Zonulin Family Protein- Serum Test


Elevated serum levels of a zonulin family protein (ZFP) are correlated with abnormal results of the Lactulose Mannitol test; the long-accepted standard for intestinal permeability (“leaky gut”). The test may be used as a clinically equivalent alternative for those who don’t want to use the “sugar” load test.

NOTE: additional laboratory fee applies for drawing and preparing the sample. Price includes postage.


Zonulin family protein (ZFP) is a protein that has been correlated with abnormal Lactulose Mannitol test; the long-accepted standard for intestinal permeability. Elevated levels of ZFP have been associated with metabolic syndrome, obesity, and several autoimmune, inflammatory and neoplastic diseases. Such diseases include Celiac disease, type I diabetes, juvenile nonalcoholic fatty liver disease, and evidence is accumulating for multiple sclerosis, rheumatoid arthritis, asthma, and inflammatory bowel disease.

Zonulin may open the tight junctions between the cells in the wall of the intestine. Elevated levels of zonulin have been identified as the potential doorway to intestinal hyperpermeability (commonly called “leaky gut syndrome”). Increased intestinal permeability may be a contributory factor in Crohn’s Disease and other inflammatory, autoimmune and gastro-intestinal diseases as well as on symptoms or even diseases occuring outside the digestive system.

The pathway from the intestinal lumen and the circulatory system is normally tightly regulated. If zonulin is up-regulated for excessive periods of time an increase in antigens can cause both intestinal and extra-intestinal autoimmune disorders in genetically susceptible individuals.  Serum zonulin levels may be higher in obese adults, and in those with impaired glucose tolerance. Elevated serum levels of zonulin and increased permeability are commonly observed in patients at risk of developing Crohn’s disease and type 1 diabetes – even before symptom begin!  High serum ZFP levels may also be seen with the use of corticosteroids and non-steroidal anti-inflammatory drugs.

A limitation of zonulin in the blood stream is that it is also released from fat tissue so if you have high BMI or a metabolic condition (such as PCOS) you might have high levels of zonulin that are not coming from the gut tight junctions disassembling.

You can read more about intestinal permeability here.

zonulin test

Sample report of a zonulin serum test

Who Should Test Serum Zonulin Family Protein?

If you have, or have recently had, any of the following common conditions you should consider a serum zonulin test.

Note that there is lack of clarity amongst researchers as to whether this means that serum ZFP is a useful marker of intestinal permeability compared to faecal zonulin. At least one study found no correlation between serum and stool zonulin levels, but another found serum levels correlated with abnormal results of the Lactulose Mannitol test, which is the long-accepted standard for intestinal permeability testing.

leaky gut, zonulin

A gut that leaks allows more through the intestinal wall than is desirable.

Test method: ELISA


  • https://pubmed.ncbi.nlm.nih.gov/28537581/
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372598/
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053220/
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372911/
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207627/
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163724/
  • https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210728

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