SIBO and Leaky Gut: Zonulin, Endotoxemia & Intestinal Permeability

In short: “leaky gut” means increased intestinal permeability: the lining of the gut lets through more than it should. Some studies show that SIBO can increase small-intestinal permeability, and in one case it returned to normal after treatment²³. However, leaky gut is not an established diagnosis, there are no validated clinical tests for it, and it is unproven that repairing the barrier improves any disease¹. The best-established way to address leaky gut linked to SIBO is to treat the SIBO and its cause.

This guide explains what intestinal permeability is, what the research on SIBO and permeability shows, why zonulinZonulin A protein that loosens the tight junctions between intestinal cells. High levels are associated with increased intestinal permeability. and other leaky gut tests are unreliable, and what to make of leaky gut claims online.

What is intestinal permeability?

The gut lining is a barrier made of a mucus layer, a single layer of cells joined by protein seals called tight junctionsTight junctions Protein seals between neighboring cells of the intestinal lining that control what can pass from the gut into the bloodstream., and the immune cells beneath them. It lets nutrients and water through while keeping most bacteria and their products out¹. Permeability describes how easily substances pass through this barrier.

Permeability can increase for many reasons. Inflammatory and ulcerating gut diseases do it, and so do “stress” states such as endurance exercise, anti-inflammatory painkillers (NSAIDs), pregnancy and some food additives such as emulsifiers¹.

Does SIBO cause leaky gut?

The evidence suggests it can, at least in some people:

• A 1997 study cultured small-intestinal fluid from 34 people. Those with SIBO caused by colon-type bacteria had significantly higher permeability than controls, even when the lining looked normal under the microscope².
• A 1998 study of 70 adults found SIBO in 40. In one person with SIBO and abnormal liver tests, increased permeability and the liver tests both returned to normal after the SIBO was treated. Permeability was also increased in 3 of 6 others with the same type of overgrowth³.
• A 2009 study of 35 people with fatty liver disease found increased gut permeability, more SIBO and disrupted tight junctions in duodenal biopsies compared with healthy volunteers⁶.

Not every study agrees. In a 2009 study of 36 healthy older adults, intestinal permeability was similar in those with and without a positive SIBO breath test⁷. These are small studies using different methods, and they show an association more than a proven cause.

How SIBO might affect the barrier

• Bacterial contact. Exposure of the small intestine to bacteria triggers the release of zonulin, a protein that loosens tight junctions in laboratory and animal studies⁴.
• Damage to the lining. Overgrowth can reduce the activity of digestive enzymes such as lactase on the surface of the small intestine; in a 2025 pilot study, lactose digestion improved after SIBO treatment⁸. See our dairy guide.

Zonulin and leaky gut tests

Zonulin was discovered as a natural regulator of tight junctions; bacteria and gluten are the two known triggers of its release in the small intestine⁴. It is widely promoted as a blood or stool test for leaky gut. There are two problems:

• The common test may not measure zonulin. A 2018 study found that a widely used commercial zonulin test did not detect zonulin (pre-haptoglobin 2) at all, but other, related proteins such as properdin⁵.
• No permeability test is validated for clinical use. Research uses sugar-absorption tests (such as lactuloseLactulose A synthetic sugar the body cannot digest or absorb. As a breath-test substrate it travels the whole small intestine, which also makes false positives more likely. and mannitol), biopsies and other methods, but there are no validated clinical diagnostic tests for leaky gut¹.

See our guides to stool tests and blood tests for more on what these panels can and cannot show.

What to make of leaky gut claims

A 2019 review for clinicians in a major gastroenterology journal concludes that popular information about “healthy” or “leaky” gut needs confirmation before people adopt food exclusions, special foods or supplements to “repair” the gut. No disease has been cured by simply normalizing barrier function, there are no validated drug treatments, and it is unproven that restoring the barrier improves gut or whole-body diseases¹.

In practice, this means:

• Treat what can be diagnosed. If SIBO is confirmed, treating it and its underlying cause is the evidence-based approach. See our diagnosis guide and causes guide.
• Remove known barrier stressors where possible, such as regular NSAID use, with your doctor’s advice¹.
• Be cautious about expensive “gut repair” protocols and supplements sold on the basis of a zonulin result¹⁵.

Common questions

Is leaky gut a real condition?

Increased intestinal permeability is real and can be measured in research. It occurs in inflammatory gut diseases and in untreated celiac disease¹⁶. “Leaky gut syndrome” as a stand-alone diagnosis that explains a wide range of symptoms is not established¹.

Does treating SIBO fix leaky gut?

It may. In the 1998 study, increased permeability returned to normal after SIBO was treated³, but this has not been tested in a larger trial.

Should I get a zonulin test?

It is unlikely to help. The most widely used test may not measure zonulin⁵, and no permeability test is validated for diagnosis¹.