WP4. Biomarkers related to gut barrier functions (P1,P2,P3,P4 leader; M1-M36)

Gut permeability can be assessed in vivo by the ingestion of inert marker molecules (53Cr-EDTA, different sugars). However these tests are relatively complex and not always well accepted by the patients. Moreover, they can be performed only in prospective trials. Therefore other markers are required, which can be measured in blood, urine or stool. The measurement of bacterial elements in serum indicates a translocation from the gut lumen into the blood. Another way to measure gut permeability is to examine the inverse flux from the blood to the lumen. Albumin is the most abundant protein in blood and an increase of this protein in stool indicates a disturbed gut barrier. As albumin is sensitive to proteases, it is particularly adapted to assess the colon barrier function, where the gut microbiota is most abundant. Enterocytes of the intestinal mucosal layer, involved in the uptake of fatty acids, produce the intestinal fatty acid binding protein (i-FABP). This protein is specific for intestinal cells and its measurement in the blood was shown to be a marker of intestinal tissue injury. Calprotectin is a protein released by neutrophils and was shown to be a marker for gut inflammation when measured in feces. Beside immune cells and enterocytes, the gut barrier involves tight-junction proteins controlling the paracellular flux between blood and lumen. Zonulin is expressed in both liver and intestinal cells and was shown to regulate the tight junctions. In the gut it can be modulated by the microbiota. It can be measured in feces, where a high concentration correlates with increased permeability.

Task 4.1 Selection of key biomarkers for evaluation of the gut barrier function.

Task 4.2. Measure of biomarkers related to gut barrier in existing cohorts

Task 4.3. Measure of biomarkers related to gut barrier in the FiberTAG intervention study

Deliverables (D) and Milestones (M) of WP4 with delivery date

D4.1 report on the selected relevant biomarkers (M8)
D4.2 SOPs for biological sample processing for selected biomarkers (M9)
D4.3 report on biomarkers related to gut barrier functions for existing cohorts (M24)
D4.4 report on biomarkers related to gut barrier functions for intervention study (M33)
D4.5 report on correlative analyses (M27,M36)
M4.1 selection of non-invasive biomarkers of gut barriers functions (M7)

Risk: It might be that the gut permeability is only slightly impacted by the different DF consumptions.

Mitigation measure: We selected different types of markers and will analyze different cohorts with or without disease to maximize the chances of detecting DF impact on gut barrier functions