Colonic paracellular permeability and circulating zonulin-related proteins

Area of Science:

• Gastroenterology
• Immunology
• Gut-Brain Axis Research

Background:

• Irritable bowel syndrome (IBS) is a gut-brain disorder linked to increased intestinal permeability.
• Zonulin is proposed to regulate gut barrier function and is often measured as a biomarker for gastrointestinal permeability.
• Pre-haptoglobin 2 (pre-HP2) has also been investigated in relation to gut health.

Purpose of the Study:

• To investigate the correlation between colonic paracellular permeability and circulating levels of zonulin and pre-HP2 in IBS patients.
• To evaluate the reliability of circulating zonulin and pre-HP2 as markers for gut permeability.
• To assess the specificity of a commonly used zonulin assay.

Main Methods:

• Colonic biopsies from IBS patients and healthy controls (HC) were analyzed for permeability using Ussing chambers.
• Zonulin levels were measured in plasma from IBS patients, HC, and celiac disease (CeD) patients using ELISA.
• Pre-HP2 levels and human haptoglobin (HP) genotype were determined, and zonulin assay specificity was verified.

Main Results:

• Increased colonic permeability in IBS biopsies positively correlated with biopsy zonulin levels but negatively with plasma zonulin.
• No agreement was found between circulating zonulin and pre-HP2 levels.
• The Cusabio zonulin kit showed non-specificity, detecting zonulin in individuals lacking pre-HP2.
• CeD patients had higher pre-HP2 and zonulin levels than HC, which decreased after a gluten-free diet.

Conclusions:

• Circulating zonulin and pre-HP2 do not accurately represent colonic permeability in IBS.
• The Cusabio zonulin assay is not specific for zonulin, necessitating cautious interpretation of previous studies using this kit.
• Further research is needed to identify reliable biomarkers for gastrointestinal permeability.