Serum zonulin (commercial assay): what it measures, and what it does not

• Whatever protein the specific commercial kit binds. Published validation work reports that widely used kits do not specifically detect pre-haptoglobin-2.

  Population / model: Serum or plasma.. Sources: BL-REF-0004 (verification pending), BL-REF-0015 (verification pending).

No direct human evidence is claimed for this question.

No animal or in-vitro evidence is claimed for this question.

• The measurement is read as a proxy for the biology of interest

  Reading a numeric zonulin value as a quantified 'leaky gut' score, then tracking it as a treatment response marker.

• The measurement is read as a description of the sample assayed

  This reading stays inside what the assay detects. It does not provide a validated measure of intestinal permeability, and it does not indicate barrier repair or barrier damage over time.

• That intestinal permeability is increased, decreased, or normal.
• Which protein the reported concentration corresponds to, given published antibody-specificity findings.
• Any comparison against a result from a different kit or platform.

• Repeated values from the same kit describe the reproducibility of that kit, not a trajectory of barrier function.
• A falling or rising series cannot be read as barrier repair or barrier damage while the analyte identity is unresolved.

0 of 2 reference(s) have completed owner verification. Records awaiting verification are listed for transparency and are not presented as confirmed evidence.

1. BL-REF-0004verification pending

   Scheffler L, Crane A, Heyne H, et al. (2018). Widely Used Commercial ELISA Does Not Detect Precursor of Haptoglobin2, but Recognizes Properdin as a Potential Second Member of the Zonulin Family. Frontiers in Endocrinology. doi:10.3389/fendo.2018.00022

   https://pubmed.ncbi.nlm.nih.gov/29459849/

   Scope: Assay-specificity study. Reports that a widely used commercial 'zonulin' ELISA does not detect pre-haptoglobin-2 and instead recognises properdin, i.e. the kit does not measure the analyte its name implies.

   Does not support: Does not establish that intestinal permeability is unimportant, and does not establish that any alternative permeability measure is validated. It is a finding about what the commercial kit binds.

   Status: reference verification pending

2. BL-REF-0015verification pending

   Ajamian M, Steer D, Rosella G, Gibson PR (2019). Serum zonulin as a marker of intestinal mucosal barrier function: May not be what it seems. PLoS ONE. doi:10.1371/journal.pone.0210728

   Scope: Analytical evaluation of commercial serum 'zonulin' assays. Reports that the antibodies used do not identify pre-haptoglobin-2 and that different kits do not agree, i.e. an assay-identity problem.

   Does not support: Does not establish that barrier function is irrelevant, and does not adjudicate any mechanistic model of permeability. It constrains what a serum zonulin number can be read as.

   Status: reference verification pending

• Any interpretation of an individual reader's result.
• A reference range, cut-off, or decision threshold.
• That this test should or should not be performed.

Educational systems-biology material. Not medical advice, not a diagnosis, and not a treatment recommendation. No dosing, protocol, or personal lab interpretation is given here.