What functional medicine laboratory tests can I use to diagnose leaky gut (intestinal permeability)?

Laboratory Tests for Assessing Intestinal Permeability ("Leaky Gut")

There are no validated clinical tests specifically designed to diagnose "leaky gut syndrome" as it is not currently recognized as a formal medical diagnosis by major gastroenterological societies. 1

Understanding Intestinal Permeability Testing

While "leaky gut" is a popular term in functional medicine, conventional gastroenterology guidelines do not recognize it as a distinct clinical entity. Instead, they focus on diagnosing specific conditions that may involve altered intestinal permeability:

Research-Based Permeability Tests

• Lactulose/Mannitol Test: Measures the urinary excretion ratio of these two sugars after oral administration
• 51Cr-EDTA Test: Uses a radiolabeled chelate to assess intestinal barrier function
• Intestinal Permeability Assays: Using multiple ethylene glycol polymers of different molecular weights 2

These tests are primarily used in research settings and are not routinely recommended in clinical practice by major gastroenterological societies.

Recommended Diagnostic Approach for Gastrointestinal Symptoms

Instead of focusing on "leaky gut," guidelines recommend investigating for established conditions:

First-Line Testing

• Celiac Disease Screening: IgA tissue transglutaminase (tTG) with a second test to detect celiac disease in IgA-deficient patients (IgG tTG or IgG/IgA deaminated gliadin peptides) 2
• Inflammatory Markers:
  • Fecal calprotectin or fecal lactoferrin to screen for inflammatory bowel disease 2
  • Not recommended: ESR or CRP for IBD screening 2
• Infection Screening:
  • Test for Giardia (strongly recommended) 2
  • Avoid routine testing for other ova and parasites unless there's travel history to high-risk areas 2

Second-Line Testing

• Bile Acid Diarrhea Testing: Consider tests for bile acid malabsorption if available 2
  • SeHCAT nuclear medicine test (not available in US)
  • Serum 7α-hydroxy-4-cholesten-3-one (C4)
  • Serum fibroblast growth factor 19 (FGF19)
  • 48-hour stool collection for total bile acids
  • If tests unavailable, consider empiric trial of bile acid binders 2

Common Pitfalls in Assessing Intestinal Symptoms

• Failing to identify alarm features (nocturnal diarrhea, unintentional weight loss, blood in stool) 3
• Not considering medication-induced diarrhea 3
• Missing bile acid diarrhea or microscopic colitis 3
• Relying on unvalidated "leaky gut" tests marketed by some laboratories 1

Evidence Gaps and Emerging Research

Research on intestinal permeability is ongoing, with studies exploring connections between barrier dysfunction and various conditions including IBS, IBD, autoimmune disorders, and metabolic diseases 4, 5, 6. However, these connections remain largely investigational, and standardized clinical tests with established diagnostic criteria are lacking.

Some researchers have proposed using combinations of tests to assess intestinal barrier function, including:

• Serum IgG/IgA/IgM responses to tight junction proteins (occludin, zonulin)
• Markers of bacterial translocation
• Stool markers of inflammation (calprotectin, lactoferrin) 7

However, these approaches have not been incorporated into mainstream clinical guidelines.

Key Takeaway

When investigating symptoms attributed to "leaky gut," follow established diagnostic pathways for recognized gastrointestinal disorders rather than pursuing specialized "leaky gut" testing that lacks validation in clinical practice.