Gut-on-chip Utilization for Therapeutic design: Microbiome-epithelium interactions Model And Predictions

The gut epithelium is a dynamic interface where microbial metabolism, mucus structure, and mechanical cues jointly determine barrier function and disease susceptibility. Conventional approaches—such as fecal omics, animal models, and static Transwells—either lack human relevance or the spatiotemporal control required for predictive modeling and therapeutic design. Gut-on-chip devices have recently emerged as powerful tools to bridge this gap, reproducing key features of the human intestine, including oxygen gradients, peristaltic-like flow, mucus layers, and co-culture with anaerobic microbial consortia. These systems enable causal experiments under controlled regimes, yet their use has remained largely descriptive, and no predictive computational framework exists to generalize experimental results or guide rational intervention strategies.GUT-MicroMaP addresses this gap by developing and validating the first rigorously calibrated, spatially explicit mathematical model of microbiome–epithelium interactions in gut-on-chip systems. The project will integrate high-resolution spatial multi-omics data from the 3D’omics consortium with hybrid PDE–ABM–CFD modeling to create a digital twin of the gut environment. This model will capture microbial motility, adhesion, and biofilm dynamics under metabolites and mucus conditions, and will be iteratively refined through Bayesian calibration and sensitivity analysis. Once validated, it will serve as an in-silico platform to design microbiome-directed therapeutic strategies—including prebiotics, probiotics, and phage therapies—optimizing barrier integrity while suppressing pathogens. Therapeutic insights will integrate sex/gender variability in gut physiology and immunity, ensuring broader relevance and equity. By merging spatial omics with advanced modeling, GUT-MicroMaP will deliver a transformative predictive framework for gut health, opening new avenues for rational therapeutic design in microbiome research.