Zonulin
The gatekeeper protein. Zonulin modulates the tight junctions between intestinal cells, controlling what passes from the gut into the bloodstream. When zonulin is elevated, these junctions open too wide— creating intestinal permeability or "leaky gut." Gluten and certain bacteria are the primary triggers.
Understanding Zonulin
Discovery
Discovered by Dr. Alessio Fasano. First identified pathway regulating intestinal permeability.
Tight Junction Function
Tight junctions seal gaps between intestinal cells. Zonulin loosens these seals.
Temporary Opening
Normal: junctions open briefly. Problem: chronic elevation keeps them open.
What Leaks Through
Bacteria, toxins, undigested food particles. Trigger immune response. Systemic inflammation.
Testing
Blood or stool zonulin testing. Elevated levels indicate increased permeability.
Other Markers
LPS antibodies, occludin, actomyosin also indicate permeability issues.
Zonulin Triggers
Gluten (Gliadin)
Primary trigger in everyone, not just celiacs. Gliadin fraction specifically.
Bacterial Overgrowth
SIBO releases zonulin. Pathogenic bacteria in small intestine.
Gut Infections
Various pathogens can trigger release. Part of immune response.
Dysbiosis
Imbalanced microbiome. Less protective bacteria. More inflammatory species.
Conditions Linked to Elevated Zonulin
Celiac Disease
Gluten-triggered autoimmunity. Highest zonulin levels. Intestinal damage.
Type 1 Diabetes
Elevated zonulin precedes onset. Leaky gut may allow triggers through.
Other Autoimmune
Rheumatoid arthritis, MS, Hashimoto's. Permeability a common factor.
IBS
Barrier dysfunction component. Especially diarrhea-predominant.
Brain Conditions
Zonulin also affects blood-brain barrier. Depression, anxiety links.
Reducing Zonulin Levels
Remove Gluten
Primary intervention. Eliminate gluten containing grains. Allow healing.
Address SIBO
Treat bacterial overgrowth if present. Reduces bacterial zonulin trigger.
L-Glutamine
Gut lining fuel. Helps repair tight junctions. 5-10g daily.
Zinc Carnosine
Supports gut barrier. Anti-inflammatory. Protects tight junctions.
Probiotics
Restore healthy microbiome. Specific strains strengthen barrier.
Larazotide
Zonulin antagonist in development. Blocks zonulin receptor. For celiac.