About

About GlycanTrigger project

GlycanTrigger is a project funded by the European Union within the Horizon Europe Research and Innovation Actions, bringing together 9 organisations from 6 different European countries and 1 non-European country (USA).

In GlycanTrigger, we will investigate when, why and how changes in gut glycome trigger health-to-chronic inflammation transition. The project started in January 2023 and will be developed for 6 years under the coordination of Instituto de Investigação e Inovação em Saúde (i3S) from the University of Porto, Portugal. The GlycanTrigger consortium includes representatives from medical universities and research centers, clinical centers, one biotechnology company, one consultancy company, and one European patients’ association.

Scope of the project

Which diseases and challenges are we addressing?

Inflammatory bowel disease (IBD) includes two main disorders, Crohn’s disease (CD) and ulcerative colitis (UC), that are characterised by uncontrolled inflammation of the gastrointestinal (GI) tract. According to epidemiological studies, the incidence of IBD is progressively increasing in recently industrialised areas and in young individuals in developed nations. In order to develop targeted interventions to stop the global spread of IBD, efforts must be focused on understanding the earlier events that take place before disease onset.

What is our hypothesis?

There is growing evidence of an IBD preclinical phase l, where the disease is initiated (before clinical symptoms) by interactions between the host and environmental risk factors in genetically susceptible individuals, and then progressively develops through different phases. Our hypothesis is that changes in the glycosylation of the gut mucosa act as a primary event that dysregulates local and systemic mechanisms, leading to the health-to-chronic inflammation transition.

How are we addressing the challenge?

We will study how changes in the glycans that protect our gut (called the glycocalyx) can perturb the interaction with gut bacteria (affecting host-microbiome interactions), leading to the activation of the immune system and to the development of auto-antibodies), that together culminate in health to intestinal inflammation transition . We will be looking at how this happens and why it is a problem, so that we can try to find ways to prevent or treat gut inflammation.

How will our results contribute to a solution?

Our results will contribute to a solution by providing breakthrough concepts in the health-to-chronic inflammation transition and novel predictive tools translated into novel-intervention strategies for disease prevention. By unlocking a new checkpoint that regulates the transition to chronic inflammation, we hope to improve disease prediction and prevention for patients with CD and potentially other diseases associated with chronic inflammation. A better understanding of the preclinical stage could improve therapeutics, disease prediction and prevention, as well as a better understanding of disease pathogenesis.

Objectives

GlycanTrigger wants to find a way to intercept chronic inflammation by studying how changes in the composition of glycans that attach to the lining of the gut impact the initiation of the inflammatory process. The project’s long-term goal is to understand the contribution of gut mucosa glycome in health to intestinal inflammation transition aiming to figure out how to turn off this process by developing novel preventive intervention strategies

Objective 1

Define the gut glycome map during the transition from health to chronic inflammation.

Objective 2

Investigate how changes in gut glycocalyx impact microbial and immunological dynamics, leading to dysbiosis and inflammation.

Objective 3

Explore how changes in gut mucosa glycans activate both innate and humoral immune responses

Objective 4

Test novel therapeutic interventions in preventing the shift from health to inflammation.

Objective 5

Maximize the societal impact through targeted dissemination, communication, and engagement with relevant stakeholders, towards improving health literacy and empowering patients for disease prevention.

Consortium

Instituto de Investigação e Inovação em Saúde (i3S) merges three institutes and researchers from several schools of the University of Porto, thus consolidating an extensive collaboration between all institutions spanning many years. i3S aims to face and overcome the most relevant health challenges society faces today, such as ageing, infectious diseases, cancer, regenerative medicine, and neurodegenerative diseases.

i3S is the project coordinator of GlycanTrigger. Furthermore, i3S is in charge of the project management, ethics, data management, gender equality, intellectual property rights, and in the consortium meetings organisation.

www.i3s.up.pt

Leiden University Medical Center (LUMC), located in Leiden, Netherlands, is the university hospital affiliated with Leiden University, of which it forms the medical faculty. LUMC is a modern university medical center for research, education, and patient care. Its research practice ranges from pure fundamental medical research to applied clinical research, in order to improve health care and the health of people.

In GlycanTrigger, LUMC leads the mapping of gut mucosa glycome in the transition from health to chronic inflammation, and the integrated data analysis.

www.universiteitleiden.nl

Sorbonne University, located in the heart of Paris, is a multidisciplinary, research-intensive, world-class university. With its 55,300 students, 6,400 academic researchers and partner researchers, and 3,600 administrative and technical staff, Sorbonne is committed to the success of its students and to meeting the scientific challenges of the 21st century, promoting diversity, creativity, innovation and openness to the world.

In GlycanTrigger, Sorbonne leads the understanding of the biologic impact of changes in gut glycome in microbial and immunological dynamics, concretely the impact of an altered host glycocalyx on the gut microbial composition and function.

www.sorbonne-universite.fr

Charité is one of the largest university hospitals in Europe, with four campuses and over 100 different Departments and Institutes. All of their clinical care, research and teaching are delivered by physicians and researchers of the highest international standard. Charité is internationally renowned for its excellence in teaching and training. Charité – Universitätsmedizin Berlin represents a single medical faculty, which serves both Humboldt Universität zu Berlin and Freie Universität Berlin.

In GlycanTrigger, Charité contributes to exploring how changes in gut mucosa glycans activate both innate and humoral immune responses.

www.charite.de

GLSMED Learning Health (GLSMED LH) is a distribution company for products, equipment, and medical devices. It is owned by the biggest private group of hospitals in Portugal, Luz Saúde, the biggest insurance company in Portugal, Fidelidade, and one of the biggest Chinese conglomerates in the world, Fosun.

In GlycanTrigger, GLSMED LH leads the evaluation of a novel  therapeutic strategy in preventing the shift from health to inflammation.

www.linkedin.com/showcase/glsmed/

The Icahn School of Medicine at Mount Sinai is an international leader in medical and scientific training, biomedical research, and patient care. It is the medical school for the Mount Sinai Health System, which includes eight hospital campuses in the New York metropolitan area, and has more than 5,000 faculty and nearly 2,000 students, residents, and fellows. They aim to pursue ideas that often challenge conventional wisdom to revolutionize the practice of medicine and produce dramatically better outcomes for patients.

In GlycanTrigger, Mount Sinai collaborates in defining the gut glycome map during the transition from health-to-chronic inflammation.

www.icahn.mssm.edu

The European Federation of Crohn’s & Ulcerative Colitis Associations (EFCCA) represents 46 national Crohn’s and Ulcerative Colitis (collectively known as Inflammatory Bowel Disease or IBD) patient associations. They are an organization of people united with the commitment to improve the life of over 10 million people living with IBD worldwide (3.4 million in Europe alone) and to give them a louder voice and more visibility. Their vision is to find a cure for IBD, identified as a recognisable chronic illness.

In GlycanTrigger, EFCCA contributes to the dissemination, exploitation and communication activities, more precisely in the stakeholder mapping, engagement and wider outreach, in the guidelines for policy engagement and health literacy improvement, and in the development of two training for change events.

www.efcca.org

Sociedade Portuguesa de Inovação (SPI) is a consulting firm established in 1996, with a deep knowledge of the private and public sectors, as well as the processes that allow its clients to foster innovation, be competitive, and generate growth. The Group includes SPI, SPI Azores, SPI China, SPI Spain, SPI USA, SPI Ventures, Turivã, Herdade da Torre Vã and an affiliate office in Brussels, through a partnership with the European Business & Innovation Network (EBN).

In GlycanTrigger, SPI leads the dissemination, exploitation and communication activities, more specifically the dissemination, exploitation and communication plan, the project marketing and communication activities, clustering and networking, and the implementation of two training for change events.

www.spi.pt

Ludger is an industry leader specialised in glycomics and glycoanalytical technology to support biopharmaceutical realisation and translational medicine. Their scientists are experts in detailed glycan analysis and characterisation, and their expertise can be applied to both biopharmaceuticals and glycoconjugates relevant to medical research.

In GlycanTrigger, Ludger collaborates in understanding how certain sugar molecules (glycans) in the gut can cause harmful reactions in the body, and how we can detect them in circulation .

www.ludger.com

Work plan

The project is composed by 6 work packages (WP) that are interconnected to allow a continuous cross-communication, in a way that each WP supports and guides the others.

WP1

In WP1 we will define the gut glycome map — the composition of sugars (glycans) at the gut mucosa surface — of the transition from health-to-chronic inflammation. In this WP we will analyse the glycans composition of the gut glycocalyx along health to intestinal inflammation transition.

WP2

GlycanTrigger’s WP2 studies how changes in the sugars on the surface of gut cells (called the glycocalyx) can affect the bacteria that live in our gut (microbiota). This WP is particularly interested in how these glycan changes might lead to microbiota alterations and to inflammation. By understanding these processes better, we hope to find ways to prevent or treat gut inflammation.

WP3

GlycanTrigger’s WP3 looks at how changes in the sugars on the surface of cells in the gut can lead to activation of inflammation. This WP also looks at how these glycan changes might lead to the production of antibodies, which can further contribute to the inflammatory process. By studying these processes, we hope to gain a better understanding of how gut inflammation starts and how we might be able to stop it.

WP4

GlycanTrigger’s WP4 intends to develop a preventive approach for counteracting changes in host mucosa glycome (glycocalyx) as a strategy to prevent perturbations in host-microbiota interactions associated with prevention of health to inflammation transition.

WP5

GlycanTrigger’s WP5 develops a communication, dissemination and exploitation strategy with a set of activities, tools and materials, that include a website, in-hand dissemination tools, press releases, social media accounts, newsletters, podcast episodes, videos, scientific publications, organisation of project events and participation in non-project events. In addition, all relevant EFCCA sister organisations will be mapped and engaged, in order to maximise their involvement in the project. This WP is also responsible for implementing a patient empowerment-centred approach for an IBD transformative change.

WP6

GlycanTrigger’s WP6 provides the consortium the leadership, management and administrative services, making sure all the other parts of the project run smoothly. This WP creates and implements a set of rules for financial and administrative management and ensures everyone follows them, complying with the rules of Horizon Europe. Moreover, a GlycanTrigger External Advisory Board is established as part of this WP to support the project’s execution and offer insight and outside consultation.

Our impact

Scientific/Technological

New research on the role of glycans in inflammation and disease prevention leads to novel treatments and therapies. This knowledge helps medical professionals understand what triggers chronic inflammation and how to advise citizens to improve their health.

  • Researchers and medical professionals understand the chronic inflammation factors triggering the health-to-disease transition and subsequently provide optimal counselling to citizens for improving their health.
  • Health care professionals have access to and employ objective health indicators of chronic inflammation for monitoring the health status, establishing personalised prevention measures and improving the health outcomes for citizens.
  • Health care professionals have the scientific evidence and understanding of health-to-disease transition to develop and use improved guidelines for personalised prevention strategies to tackle chronic diseases.

Economic

Reduced burden of chronic diseases on healthcare systems. This knowledge saves money on long-term treatments and patients can make informed decisions, resulting in healthier lives and fewer healthcare costs. This approach leads to a reduced burden of chronic inflammatory diseases worldwide, which can extend beyond CD and IBD to many other immune-related disorders.

  • Reduced disease burden, including at old ages or in other vulnerable stages of life.
  • Increased engagement in and adherence to effective strategies for health promotion, diseases prevention and treatment

Societal

With access to this knowledge, citizens can actively manage their own health, make healthier choices, and reduce their risk for developing chronic diseases. They can trust in knowledge-based health interventions and guidance from health authorities, leading to increased engagement in and adherence to effective strategies for health promotion, disease prevention, and treatment. This leads to patient empowerment and independence in health decision-making, resulting in a more informed and healthier society.

  • Citizens are better informed to actively manage their own health, have the tools to maintain their healthy status, improve their health and reduce their risk for developing chronic diseases.
  • Citizens adopt healthier lifestyles and behaviours, make healthier choices and maintain longer a healthy, independent and active life.
  • Citizens are able and empowered to better manage their own physical and mental health and well-being, monitor their health, and interact with their doctors and health care providers.
  • Citizens´ trust in knowledge-based health interventions and in guidance from health authorities is strengthened, including through improved health literacy.

Synergies

GlycanTrigger aims to collaborate with its Sister Projects – EU projects funded by the call topic “Personalised Blueprint of Chronic inflammation in health-to-disease transition” (HORIZON-HLTH-2022-STAYHLTH-02-01)

ENDOTARGET

Systemic Endotoxemia as the driver of chronic inflammation – Biomarkers and novel therapeutic targets for Arthritis

Coordinator: Helsinki University Hospital, Finland

The ENDOTARGET project aims to explore the relationship between gut microbiota, gut permeability, and systemic endotoxemia with a special focus on the three most abundant rheumatic diseases (RDs): osteoarthritis, rheumatoid arthritis and spondylarthritis.

www.endotargetproject.eu

MIGUT-HEALTH

Personalised blueprint intestinal health

Coordinator: University Hospital Schleswig Holstein, Germany

The miGut-Health consortium aims to develop a personalised blueprint of intestinal health to predict and prevent inflammatory bowel disease. The overall goal is to deliver interdisciplinary solutions (molecular, nutritional, eHealth and patient engagement/empowerment level) for health promotion and disease prevention that would enable active patient engagement in health and self-care management.

www.migut-health.eu

IMMEDIATE

Imminent Disease Prediction and Prevention at the Environment Host Interface

Coordinator: Charité – Universitätsmedizin Berlin, Germany

IMMEDIATE aims to investigate and explore the diet-microbiome-immunometabolism-axis as a sensor for health-to-disease transition and evaluate strategies to maintain an individual’s well-being. The identification of clinical and omics-derived biomarkers will – by employing AI algorithms – yield a personalised risk/resilience score of chronic inflammation and thus a better prediction of an individual’s risk of transition towards disease.

www.immediate-project.eu

PROTO

Advanced PeRsOnalized Therapies for Osteoarthritis – Tackling inflammation to improve patient outcomes

Coordinator: Charité – Universitätsmedizin Berlin, Germany

The PROTO consortium strives to implement new evidence- and patient-centred treatment strategies for early- and pre-disease stages in osteoarthritis (OA) patients. The project intends to prevent health to disease transition by restoring physiological movement and reducing joint inflammation.

www.proto-horizon.eu

IPROLEPSIS

Psoriatic arthritis inflammation explained through multi-source data analysis guiding a novel personalised digital care ecosystem

Coordinator: Aristotle University of Thessaloniki, Greece

PROLEPSIS aspires to shed light upon the health to Psoriatic Arthritis (PsA) transition with a comprehensive multiscale/multifactorial PsA model employing novel trustworthy AI-based analysis of multisource and heterogenous data. The project aims to identify key drivers of PsA onset and supports personalised models for PsA risk/progression prediction and monitoring as well as associated inflammation detection and severity assessment.

www.iprolepsis.eu

AIDA

An Artificially Intelligent Diagnostic Assistant for gastric inflammation

Coordinator: Engineering Ingegneria Informatica SpA, Italy

AIDA aims (i) to help researchers to understand the mechanisms that trigger gastric oncogenesis, (ii) to help clinicians diagnose precancerous inflammation at the earliest possible stage, (iii) to select personalised therapeutic strategies for treatment and follow-up, and (iv) to make personalised recommendations for monitoring patient health status, thus contributing to gastric cancer prevention.

www.project-aida.eu

INITIALISE

Inflammation in human early life: targeting impacts on life-course health

Coordinator: University of Turku, Finland

INITIALISE focuses on the development of the human immune system in early life, which impacts the risks of several diseases later in life, particularly immune-mediated diseases such as allergies, asthma, and autoimmunity. With the help of intersecting multiple cohorts and existing biobanks, applying state-of-the art technologies for exposure analyses and immune system investigation, the project will try to understand the environmental factors shaping human immune systems early in life, their mechanisms of action, and impact on life-course health.

www.initialise-project.eu

HALT-RONIN

Discovering chronic inflammation biomarkers that define key stages in the Healthy-to-NASH (non-alcoholic steatohepatitis) transition to inform early prevention and treatment strategies

Coordinator: Universidad Complutense de Madrid, Spain

Halt-RONIN aims to uncover the early triggers of Non-alcoholic fatty liver disease (NAFLD) initiation and complex mechanistic drivers of disease progression by implementing a systems biology approach with integrative disease modelling resulting in opportunities for the improvement of the existing detection methods, providing a blueprint to inform personalised intervention strategies and drug discovery for NAFLD.

www.halt-ronin.com

INTERCEPT-T2D

Early Interception of Inflammatory-mediated Type 2 Diabetes

Coordinator: Institut national de la santé et de la recherche médicale, France

The overall concept of INTERCEPT-T2D is to establish whether an inflammatory-mediated profile contributes to the onset of type 2 diabetes (T2D) complications, thus enabling the identification of patients most at risk of complications and the design of personalised prevention measures. The project will bring a new and clinically relevant dimension in T2D care considering diagnosis inflammatory parameters that are of importance for the transition to T2D-related complications.

CARE-IN-HEALTH

CArdiovascularREsolution of INflammation to promote HEALTH

Coordinator: Institut national de la santé et de la recherche médicale, France

Chronic inflammation is a critical residual risk for the health to cardiovascular diseases transition with limited possibilities to stop it without causing immunosuppression. To tackle this issue, CARE-IN-HEALTH proposes to identify the resolution of inflammation to develop new prevention strategies to lower inflammation with a retained immune defence against infections to sustainably stay healthy.

PREVALUNG EU

Biomarkers affecting the transition from cardiovascular disease to lung cancer – towards stratified interception

Coordinator: Institute Gustave Roussy, France

Based on multiple OMIC- approaches, PREVALUNG EU will conduct a prospective study in cardiovascular disease (CVD) tobacco consumers. This will allow to unveil four drivers of early carcinogenesis leading to actionable biomarkers that can be harnessed to pioneer personalised interceptive measures.

PRAESIIDIUM

Physics informed machine learning-based prediction and reversion of impaired fasting glucose management

Coordinator: Spindox Labs, Italy

The aim of PRAESIIDIUM is to develop a prototype tool for the real-time prediction of the prediabetic risk based on a series of patient-specific mathematical models that simulate metabolism, pancreas hormone production, microbiome metabolites, inflammatory process and immune system response. The prediction algorithm will be based on a “physics-informed machine learning” approach.