Developing a Molecular Roadmap of Drug-Food Interactions

Recent research has demonstrated that consumption of food -especially fruits and vegetables- can alter the effects of drugs by interfering either with their pharmacokinetic or pharmacodynamic processes. Despite the recognition of such drug-food associations as an important element for successful therapeutic interventions, a systematic approach for identifying, predicting and preventing potential interactions between food and marketed or novel drugs is not yet available. The overall objective of this work was to sketch a comprehensive picture of the interference of ∼ 4,000 dietary components present in ∼1800 plant-based foods with the pharmacokinetics and pharmacodynamics processes of medicine, with the purpose of elucidating the molecular mechanisms involved. By employing a systems chemical biology approach that integrates data from the scientific literature and online databases, we gained a global view of the associations between diet and dietary molecules with drug targets, metabolic enzymes, drug transporters and carriers currently deposited in DrugBank. Moreover, we identified disease areas and drug targets that are most prone to the negative effects of drug-food interactions, showcasing a platform for making recommendations in relation to foods that should be avoided under certain medications. Lastly, by investigating the correlation of gene expression signatures of foods and drugs we were able to generate a completely novel drug-diet interactome map.现有研究表明，食用食物——尤其是水果与蔬菜——可通过干扰药物的药代动力学（pharmacokinetics）或药效动力学（pharmacodynamics）过程，改变药物的作用效果。尽管学界已认识到此类药物-食物相互作用是保障治疗干预成功的关键要素之一，但目前仍缺乏一套可用于识别、预测并防范食物与上市药物或新型药物间潜在相互作用的系统性方法。本研究的总体目标是系统梳理约1800种植物源性食物中含有的约4000种膳食成分对药物药代动力学及药效动力学过程的干扰情况，以期阐明其中涉及的分子机制。本研究采用整合了科学文献与在线数据库数据的系统化学生物学方法，全面解析了膳食及膳食分子与当前收录于DrugBank数据库中的药物靶点、代谢酶、药物转运体及载体蛋白之间的关联。此外，本研究还识别出最易受药物-食物相互作用负面影响的疾病领域与药物靶点，搭建了可针对特定用药场景给出需规避食物建议的分析平台。最后，本研究通过分析食物与药物的基因表达特征相关性，成功构建了全新的药物-膳食相互作用组图谱。