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

Introduction

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.

Project Overview

The current joint project by Inbiose and Utrecht University aims to:

1. Identify >5 novel glycosyltransferase enzymes.
2. Produce >14 previously inaccessible HMOs.
3. Test glycan-microbe interactions in an ex vivo simulated gut microenvironment (SiFR® technology).
4. Decode direct and indirect effects of HMOs on the gut barrier in an in vitro cell model.
5. Integrate the host-microbe-glycan interplay (“the triangle of sweetness”) in a human-microbial crosstalk (HuMiX) model.

Methodology

Thanks to powerful statistical methods, machine learning, and natural language processing techniques, we envision a thorough understanding of the glycan structure-function relationship. This will allow us to predict their potential applications with stratifications based on:

• Gender
• Diet
• Health conditions

Expected Outcomes

We expect to validate at least one HMO alleviating the 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 better understand the host-microbe-glycan triangle. This 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.

Consortium Strengths

Our unique consortium capacities and a wealth of experience in:

• Glycoengineering
• Biosynthesis
• Bioinformatics
• Noncommunicable chronic disease targeting

will enable us to achieve the project goals.

Future Opportunities

The project will create additional opportunities for Inbiose and UU in the further exploration and commercialization 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.