A Predictive Computational Platform for Gut Microbiome Precision Medicine

Project SummaryAbstract The human gut microbiome has recently become a primary focus of therapeutic researchThis trend has been driven by a growing understanding of the intimate ties between the gut microbiome and various diseasesas well as interactions with different types of xenobiotics such as drugsSpecificallyevidence for the role of the gut microbiome as a determining factor in drug pharmacokinetics and therapeutics response has exponentially expandedThe pharmaceutical industry has become increasingly interested in the use of microbiome therapeutics that target and manipulate the gut microbiota to improve health conditions or prevent treat diseasesA major challengehoweveris the high variability of the gut microbiome composition across individualsLeading pharmaceutical researchers have begun to recognize that interindividual variations should be accounted for in attempts to develop personalized medicineHoweverdespite extensive progress in gut microbiome researchno current effort had been able to leverage personalizedomicsdata to explore the dynamics of gut microbiome in interacting with therapeuticsThis Phase I proposal targets an essential need at the intersection of two recent research initiatives announced by the White Housenamely the Precision Medicine Initiativeand the National Microbiome InitiativeThis project seeks to develop a predictive computational platform by integrating novel state of the art computational techniques and modeling approachesBy simulating the personalizedmulti scale dynamics of the gut microbiome in interaction with therapeuticsnew information can be leveraged to improve the effectiveness of drug design and developmentWe will employ complex systems approachescombined with computational biology techniquesto explicitly model the individual components of the complex network of gut microbiota as well as the rules governing their behaviore ginteractionsand predict systems level emergent behavior of the whole systemThis multi scale platform will be validated using targeted in vitro experiments and in vivo studiesThe outcome of this Phase I project will be a proof of concept of an integratedmulti scale computational platform for predicting the functional dynamics of gut microbiome in the context of pharmacomicrobiomicsi einteractions of the gut microbiome with therapeuticsThis in silico platform would reduce the cost and timeframe of drug development by reducing the need for iterative pre clinical experiments and better directing clinical trialswhile increasing the effectiveness of the therapeutics themselvesMoreoverthis platform can help increase the safety of pharmaceuticals by evaluating the mechanisms of toxicity as they may differ from individual to individualAs a resultthe pharmaceutical industry as well as academic researchers in the gut microbiome and precision medicine fields would benefit from the successful outcome of this project andin additionthis platform could eventually become an essential tool in personalizing the prescription of drug types and doses for specific therapeutics Project Narrative Individual variations in drug efficacy and toxicity is a major health and economic issueThis project aims to increase the effectiveness of drug development through the development of a novelpersonalized computational platform for predicting individual specific response of the gut microbiome to various drugs