Periodic Reporting for period 3 - BugTheDrug (Predicting the effects of gut microbiota and diet on an individual’s drug response and safety)
Berichtszeitraum: 2020-08-01 bis 2022-01-31
- Researchers will develop a novel, innovative computer model consisting of a highly curated database of human, microbial, dietary, and drug metabolism information and a software that allows the prediction of a person's drug response based on customizable database queries and input data (such as diet, genetic make-up, and gut microbe composition).
- Researchers will use the computer model to predict metabolites in the blood that can identify colon cancer patients that will have severe side-effects to certain chemotherapy and validate these metabolites in a small group of colon cancer patients.
- Researchers will use the computer model to predict specific food items for Parkinson's disease patients treated with levodopa, a drug is commonly used to reduce the motor symptoms of Parkinson's disease patients, to reduce treatment side effects. These predictions will be tested in collaboration with neurologists and nutritionists in a small number of Parkinson's patient. The study results will help to improve the computer model further.
The content of the VMH database is continuously maintained and expanded within this research project. For instance, researchers have recently added a detailed biochemical description of gut microbial bile acid metabolism, which may play a role in many human diseases, including Parkinson's disease.
Researchers are now expanding the information included in the VMH with human and microbial metabolism of over 100 commonly prescribed drugs. This information is again collected from peer-reviewed scientific studies and requires the detailed investigation of gut microbial genomes to identify a microbe's potential to modify drugs and their derivatives. This step is crucial as experimental data for many gut microbes are not available, despite recent advances in understanding the role of gut microbes in human drug metabolism.
Researchers are developing novel computational methods to enable the direct analysis of gut microbe data as well as nutritional and physiological information. These computer methods will be directly connected with the VMH database to allow for cross-reference of computer simulations and currently biochemical knowledge. In addition to including microbial and nutritional information in the computer models, the new computer methods will enable to simulate human and microbial metabolism as well as pharmacokinetic properties of one or more drugs.
Microbial drug metabolism remains understudied despite recent discoveries in microbiology. Subsequently, the genomic annotation and the detailed description of drug metabolism that has been carried out during the first 18 months will provide valuable insight into microbial capabilities to modulate commonly prescribed drugs. Once, publically made available, this resource will enable researchers to estimate the influence of microbial drug metabolism on an individual's drug response and allow other researchers to formulate novel, experimentally testable hypotheses.
The combination of biochemistry-based computer models and pharmacokinetic models has been described in the scientific literature with a few examples. However, the computer models generated within this ERC project will go beyond these published efforts both on the level of captured biochemistry, most notably the microbial metabolism, but also with the extent to a variety of the drugs that will be covered.
Consequently, the computer model will be used for hitherto unpreceded applications, such as the prediction of metabolites that could help to identify colon cancer patients that would develop severe side-effects to certain chemotherapy drugs. Similarly, the prediction of dietary supplementations for Parkinson's disease patients based on their gut microbial make-up. If the anticipated proof-of-concept study is successful, this application may provide an improved, personalised treatment strategy for Parkinson's disease patients.