GLYCANS AS MASTER TRIGGERS OF HEALTH TO INTESTINAL INFLAMMATION TRANSITION

Project Information

GlycanTrigger

Grant agreement ID: 101093997

DOI

10.3030/101093997

EC signature date 5 December 2022

Start date 1 January 2023

End date 31 December 2028

Funded under

• Health

Total cost

€ 6 771 571,00

EU contribution

€ 6 771 571,00

Coordinated by

I3S - INSTITUTO DE INVESTIGACAO E INOVACAO EM SAUDE DA UNIVERSIDADE DO PORTO
Portugal

Periodic Reporting for period 2 - GlycanTrigger (GLYCANS AS MASTER TRIGGERS OF HEALTH TO INTESTINAL INFLAMMATION TRANSITION)

Reporting period: 2024-07-01 to 2025-12-31

Summary of the context and overall objectives of the project

GlycanTrigger is a project funded by the European Union, within the Horizon Europe Research and Innovation Actions (RIA). The long-term goal of GlycanTrigger is to unlock a new checkpoint that regulates health to chronic inflammation transition by proposing mucosa glycans modifications as a master switch towards the early perturbation of host-microbial interactions and the consequent activation of both innate and humoral immune systems. Ultimately, we want to intercept or revert this master switch and thereby exploit/analyse whether this constitutes an opportunity to prevent the development of chronic inflammation in at-risk individuals.
Chronic inflammation is the underlying cause of numerous diseases, including Crohn's disease (CD), which may have a preclinical phase with immunological changes occurring before symptoms manifest. To improve disease prediction and prevention, our innovative approach seeks to understand the health-to-intestinal inflammation transition using CD as a disease model. The GlycanTrigger project will investigate when, why and how changes in glycosylation at the surface of the gut mucosa, constitute an early trigger of the health-to-inflammation transition. We will address how changes in glycosylation of the gut mucosa act as a primary event that dysregulates not only local mechanisms, but also systemic mechanisms associated with health to inflammation transition. Although high-risk/high-gain, our project is based on appropriate and long-standing expertise and fundamental biological principles that the consortium has helped establish and is thus likely to lead to (i) breakthrough biomedical concepts in the driving factors that trigger the health to chronic inflammation transition and to (ii) novel predictive tools for early detection of at-risk individuals to develop chronic inflammation, as well as to (iii) a novel intervention strategy that will be tested for disease prevention. In the longer term, the results of GlycanTrigger will improve health literacy through better-informed management of health status, diet and life-style to maintain a healthy gut.
Our strategy for understanding the transition from health to gut inflammation is comprehensive and includes the impact of mucosa glycans on local and systemic mechanisms.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In GlycanTrigger, we are investigating when, why and how changes in gut glycome trigger health to chronic inflammation transition.

Studies in both preclinical models and human patients have revealed that changes in gut mucosa glycome are associated with amplified anti-glycan immunity. Importantly, mechanisms observed in human Crohn’s disease mirror those seen in mouse models, linking mucosa glycans changes to disease severity. Preclinical studies further demonstrated that changes in mucosa glycans increases susceptibility to colitis.

A major milestone for the project has been the successful setup and initiation of the clinical study testing prophylactic glycan supplementation to modulate mucosal glycosylation and immune responses. Preclinical results indicate that glycan supplementation restores immune balance and protects against severe forms of colitis, supporting its potential therapeutic application.

Finally, across multiple cohorts, predictive glycomic models have been developed that reliably distinguish disease from healthy states, demonstrating high reproducibility and identifying glycans with potential as early biomarkers for CD. Collectively, these achievements represent substantial progress toward understanding the mechanisms driving IBD and translating these insights into clinical interventions.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

We have provided compelling preliminary evidence supporting that changes in the gut mucosa glycome composition are occurring in the transition from health to inflammation in CD. We demonstrated that these changes impact immune responses and gut health significantly. Additionally, our research identified potential therapeutic strategies, including glycan supplementation and microbiome interventions, which could revolutionize CD treatment and prevention. The findings also highlight the importance of early detection and personalized medicine in managing CD. Moving forward, continued research, strategic partnerships, and supportive frameworks will be crucial to realizing the full potential of these results.