InteractHoMiG
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UNDERSTANDING THE POTENTIAL OF MODULATING HOST-MICROBIOME-GLYCAN INTERACTIONS (“THE TRIANGLE OF SWEETNESS”) TO TACKLE NON-COMMUNICABLE DISEASES (INTERACTHoMiG)
This project has recieved funding from the European Union’s Horizon Research and Innovation programme under the HORIZON-EIC (HORIZON-EIC-2023-PATHFINDERCHALLENGES-01) grant agreement No. 101161110
Project description
First year key results
Over the last year, several tasks have been successfully executed, resulting in significant progress and some achievements were obtained.
- We expanded our glycosyltransferase library by more than 200 enzymes and produced the first set of glycans for initial gut barrier function screening using a newly optimized Caco-2 intestinal epithelial model.
- In addition, we developed a microbial strain capable of producing a complex mixture of HMOs mimicking human milk composition, advancing our disruptive innovation in the field of infant formula and dietary supplements.
- A panel of 20 human milk oligosaccharides was screened using the optimized intestinal epithelial Caco-2 cell model. Barrier integrity was assessed by TEER (transepithelial electrical resistance) measurements, yielding promising results, particularly for several newly developed HMOs.
- In parallel, we conducted preparatory experiments to optimize microbial strains, exposure conditions and readouts for Caco-2 cells within the HuMiX 4.0 model, while also developing a high-throughput screening platform based on a Hollow-Fiber Membrane Gut-on-a-Chip model to investigate host-microbe-glycan interplay.
- For the Precision nutrition portfolio, the InteractHoMiG consortium contributed ideas to develop further and to implement the strategic plan by joining the steering committee and actively participating in working groups. Potential cross-project collaborations with other projects were identified and will be further explored in the near future. Details of the portfolio strategic plan are published in the Publications Office of the European Union website.
Initial project
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 Utrecht University and Inbiose aims to identify novel glycosyltransferase enzymes, produce previously inaccessible HMOs, test glycan-microbe interactions in an ex vivo simulated gut microenvironment, 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 Utrecht University and Inbiose 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.
The InteractHoMiG project work plan is divided into 10 WPs designed to maximise the use of time and resources to achieve the proposed objectives and summarised in the PERT chart.
WP1&2 will be dedicated to glycan library creation and synthesis.
WP3&4&5 will aim to characterize the host-glycan-gut microbiota interaction to generate a wealth of data on the effects of glycans.
WP6 will deal with deciphering the glycan structure-function relationships and prediction of their potential applications.
WP7 will be an in vivo validation of a selected glycan molecule in a rodent model.
WP8 encompasses the EIC Pathfinder Challenge portfolio activities are therefore will be dedicated to promoting awareness of the technologies developed in the InteractHoMiG project and disseminating results of the project across the scientific community and market stakeholders, to ensure their feedback and participation to the project outcomes and secure their collaboration for future development. The WP will also be dedicated exploiting project results. All activities will be coordinated within WP9, which will be dedicated to ensuring prompt implementation of project activities within the set deadlines and budget.
Finally, to promote the synergies of the projects and the impact of the precision nutrition program, WP10 will be dedicated for the portfolio activities, e.g. effective communications, standardization activities, discussing on common strategies, ….
Partners
News and events
Milestone is reached!
Proud to share that the InteractHoMiG team have reached an important milestone:
- 15 enzymes displaying specific branching activity on different substrate were identified in vitro.
- Two enzymes of the in vitro tested group were also tested in an engineered strain and showed detectable branched HMO production. This is a first proof-of-concept for in vivo synthesis of branched HMOs.
Stay tuned with us for the more branched HMOs in the future!
Huge thanks to the whole InteractHoMiG team and the strain engineering teams at Inbiose for making it happen! We are grateful for the support of the EIC Pathfinder and the collaborations in the Precision Nutrition portfolio.
On 10/11/2025, the periodic review meeting of the InteractHoMiG project took place with the Project Officer, together with Inbiose and Utrecht University. We are pleased to report a very positive outcome.
Both the European Innovation Council (EIC) and the expert monitors provided positive evaluations of the project’s progress and results to date.
We would like to express our sincere appreciation to Project Officer (Ioannis Manolidis), EIC Pathfinder Precision Nutrition Programme Manager (Ivan Stefanic) EIC Pathfinder Precision Nutrition Portfolio Officer (Danilo Pietretti) and two expert monitors: Alba Silipo & Joao Carlos Cruz de Sousa for their constructive feedback and continued support.