Understanding the potential of modulating Host-Microbiome-Glycan interactions (“the triangle of sweetness”) to tackle non-communicable diseases

ongoing

Glycans, namely human milk oligosaccharides (HMOs), play crucial roles in the functions of the gut, metabolism, and immunity. While HMOs are vital in infant development and exhibit bioactive properties in adults, it is required to analyze and decode their functions in depth. The current joint project by Inbiose and Utrecht University aims to identify >5 novel glycosyltransferase enzymes, produce >14 previously inaccessible HMOs, test glycan-microbe interactions in an ex vivo simulated gut microenvironment (SiFR® technology), decode direct and indirect effects of HMOs on the gut barrier in an in vitro cell model, and integrate the host-microbe-glycan interplay (“the triangle of sweetness”) in a human-microbial crosstalk (HuMiX) model. Thanks to powerful statistical methods, machine learning, and natural language processing techniques, we envision a thorough understanding about glycan structure-function relationship and predict their potential applications with stratifications based on gender, diet, and health conditions. We expect to validate at least one HMO alleviating impact of inflammation under two diets that is ready for a clinical trial. Cutting-edge Omics methods and data analysis pipelines will allow us to understand better the host-microbe-glycan triangle, and will provide both a wealth of research data and an expanded range of HMOs as research tools and potential therapeutics and/or preventives in human non-communicable diseases and food-related health conditions. Our unique consortium capacities and a wealth of experience in glycoengineering, biosynthesis, bioinformatics, and noncommunicable chronic disease targeting will enable us to achieve the project goals. The project will create additional opportunities for Inbiose and UU in the further exploration and commercialisation of HMOs. We fully expect InteractHoMiG to be a milestone project for glycobiology research and prebiotic/probiotic/postbiotic/synbiotic R&D within the EU and worldwide.