research team hopes thereby to demonstrate that it is possible to manipulate and control unwanted gut microbial drug metabolism in a complex environment. "Within the next 1 or 2 years, we hope to identify optimized inhibitors of gut bacterial L-dopa metabolism," Prof. Balskus says. "And we are already involved in a collaboration to further test the hypothesis that gut microbial L-dopa metabolism is correlated with dosing and response to the drug," she adds.
An innovative new direction for therapeutics
More broadly, this work should further demonstrate the feasibility of improving drug efficacy by manipulating gut microbial metabolism, an innovative new direction for therapeutics. "The timeline for developing drugs in humans is hard to predict,' Prof. Balskus comments, 'but modulating the gut microbiota is an extremely promising strategy. One example of how this general idea has already helped patients is in the context of fecal microbiota transplants and recurrent Clostridium difficile infections. What is different about our approach is that we would like to use small molecules to manipulate functions in a patient's own native community. This more precise method may preserve the beneficial functions of the microbiota. It's an approach that could be aided by diagnostics that indicate whether a patient has a specific kind of activity in their gut community. Overall, we think that the gut microbiota may provide a wealth of potential new targets for drug development."
This is a view shared by Prof. Sokol : "Looking forward, we hope that Prof. Balskus' findings will highlight the value of taking into account the gut microbiota when treating a patient with Parkinson's disease, either to modulate the efficacy of the treatment or to decide whether or not this treatment is to be given," he concludes.
About Biocodex Microbiota Foundation
About Prof. Emily Balskus
1 Maini Rekdal V, Bess EN, Bisanz JE, Turnbaugh PJ, Balskus EP. Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism. Science. 2019 Jun 14;364(6445). doi: 10.1126/science.aau6323.
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