Availability of Serum Testing for LPS, Zonulin, and sCD14
Serum testing for lipopolysaccharides (LPS), zonulin, and soluble CD14 (sCD14) is available through research and specialized commercial laboratories, but these tests are not standardized for routine clinical use and lack FDA clearance for diagnostic purposes.
Current Testing Landscape
LPS Testing Availability
- LPS detection is primarily performed using the limulus amebocyte lysate (LAL) assay, which is commercially available from many manufacturers and can detect endotoxin levels as low as 0.02 ng/mL (0.1 EU/mL) 1
- Multiple assay platforms exist including chromogenic LAL assays, modified recombinant Factor C assays (Endozyme, EndoLISA), and cell-based assays such as TLR4 reporter gene assays 1
- These tests are routinely used in research settings and pharmaceutical quality control but are not standardized as clinical diagnostic tests 1
Zonulin Testing Availability
- Commercial ELISA kits for serum zonulin are available from manufacturers including CUSABIO (Wuhan, China) and Immundiagnostik AG (Bensheim, Germany) 2
- Critical caveat: Current commercial zonulin assays do not actually detect zonulin (prehaptoglobin-2) but instead detect haptoglobin and complement C3, making them unreliable markers of intestinal permeability 2
- Despite widespread use in research, these assays lack validation for clinical diagnostic purposes and show significant methodological inconsistencies 2, 3
sCD14 Testing Availability
- Soluble CD14 can be measured by ELISA in research laboratories 4, 5
- This marker is used primarily in research contexts to assess monocyte activation and endotoxin exposure 5
- No FDA-cleared diagnostic test exists for clinical use
Important Limitations and Pitfalls
Lack of Clinical Validation
- None of these biomarkers have established reference ranges, clinical decision thresholds, or validated diagnostic criteria for specific diseases 2, 3
- The tests are not included in standard clinical laboratory panels and are not reimbursed by insurance for diagnostic purposes
Methodological Issues with Zonulin Testing
- Studies demonstrate that zonulin levels measured by commercial assays do not correlate with the gold standard lactulose-rhamnose ratio for intestinal permeability (r = -0.016, P = 0.929) 3
- Mass spectrometry analysis confirms that commercial zonulin assays detect complement C3 and haptoglobin rather than actual zonulin protein 2
- Exercise extreme caution in interpreting "zonulin" results, as they may reflect systemic inflammation (via haptoglobin/C3) rather than gut permeability 2
LPS Testing Considerations
- LPS assays can be affected by low endotoxin recovery (LER), where chelating agents and surfactants mask endotoxin detection in Factor C-based assays 1
- Cell-based TLR4/CD14/MD2 assays may be more reliable for detecting monomeric LPS compared to Factor C-based methods 1
Research Context Only
- These biomarkers have been studied in research settings for conditions including type 2 diabetes 4, COVID-19 6, and metabolic disorders 5
- Studies show elevated LPS and zonulin levels correlate with inflammatory markers (TNF-α, IL-6, CRP) in disease states 4, 6, 5
- However, the clinical utility for diagnosis, treatment decisions, or monitoring remains unproven 2, 3
Practical Recommendation
If you are considering these tests for clinical decision-making, do not order them. The lack of standardization, questionable validity (especially for zonulin), and absence of established clinical thresholds make these tests inappropriate for patient care decisions. If intestinal permeability assessment is clinically necessary, the gold standard lactulose-rhamnose differential sugar absorption test should be used instead 3. For research purposes only, contact specialized research laboratories or commercial vendors directly, but recognize that results cannot guide clinical management.