Zonulin is a protein secreted by intestinal cells that regulates intercellular tight junctions (1,2). Tight junctions are the connections between epithelial cells that make up the gastrointestinal lining. Zonulin increases intestinal permeability in the jejunum and ileum (3) and is considered a biomarker for barrier permeability (1,2). Tight junctions can be opened or closed, depending on the physiological need. Zonulin’s role is to open tight junctions in the gut. In the case of enteric infections, high zonulin can “open the floodgates” and flush out bacteria and toxins (1). Certain gut bacteria and gliadin (the main staple protein from wheat) can activate the zonulin system (2,4).
The intestinal barrier is a critical interface between the lumen of the gut and the internal milieu. Dysfunction of this barrier is believed to initiate immune dysfunction because it allows macromolecules from the gut lumen to pass into the bloodstream (5). Intestinal permeability, also known as “leaky gut,” has been associated with inflammatory bowel disease, celiac disease, food allergy, irritable bowel syndrome, critical illness, autoimmune diseases (6) and obesity and metabolic disease (7). In many cases, permeability precedes disease (1).
Zonulin regulates barrier permeability. Serum zonulin correlates with intestinal permeability and lactulose/mannitol tests for intestinal permeability (3,8). High serum zonulin has been associated with celiac disease, type 1 diabetes (8) insulin resistance and type I diabetes (3), cancers, neurological conditions, and autoimmune diseases (see Table 1) (1).
I love using the GI-MAP, the turn around time is efficient, it’s patient friendly and the extensive range of markers make ascertaining the imbalance in gut health easy and practical. It is also the most accurate H. pylori test out there. I recommend this to everyone as a yearly M.O.T for their health.
– Hannah Richards
Faecal Vs Serum: What’s The Difference?
Faecal zonulin is available for investigational use but has not yet been correlated with circulating (serum) levels, as of this writing. Faecal zonulin measurement may be advantageous, compared to serum zonulin when assessing intestinal permeability, as serum zonulin may constitute secretion not only from intestinal cells, but also from extraintestinal tissues such as the liver, heart and brain (9). Stool may therefore present a more appropriate specimen for analysing only intestinal production of zonulin.
As mentioned, faecal zonulin has been used for investigational use. For instance, in a human study of athletes, faecal zonulin was used as a marker of intestinal permeability. The subject’s faecal zonulin levels improved (decreased into a normal physiologic range) after 14 weeks of probiotic supplementation (2). Treatment with zeolite lowered stool levels of zonulin in athletes and presumably improved intestinal barrier function (10).
Serum zonulin is high in a number of immune-mediated conditions (1):
Inflammatory bowel disease
Type 1 diabetes
Systemic lupus erythematous
Chronic inflammatory demyelinating polyneuropathy