Leaky gut, without the hype — what intestinal permeability really is

Few phrases in health divide opinion as quickly as “leaky gut.” To some people it explains everything: the fatigue, the joint aches, the skin, the food reactions, the brain fog. To others it is a sign that whoever is talking has stopped doing medicine. Patients arrive caught between the two, having read that it is either the root of all disease or entirely made up.

Neither is right. The gut lining does have a controlled, measurable permeability, and that permeability does change under identifiable conditions. What does not hold up is the idea that “leaky gut” is a diagnosis in itself, or that it can be fixed by a single powder. The useful version sits in between, and it starts with the physiology.

A barrier that is meant to open and close

The lining of the small intestine is a single layer of cells. It has an impossible job: let nutrients, water, and electrolytes through, while keeping out bacteria, bacterial fragments, and partially digested food proteins. It manages this with two routes. Nutrients are mostly taken up through the cells, which can be selective. The space between the cells is sealed by protein complexes called tight junctions — built from proteins such as occludin, the claudins, and zonula occludens — which act like adjustable gaskets.

Those gaskets are not fixed. They loosen and tighten in response to signals, and one of the better-studied signals is zonulin, a protein the gut releases when it encounters certain bacteria and gliadin, a component of gluten. Loosening the junctions briefly can be protective — it helps flush a threat. The trouble comes when the signals never switch off, and the space between cells stays more open than it should.

When that happens, material that would normally stay in the gut reaches the tissue underneath, where much of the body’s immune system is stationed. Bacterial fragments such as lipopolysaccharide can reach the bloodstream in small amounts. The immune system responds, and the result is low-grade inflammation that does not stay politely in the gut.

What loosens the barrier

Increased permeability almost always has a cause, and the causes are ordinary. The most common ones we look for:

• NSAIDs. Anti-inflammatory painkillers such as ibuprofen and naproxen are well known to irritate and increase permeability of the gut lining, particularly with regular use. If you take them for a reason, that is a conversation to have with your prescribing doctor, not something to stop on your own.
• Alcohol. Alcohol directly loosens tight junctions and alters the gut microbiome, and the two effects compound each other.
• Infections. Gastrointestinal infections, parasites, and overgrowths — including the small-intestine overgrowth described in our piece on SIBO — keep the lining in a defensive, inflamed state.
• Dysbiosis. The bacteria that produce butyrate, a short-chain fatty acid that is a primary fuel for the cells of the colon lining, help maintain the barrier. When those populations are low and inflammatory species are high, the barrier loses maintenance.
• Chronic stress. Stress hormones and the nervous system act on the gut wall directly, altering blood flow, mucus production, and junction tightness. The gut barrier is one of the places psychological stress becomes physical.
• Gluten, in some people. In celiac disease the link between gluten, zonulin, and permeability is well established. In people without celiac, the effect is less clear and varies.

A mechanism, not a diagnosis

This is the part the hype skips. Increased intestinal permeability describes how something is happening, not what is wrong or why. Saying someone has a leaky gut is like saying someone has a fever: true, possibly important, and incomplete until you know what is driving it.

Leaky gut is the middle of the story, not the end of it. The question that matters is what opened the barrier, and whether it is still happening.

That distinction changes treatment. If the driver is daily NSAID use, a gut-healing protocol without addressing it is working against the current. If the driver is an infection, the infection comes first. If it is dysbiosis after repeated antibiotics, the microbiome is the target. Patient care rather than disease care means looking at the person in front of us and asking which of these applies, instead of applying the same protocol to everyone with the same label.

The honest limits of testing

Measuring permeability directly is harder than many marketing claims suggest. The classic research method is a sugar absorption test, which compares how much of two different sugars — one that crosses through cells and one that can only slip between them — appears in the urine. It is informative in studies and less practical in routine care. Blood zonulin tests are widely sold, but questions have been raised about what some commercial zonulin assays actually detect, so we do not lean on a single zonulin number. Antibody panels against bacterial fragments and junction proteins exist and can add context, but none of them is a standalone answer.

In practice we are usually more interested in the drivers, which are often easier to measure than the leak itself. A comprehensive stool panel can show infections, overgrowth, low beneficial bacteria, markers of inflammation such as calprotectin, secretory IgA as a read on the gut’s immune defense, and markers of digestive function. The detail on reading one is in what a stool test actually shows. Combined with a careful history, that usually tells us more about what to do than a permeability score alone.

Food sensitivity and autoimmunity, stated carefully

Two links come up constantly, and both deserve precision.

Food sensitivity. When the barrier is more open, food proteins reach the immune system in larger fragments and larger amounts than usual, and the immune system is more likely to react to them. This is one reason a food sensitivity panel full of reactions to the foods a person eats most often tends to point back to the gut rather than to a dozen separate problems with individual foods.

Autoimmunity. Increased permeability is a recognized part of the mechanism in celiac disease, and it has been observed alongside a number of other autoimmune conditions. What is not settled is the direction of cause in each case — whether permeability helps drive the autoimmune process, results from it, or both. It is reasonable to consider gut health as one piece of a broader plan for someone with autoimmune disease. It is not reasonable to promise that fixing the gut will reverse an autoimmune condition.

What repair actually involves

Repair follows an order, and the order matters more than any single product.

• Remove the drivers. Treat infections and overgrowth, reduce alcohol, and address medications that irritate the lining together with your prescribing doctor. Without this step, everything else is maintenance on a leaking pipe.
• Restore digestion upstream. Adequate stomach acid, enzymes, and bile mean food arrives in the small intestine properly broken down, which reduces the load on the lining.
• Feed the lining and the microbiome. A varied diet with enough fiber and plant diversity supports the bacteria that produce butyrate. Specific nutrients that support the lining — such as zinc, glutamine, and vitamin A and D status — are chosen based on what testing and history show, not stacked by default.
• Calm the nervous system. Acupuncture shifts autonomic tone toward rest-and-digest, which directly affects blood flow and repair in the gut wall. In Chinese medicine the Spleen governs transformation and transport — turning food into usable Qi and moving it where it needs to go — and a weakened Spleen pattern with dampness is often how this presentation reads. We treat that pattern alongside the functional work, not instead of it.

Where we start

If you have been told you have a leaky gut, or suspect you do, the first step is not a supplement. It is finding out what is putting pressure on the barrier — through a detailed history and, where it adds something, stool testing — and then taking those drivers away in a sensible order. That is how functional medicine approaches the gut. If you would like to start there, get in touch.

The journal is written by Dr. Nazzar from the practice. Articles reflect clinical observation and current research, not personalized medical advice. To explore your own case, schedule a consultation.