Laboratory Testing for Intestinal Permeability

Laboratory testing is designed to validate a clinical hypothesis and confirm a diagnosis. Tests can also serve as status checks, measured over time to monitor treatment progress. To be truly useful, a test must answer the critical question: "What actionable information does this provide?"

For example, a reliable test for intestinal permeability (commonly known as "leaky gut") should clearly indicate the presence or absence of the condition. Tests that yield ambiguous results provide guidance but may lack the confidence needed for definitive clinical decisions.

Available Tests

1. Lactulose/Mannitol Test
   This test involves ingesting two types of sugars: lactulose, which should not normally be absorbed, and mannitol, which is fully absorbed. If lactulose appears in the urine, it suggests intestinal permeability. However, this test evaluates only the "leak pathway" (larger pores) and does not assess the smaller-pore pathway of paracellular intestinal permeability.

2. Serum IgM/IgG Antibodies
   Antibodies targeting intestinal barrier proteins (e.g., zonulin, occludin) or lipopolysaccharides (LPS) can indicate chronic or current paracellular intestinal permeability. These markers are predictive and supported by research.

3. Fecal Zonulin Levels
   While fecal zonulin levels are often promoted as predictive, research shows that serum or tissue zonulin is more reliable.

Limitations of Current Testing
None of the commercially available tests can pinpoint the exact location of permeability (e.g., small intestine vs. large intestine). This distinction is critical, as the healing strategies differ for these areas. Despite their limitations, these tests can be valuable, especially in conditions like IBS-D or IBD, where intestinal permeability is often assumed.