Measurement of serum zonulin is a very important indicator for the assessment of leaky gut. Elevated serum zonulin levels, or rather Zonulin Family Protein (ZFP), are in concordance with abnormal results of the Lactulose/Mannitol test, the best known and well-documented method to measure intestinal permeability. Elevated zonulin levels have been linked to metabolic syndrome, obesity, and certain autoimmune and inflammatory conditions as well as certain tumors. Such pathological conditions include celiac disease, type I diabetes mellitus, juvenile non-alcoholic fatty liver disease and there is significant evidence of high serum zonulin concentrations found in pathological conditions such as multiple sclerosis, rheumatoid arthritis, asthma, and inflammatory bowel diseases.
Serum zonulin measurement can be used as a clinically equivalent test to the Lactulose/Mannitol test to check for leaky gut.
What is Zonulin?
Zonulin is a protein synthesized by intestinal and liver cells and reversibly regulates intestinal permeability by forming the permeability of tight junctions between intestinal epithelial cells. Zonulin was discovered in 2000 by Alessio Fasano and his team at the University of Maryland. The team of Dr. Fasano found that cells in the human gut produced a protein that is almost identical to the cholera toxin zonula occludens, and named it zonulin. The classic symptom of cholera is profuse, watery, and debilitating diarrhea, and one of the bacterial toxins of the cholera vibrio, called zonula occludens toxin, has been found to open very quickly and reversibly tight junctions between intestinal cells in the intestinal tract. As the junctions loosen, water can flow rapidly into the intestinal lumen causing diarrhea and putting patients at serious risk of dehydration. Zonulin isolated from human intestinal cells has been shown to increase intestinal permeability in exactly the same way. Zonulin is released by intestinal cells to regulate the structure and function of tight junctions. Zonulin is, so far, the only known modulator of intercellular tight junctions that can affect the intestinal function and therefore the related immune responses and overall body health.
Zonulin and Leaky Gut
Intestinal permeability or leaky gut is a condition in which the epithelium of the small intestine is damaged, allowing indigestible food debris, toxic waste, and bacteria to "leak" through the intestine and into the bloodstream. Foreign substances entering the bloodstream can cause immune system reactions, including inflammatory and allergic reactions as well as migraines, irritable bowel syndrome, eczema, chronic fatigue, food allergies and intolerances, rheumatoid arthritis, and many others.
Normally, only the smallest molecules are allowed to pass through the well-functioning intestine. The action of zonulin allows larger molecules or even large aggregates to pass into the bloodstream and this very increased intestinal permeability is called a leaky gut. Increased intestinal permeability is believed to contribute to the development of chronic inflammation and the development of autoimmune diseases. Elevated zonulin levels are detected in various autoimmune conditions as well as during celiac disease crises. Whether a person has autoimmunity or not, the two most important factors that activate the release of zonulin are bacteria and gluten. Even in people who do not suffer from celiac disease, the proteins gluten and gliadin found in cereals, can trigger the release of zonulin and increase intestinal permeability.
Elevated serum zonulin levels and increased intestinal permeability are commonly seen in patients at risk for Crohn's disease and type 1 diabetes before the onset of symptoms. Zonulin levels may be increased with the use of corticosteroids, but in one study the use of prednisone reduced intestinal permeability in patients with Crohn's disease. The trigger associated with increased zonulin levels and the breakdown of protein complexes in tight junctions is gliadin (gluten) and the attachment of bacteria to epithelial cells. Simple sugars, sodium, and food additives such as emulsifiers, microbial transglutaminase, and nano-particles also appear to disrupt the function of the epithelial barrier.
To whom is the serum zonulin addressed
Serum zonulin measurement is useful in the examination, diagnosis, and monitoring of patients with:
- Celiac disease
- Non-celiac gluten sensitivity (seronegative celiac disease)
- Type I diabetes (insulin-dependent)
- Juvenile non-alcoholic fatty liver disease
- Multiple sclerosis
- Rheumatoid arthritis
- Inflammatory bowel diseases
- Prediabetes (abnormal glucose tolerance)
Therapeutic interventions to normalize intestinal permeability should first include the elimination of the triggers. The use of certain probiotics and prebiotics such as inulin and fructooligosaccharides has been shown to restore intestinal permeability. Other clinical interventions to repair the epithelial barrier may include dietary changes (increase in soluble fiber intake), treatment of microbial dysbiosis, support of digestive function, and possibly anti-inflammatory therapies. Anti-inflammatory therapies include supplements such as quercetin, vitamin C, curcumin, gamma-linolenic acid, omega-3 fatty acids (EPA, DHA), and aloe vera. Other nutrients such as zinc, β-carotene, pantothenic acid, and L-glutamine provide additional support to improve the function of tight junctions. The use of certain probiotics has been shown to reduce serum and fecal zonulin levels and taking inulin (approximately 10 grams per day) reduces serum zonulin levels within just five days of treatment.