GlycanTrigger's 6-year project

[asadmom]

GlycanTigger is an international collaboration targeting in IBD detection and prevention. They launched their 6-year research earlier this year.

What are your thoughts on their hypothesis?
@kiny

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. 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.

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.

Work Plan 1
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.

WP 2
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.

WP 3
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.

See more here: https://glycantrigger.eu/

 

[kiny]

The term IBD doesn't tell you which disease they are looking at.

The glycocalyx is barely present on ileal M cells, where the interaction takes place between peyer's patches and microbes. Glycocalyx develops at infantile age, not at puberty when crohn's disease and peyer's patches develop. I don't believe there is a drawn out "preclinical" phase in crohn's disease, crohn' disease is acute. I'm not sure this research is very relevant to crohn's disease, maybe more to UC, idk.

 

[kiny]

The glycocalyx is barely present on ileal M cells, where the interaction takes place between peyer's patches and microbes.

Here you go, my fancy phone drawing of the ileum. Glycocalyx is rarely shown in images or drawings, you need a strong electron microscope to see it, it's in between the mucus layer and the epithelial barrier.

But because it's not present on M cells, and because I strongly believe in the involvement of M cells as a point of bacterial entry that set off the deep tranmural inflammation in crohn's disease, I have never really considered it that relevant. Disfunction would cause mucosal inflammation, not the transmural patchy inflammation seen in crohn's disease.

 

[asadmom]

Here you go, my fancy phone drawing of the ileum. Glycocalyx is rarely shown in images or drawings, you need a strong electron microscope to see it, it's in between the mucus layer and the epithelial barrier.

But because it's not present on M cells, and because I strongly believe in the involvement of M cells as a point of bacterial entry that set off the deep tranmural inflammation in crohn's disease, I have never really considered it that relevant. Disfunction would cause mucosal inflammation, not the transmural patchy inflammation seen in crohn's disease.

View attachment 4619

This is quite good.

Let me ask it way then.. why is it that these prominent researchers and the EU would invest the money/effort without seeing some evidence indicating that this pursue would be worth the next 6-years of their lives?

 

[Andersen007]

I do believe there is some sort of pre-clinical phase, at least in some Crohn's subtypes. I had IBS-D symptoms for 10+ years before obvious Crohn's symptoms started, been to GI-s a few times, no significant signs where found, but there was an increasing amount of sensitivities such as sorbitol intolerance that I didn't have until that point, and I found myself reacting more to certain foods. Then 1.5 years before my more obvious Crohn's symptoms started (all my stools being liquid), on the ileocolonoscopy they already found some mild non-specific changes in the ileum macroscopically. But they deemed it not clinically significant, as they see it with some frequency in young adults' terminal ileum so didn't even make a biopsy. Then later, my Crohn's diagnosis ileocolonoscopy showed 2 fairly small apthous ulcers, so they had to put MRE and calprotectin next to it to make a diagnosis. So in my case I believe it was fairly gradual.