The TRUTH About Zonulin
In recent years, “leaky gut” (aka enhanced/increased intestinal permeability, or as I call it, “pasta strainer gut”) has been clinically linked to so many chronic diseases. IBD, IBS, autoimmunity, liver disease, autism, eczema, and the list goes on. A sealed gut has become one of the cornerstone determinants of overall health. But how do you know your own personal pasta strainer status and if your gut is negatively impacting your health?
The most popular leaky gut marker being used in the functional space is fecal zonulin (though zonulin can also be measured in serum). Zonulin is a small protein in the gut that regulates cellular tight junctions, or spaces between the cells that form a single layer barrier throughout the small intestines. Higher zonulin = increased space between the cells, and increased leaky gut. Lower zonulin = more tightly packed cells, and appropriate intestinal permeability.
On one side of the cellular intestinal barrier is the innards of the digestive tract, where we have food, microbes, stool, toxins, and a variety of other molecules. On the other side is access to the rest of the body: blood, immune system, lymphatic system, joints, and anywhere else the gut’s contents may venture off to.
We don’t want the contents of the gut to escape via higher zonulin and spill out into systemic circulation. That’s bad. Very bad. Because as I mentioned above, higher zonulin = increased leaky gut = risk of many chronic diseases.
So, you see, zonulin is a very important protein to keep the gut’s contents inside the gut. And zonulin itself is a fairly large protein that’s produced in the gut that should not be leaking into the bloodstream, so its presence is considered troublesome.
The problems unfold…
However, zonulin is not as reliable of a test marker for leaky gut as was once thought, for several reasons.
- Clinical research shows that elevated levels of zonulin don’t always exist in those with specific diagnoses that would definitively raise zonulin (e.g. active celiac disease) or in those whose damaged gut bacteria contributing to their diagnoses would contribute to leaky gut (e.g. depression, autism, diabetes, metabolic syndrome).
- Since zonulin is very short-acting, levels of zonulin fluctuate throughout the day and throughout the week, including from exposure to certain foods (particularly gluten), making this marker less useful.
- For some people whose health dramatically improved after gut healing (suggesting resolution of leaky gut), repeated zonulin testing continued to show elevated zonulin levels, suggesting the opposite of their experiences.
- Due to the lab techniques being used to check for zonulin, scientists found that the zonulin lab test wasn’t actually measuring and reporting zonulin, but instead some other mystery protein(s). To me, this is the most concerning.
So what’s a girl to do to see if there’s pasta sieve activity going on in her gut?
Perhaps try a different test. Or not test at all.
But some people are data-driven, and I respect that! In this case, there are 2 options:
- Anti-zonulin test. Ongoing actual high zonulin release into the bloodstream will eventually attract attention from the immune system. And not the good kind. The immune system will start to produce specific antibodies against zonulin, and these CAN be accurately measured by the lab. Researchers had better luck at more consistently detecting higher levels of anti-zonulin than zonulin in celiac patients, capturing more cases of expected leaky gut. Anti-zonulin is a blood test.
- Lactulose-mannitol test. This test is considered the gold standard of intestinal permeability detection. The idea is that because lactulose molecules are large, with appropriately releasing zonulin keeping the cells relatively tightly close together, the lactulose molecules will be forced to continue down through the GI tract and get excreted. If lactulose is found, it’s because the small intestines are indeed leaky. This test is a urine test, after drinking a special lactulose-mannitol drink, and this test can be a hassle to do.
I’ve stopped relying so much on testing.
Instead, I focus on indicators like nutrient malabsorption on a healthy diet, poor growth in children, food reactivity, allergy symptoms, autoimmunity (including Celiac, IBD, but also outside the gut as well), and the presence of lipopolysaccharide-producing bacteria (the ones that contribute to leaky gut!), parasites, and Candida from stool tests. Because immune system dysfunction can often be associated with leaky gut, we see them together often. And if a client really wants data to validate the state of their gut or if results on paper boosts their motivation, I’m happy to help with making this happen.