Zonulin: The Gut Marker Linking Inflammation and Autism Symptoms

In 2019, I heard Dr Federico Balzola speak at a medical conference. I had been testing zonulin for years, convinced it held clinical value, but it wasn’t until that talk that I saw just how central it is to understanding gut barrier function. Dr Balzola described zonulin as the key to uncovering hidden gut inflammation – the quiet kind that can drive food sensitivities, frequent infections, eczema, anxiety, irritability, poor sleep, and changes in focus or behaviour.

At the time, this link between gut and brain was still debated. Today, the evidence has arrived. A 2025 study from Mansoura University Hospital in Egypt confirmed what Dr Balzola recognised years ago: children with autism have significantly higher zonulin levels, and the higher the zonulin, the more severe the symptoms.

What Zonulin Tells Us

Zonulin works like the gatekeeper of the gut. The gut lining is made of tiny cells that fit closely together, forming a wall that decides what can pass through to the bloodstream and what should stay inside the gut.

When zonulin levels go up, those joins loosen and the wall starts to leak — what many people call a “leaky gut.” This means bits of food, bacteria, and toxins can slip through where they shouldn’t. Once in the bloodstream, they can set off the immune system and cause inflammation that spreads through the body. Over time, this can affect mood, sleep, focus, and behaviour.

Certain things make zonulin rise and keep it high – gluten, gut bacteria imbalances, and stress are the main ones. Gluten is especially strong: research shows it can raise zonulin in everyone, not just people with coeliac disease. In some children, this “open signal” lasts too long, leaving the gut wall open and inflamed.

How This Looks in Children

When the gut barrier is compromised, the effects can be wide-ranging. Parents often notice mood swings, irritability, hyperactivity, poor sleep, sensory overload, or regression after illness or dietary exposure.

The Evidence

In a 2025 Egyptian study, zonulin was measured in serum in 53 autistic children and 53 controls. The difference was striking:
– Autistic children averaged 73 ng/ml
– Neurotypical children averaged 22 ng/ml
– Above 47 ng/ml the test identified autism with 100 percent sensitivity and specificity
The higher the zonulin, the more severe the gut and behavioural symptoms, with a near-perfect correlation (r = 0.9).

A Simple Stool Test with Real Insight

Although this study used blood samples, multiple peer-reviewed papers show that stool zonulin is an equally valid and practical way to assess intestinal permeability because it reflects local gut activity directly and avoids the fluctuations seen in serum due to transient immune activation.

The stool test is simple – no needles, no hospital visits. Just a small sample that provides a clear picture of gut barrier integrity.

We now include stool zonulin in all gut-brain assessments. For many families, the results explain years of confusion. Many behaviours once attributed purely to autism often have an inflammatory component that can now be identified and addressed biologically.

When zonulin is high, it tells us the gut barrier is open, and inflammatory molecules are likely crossing into circulation. It gives us something real to act on.

Why It Matters

This isn’t abstract science. It explains why some children react to foods, why infections can cause setbacks, and why calming gut inflammation can improve sleep, focus, and mood. When the barrier heals, inflammation settles, and children regain balance.

What We Do When Zonulin Is High

When stool zonulin levels are elevated, we combine symptom management with root-cause work to rebuild the gut barrier and calm inflammation.

Remove Gut Triggers
Gluten, casein, and processed foods are the most common drivers of high zonulin. Even small or hidden exposures can keep the gut open and inflamed. Strict removal is essential for recovery.

Rebuild the Microbiome
Dysbiosis – particularly overgrowth of Proteobacteria or Clostridia – sustains inflammation. Rather than adding high-fibre or raw foods that can irritate a damaged gut, we use gentle, natural foods that support microbial balance: slow-cooked meats, well-cooked vegetables, bone broths, and clean fats. These feed the child without feeding the wrong bacteria.

Repair the Barrier
Once triggers are removed, the lining can heal. Butyrate, zinc carnosine, vitamin D, glutamine, and omega-3s are core supports. Colostrum can be effective, but it is not suitable for children with dairy or casein sensitivity. In those cases, serum-derived immunoglobulins or plant-based mucosal supports are better options.

Track the Change
Because zonulin is measurable, we can confirm improvement rather than guess. Falling levels show that the gut wall is sealing and that inflammation is resolving.

Bringing It All Together

Dr Balzola’s core message remains the same: hidden gut inflammation can drive neurological and behavioural symptoms. The new data confirm it. Zonulin is not just another lab result. It is a real-time marker of how the gut is talking to the brain.

For parents, this means we do not have to guess whether the gut is involved. A single stool test can tell us. And when the number is high, the message is clear – the gut barrier needs attention before the brain can fully heal.

IMPORTANT

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always consult with medical doctors or qualified functional medicine practitioners before introducing any new supplement or intervention.

Concerned about your child’s health? We’d love to have a chat with you.

 

References

Sonbol, H.M., Abdelmawgoud, A.S., El-Kady, N.M., Abdelhay, E.S., & Abdel Tawab, H.E., 2025. Serum zonulin level in autistic children and its relation to severity of symptoms: a case-control study. Scientific Reports, 15, 27802. Nature

Balzola, F., Miceli, E., Barbon, V., Mengozzi, G., Varese, P., Bellomo, A., & Sapone, A., 2005. Autistic enterocolitis: confirmation of a new inflammatory bowel disease in an Italian cohort of patients. World Journal of Gastroenterology, 11(34), 5358–5363. https://doi.org/10.3748/wjg.v11.i34.5358

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