Zonulin / leaky gut

Zonulin regulates the permeability of the tight junctions in the intestinal epithelium. Raised zonulin levels are looked at as an indication of increased intestinal permeability (leaky gut). Increased permeability is investigated in connection with systemic inflammation, food intolerances and histamine problems. In studies, gliadin from gluten and certain gut bacteria stimulate zonulin release.

What zonulin does in the body

The cells of the gut lining are sealed to one another by protein connections called tight junctions. They determine what passes between the cells into the gut wall – water and small particles yes, larger molecules, food components and bacteria no. Zonulin is a signalling protein released by the gut cells themselves; the precursor of haptoglobin-2 has been identified as zonulin. It binds to receptors on the cell surface and triggers a rearrangement of the cell scaffold that opens the tight junctions temporarily. In studies, the main triggers are bacteria in the small intestine and gliadin, a component of gluten. The brief opening flushes water into the gut and so helps to wash out pathogens. Common test methods detect structurally related proteins as well as zonulin; the value is therefore read together with other barrier and inflammation markers.

Low zonulin – what does it mean?

A low value is the normal case: the gut cells release little zonulin, and the tight junctions remain largely closed. People who carry only the haptoglobin-1 variant from birth do not make the zonulin precursor at all – in them low values are genetically determined and say nothing about the permeability of the gut wall.

Raised zonulin – what happens in the body?

If a lot of zonulin is released persistently, the tight junctions stay open for longer. More substances from the gut contents then pass between the cells into the gut wall: incompletely digested food proteins, bacterial components such as lipopolysaccharides and metabolic products of the gut flora. The immune cells in the gut wall react to this and release inflammatory messengers that loosen the tight junctions further – so the increased permeability can reinforce itself. Some of the messengers and bacterial components also reach other organs via the blood. Raised values have been observed in studies in coeliac disease, type 1 diabetes, chronic inflammatory bowel diseases and with an altered gut flora.

The interpretation is given in your report.