GlycanTrigger – Glycans as Master Triggers of Health to Intestinal Inflammation Transition
Chronic inflammation, a prominent feature in prevalent conditions like Inflammatory Bowel Disease (IBD), indicates a prolonged and misguided immune system response that significantly impacts the quality of life of many individuals. In the case of IBD, encompassing conditions such as Crohn’s disease (CD) and ulcerative colitis, the repercussions of persistent inflammation within the digestive tract are far-reaching, manifesting as a spectrum of debilitating symptoms. Unravelling the underlying mechanisms of chronic inflammation is crucial for developing widespread and effective interventions to reduce the burden on those affected by common and challenging health issues.
GlycanTrigger, a six-year project funded by the European Union within the Horizon Europe Research and Innovation Actions, aims, through a comprehensive and innovative approach, to explore how changes in the gut glycome can trigger intestinal inflammation. With a dual focus on both local and systemic impacts, GlycanTrigger seeks to elucidate how altered glycosylation disrupts host-microbiome interactions and promotes the production of antimicrobial antibodies. Focusing on glycosylation changes within the gut mucosa, this project introduces the concept of glycan mimicry as a primary instigator in the transition from health-to-chronic inflammation. Changes in complex branched N-glycans have been identified as regulators of IBD immunopathogenesis, suggesting that alterations in the gut glycocalyx disrupt the local mechanisms and trigger systemic responses. Moreover, recent discoveries indicate that changes in glycosylation can be detected in the serum years before CD diagnosis, correlating with increased levels of pathogenic antimicrobial antibodies (ASCA). The long-term goal is to identify a novel checkpoint regulating the transition to chronic inflammation, providing breakthrough insights into the health to chronic inflammation transition, offering new perspectives on CD development, and providing tools for CD prediction and prevention to potentially improve the well-being of at-risk individuals.
The EU has awarded the GlycanTrigger project with 6.8 million EUR. The Consortium starts its work in January 2023 and consists of 9 organizations from 7 different European and non-European countries: i3S – Instituto de Investigação e Inovação em Saúde from the University of Porto (Portugal), LUMC – Leiden University Medical Center (The Netherlands), Sorbonne Université (France), Charite – Universitaetsmedizin Berlin (Germany), GLSMED Learning Health SA (Portugal), Icahn School of Medicine at Mount Sinai (USA), EFCCA – European Federation of Crohn’s and Ulcerative Colitis Associations (Belgium), SPI – Sociedade Portuguesa de Inovação (Portugal), Ludger Limited (UK).