What Is Leaky Gut? Intestinal Permeability Explained by an Herbalist
Leaky gut is the everyday name for increased intestinal permeability, a measurable loosening of the barrier that lines the small intestine. When the junctions between intestinal cells open wider than normal, molecules that would usually stay in the gut can pass into the bloodstream. Researchers can measure this in people. What remains unsettled is whether it causes disease on its own or mostly appears alongside other conditions.
Key takeaways
- Intestinal permeability is a real, measurable property of the gut lining. "Leaky gut syndrome" as a standalone diagnosis is not recognized in gastroenterology.
- Gliadin from wheat, psychological stress, alcohol, and NSAID painkillers have each raised permeability in controlled human studies.
- Glyphosate residue is well documented on North American wheat, but its effect on the human gut barrier has not been demonstrated.
- The validated test is a urine sugar ratio after drinking lactulose and mannitol. At-home blood zonulin tests are not validated.
- One randomized trial found glutamine lowered permeability in post-infection IBS. Bone broth and most probiotics have no permeability trials behind them.
I am a certified clinical herbalist, not a physician. This article is educational. Persistent digestive symptoms deserve a proper workup, since several conditions with the same symptoms are diagnosable and treatable.
What leaky gut means
Evidence: one clinical review in Gut, 2019, written for gastroenterologists.
The intestinal lining is a single layer of cells sealed together by protein complexes called tight junctions. A mucus layer sits on top and immune cells sit underneath. Together they let water and nutrients through while blocking bacteria, bacterial fragments, and partly digested food. Permeability rises when tight junctions loosen, when cells die faster than they are replaced, or when material passes directly through the cells.1
Michael Camilleri's 2019 review at Mayo Clinic makes two points that frame everything below. Increased permeability is documented in celiac disease, Crohn's disease, and a set of non-inflammatory conditions he calls stressed states, including irritable bowel syndrome. At the same time, he writes that public claims about healthy or leaky gut need confirmation before anyone endorses food exclusions or supplements to repair the barrier.1 Both statements are true at once, and the rest of this article stays inside them.
Symptoms people associate with leaky gut
Evidence: patient reports and overlap with diagnosed conditions. No validated symptom set exists.
People who describe themselves as having leaky gut most often report bloating, gas, loose stools, new food reactions, fatigue, joint aches, skin flares, and low mood. Every one of these also appears in irritable bowel syndrome, inflammatory bowel disease, celiac disease, small intestinal bacterial overgrowth, and thyroid disorders. Because the overlap is complete, symptoms alone cannot tell you whether your barrier is more permeable than normal. The section on testing covers what can.
What raises intestinal permeability
Evidence: human tissue and human volunteer studies for gliadin, stress, alcohol, and NSAIDs. Animal and review data only for glyphosate.
Gliadin from wheat
Gliadin is the fraction of gluten that triggers the release of zonulin, a protein that signals tight junctions to open. In 2015, Alessio Fasano's group exposed living duodenal biopsy tissue to gliadin and measured electrical resistance across the lining, which drops as permeability rises. Tissue from all four groups responded: six people with active celiac disease, six with celiac in remission, six with non-celiac gluten sensitivity, and five controls with neither.2 The response was largest in active celiac disease and in gluten sensitivity. The sample was small and the exposure happened in a dish, so the study shows a mechanism rather than what a slice of bread does over a lifetime. It is the basis for the claim that gluten opens tight junctions in everyone, and that claim should be stated with the study's limits attached. If you suspect celiac disease, testing has to happen while you are still eating gluten, since antibody tests turn negative on a gluten-free diet.
Glyphosate residue
Glyphosate is sprayed on some North American wheat, oats, and legumes shortly before harvest to dry the crop evenly, a practice called desiccation that is common where growing seasons are short.5 A 2020 review from the University of British Columbia examined whether the residue could explain rising wheat intolerance by disrupting gut bacteria. Its conclusion was careful. Commensal bacteria are more sensitive to glyphosate than opportunistic pathogens in laboratory tests, which makes dysbiosis plausible, but the authors state that methodological weaknesses across the literature make it impossible to draw definitive conclusions about human health.5 A 2021 rat study led from King's College London then confirmed the mechanism: glyphosate at regulator-approved doses inhibited the shikimate pathway in gut bacteria and shifted the microbiome.6 No human study has measured intestinal permeability after dietary glyphosate exposure.
The cancer question is separate from the gut question. In 2015 the International Agency for Research on Cancer classified glyphosate as Group 2A, probably carcinogenic to humans, based on limited human evidence for non-Hodgkin lymphoma and sufficient evidence in animals.3 On February 17, 2026, Monsanto announced a proposed class settlement funded at up to $7.25 billion to resolve current and future Roundup claims alleging non-Hodgkin lymphoma. The same release states that the settlement contains no admission of liability and that the U.S. EPA and EU regulators continue to conclude glyphosate is not carcinogenic.4 I buy organic or European wheat products for my own kitchen because the desiccation practice is documented and the residue is avoidable at low cost. That is a personal purchasing decision, not a health claim.
Psychological stress
A 2014 study at the University of Leuven asked 23 healthy volunteers to give a public speech, then measured small intestinal permeability with a lactulose-mannitol urine test. Permeability rose only in the participants whose salivary cortisol also rose. Injecting corticotropin-releasing hormone reproduced the effect, and a mast cell stabilizer blocked it.7 This is the clearest human evidence that stress hormones act directly on the gut barrier, and it explains why digestive symptoms so often track with hard periods of life.
Alcohol and NSAID painkillers
The Leuven study used indomethacin, a non-steroidal anti-inflammatory drug, as its positive control because NSAIDs reliably raise permeability, and it more than doubled the lactulose-mannitol ratio.7 For alcohol, a 1984 Lancet study measured chromium-EDTA absorption in 36 alcoholic patients without liver disease. Those who had stopped drinking fewer than four days earlier almost always had higher permeability than controls, and in many the abnormality lasted up to two weeks after their last drink.8 The study population was heavy drinkers, so it does not tell you what an occasional glass of wine does.
How intestinal permeability is measured
Evidence: methods described in the 2019 Gut review.
The validated method is a probe test. You drink a solution of two sugars, usually lactulose and mannitol, then collect urine for two to five hours. Mannitol is small and crosses the lining normally, while lactulose is larger and should mostly be excluded. A high lactulose-to-mannitol ratio means more of the large molecule got through.1 Research centers run this test, and a few functional medicine labs offer a mail-in version, although reference ranges vary between labs.
Most products marketed as at-home leaky gut tests measure zonulin in blood or stool. Camilleri's review notes that the commercial zonulin assays have not been shown to measure zonulin specifically, and that serum results have not been validated against the probe test.1 A high zonulin result on a finger-prick kit is not evidence of a permeable gut, and a normal one is not evidence against it.
How conventional medicine approaches it
Evidence: the 2019 Gut review, plus my own experience as a patient.
Gastroenterology does not treat leaky gut as a diagnosis. Increased permeability is documented within celiac disease, inflammatory bowel disease, and irritable bowel syndrome, and is investigated as part of those conditions.1 A typical workup rules out celiac disease, checks for inflammation, and may trial a low-FODMAP diet for symptom control. That approach helps many people, and it is also where I stalled. After two years of symptoms, normal labs, and a diet reduced to a handful of tolerated foods, I was diagnosed with IBD and told to manage it long term. Working with a holistic herbalist and a practitioner of traditional Chinese medicine was the turn where I started improving, and that experience is why this site exists. The full story is on the about page.
Diet and support with some evidence behind them
Evidence: one randomized controlled trial for glutamine. Everything else is mechanism, tradition, or clinical experience.
Glutamine
Glutamine is the amino acid that intestinal cells use for fuel. In an 8-week randomized, double-blind trial at Tulane, 106 adults with post-infection IBS-D and elevated permeability took either 5 grams of glutamine three times daily or placebo. Symptom scores fell by at least 50 points in 80 percent of the glutamine group against 6 percent on placebo, and permeability normalized in the glutamine group.9 The participants all had a documented infection as their trigger, so the result does not automatically transfer to people whose symptoms began differently.
Probiotics and fermented foods
Probiotic trials in IBS have measured symptoms far more often than permeability, and results vary by strain. The Gut review lists probiotics and fermented foods among the interventions that need confirmation before being recommended for barrier repair.1 I use raw dairy and traditionally fermented vegetables in my own kitchen for their live cultures, and I would describe that as a food choice rather than a treatment.
Bone broth
Bone broth supplies glycine, proline, and gelatin, which are structural components of connective tissue. No human trial has measured intestinal permeability before and after bone broth. It is a digestible, mineral-rich food that many people with digestive symptoms tolerate well, and that is the extent of what can be said.
The food-first pattern I use with clients
Cooked rather than raw vegetables, well-cooked meat and fish, ripe fruit, dairy if tolerated, and a full removal of industrial seed oils and ultra-processed foods. Wheat comes out for a trial period, with the celiac test done first. Alcohol and NSAIDs come out for the same period because both are shown above to raise permeability directly. Sleep and stress get equal weight with food, since the Leuven data shows cortisol acts on the barrier within hours.7 The full version, with timing and reintroduction, is in the Gut Repair Protocol, and related articles are collected on the gut health hub.
Frequently asked questions
Is leaky gut real?
Increased intestinal permeability is real and can be measured with a lactulose-mannitol urine test. What is not established is "leaky gut syndrome" as a single condition that causes fatigue, joint pain, or mood changes on its own. Permeability is documented within celiac disease, IBD, and IBS, and researchers are still working out whether it is a cause or a consequence.1
How do you test for leaky gut at home?
A few labs will mail a lactulose-mannitol kit where you drink the sugar solution and return a urine sample. That is the validated method. Blood or stool zonulin kits sold online have not been validated against the probe test and should not be used to confirm or rule out a permeable gut.1
What is the difference between celiac disease and leaky gut?
Celiac disease is an autoimmune condition with a defined diagnosis, a blood test, and a biopsy. Increased permeability is one of its features. Leaky gut is a description of the barrier, not a diagnosis, and it can appear with or without celiac disease. If wheat causes symptoms, get tested for celiac disease before removing it, because the test requires ongoing gluten exposure to be accurate.
How long does it take for permeability to change?
The stress study measured a rise within two hours of a public speech, and the alcohol study found elevation lasting up to two weeks after drinking stopped.78 The glutamine trial ran eight weeks. For diet changes, most practitioners work in blocks of six to twelve weeks before reassessing.
Sources
- Camilleri M. Leaky gut: mechanisms, measurement and clinical implications in humans. Gut. 2019;68(8):1516-1526. doi:10.1136/gutjnl-2019-318427. PMID 31076401. ↩
- Hollon J, Puppa EL, Greenwald B, Goldberg E, Guerrerio A, Fasano A. Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. Nutrients. 2015;7(3):1565-1576. doi:10.3390/nu7031565. PMID 25734566. ↩
- International Agency for Research on Cancer. IARC Monographs Volume 112: evaluation of five organophosphate insecticides and herbicides. Press summary, 20 March 2015. iarc.who.int (PDF). ↩
- Bayer AG. Monsanto announces Roundup class settlement agreement to resolve current and future claims. Press release, 17 February 2026. bayer.com. Company-authored source; positions on safety are the company's. ↩
- Barnett JA, Gibson DL. Separating the empirical wheat from the pseudoscientific chaff: a critical review of the literature surrounding glyphosate, dysbiosis and wheat-sensitivity. Front Microbiol. 2020;11:556729. doi:10.3389/fmicb.2020.556729. PMC7545723. ↩
- Mesnage R, Teixeira M, Mandrioli D, et al. Use of shotgun metagenomics and metabolomics to evaluate the impact of glyphosate or Roundup MON 52276 on the gut microbiota and serum metabolome of Sprague-Dawley rats. Environ Health Perspect. 2021;129(1):017005. doi:10.1289/EHP6990. PMID 33502259. Rat study. ↩
- Vanuytsel T, van Wanrooy S, Vanheel H, et al. Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut. 2014;63(8):1293-1299. doi:10.1136/gutjnl-2013-305690. PMID 24153250. ↩
- Bjarnason I, Peters TJ, Wise RJ. The leaky gut of alcoholism: possible route of entry for toxic compounds. Lancet. 1984;1(8370):179-182. doi:10.1016/s0140-6736(84)92109-3. PMID 6141332. ↩
- Zhou Q, Verne ML, Fields JZ, et al. Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome. Gut. 2019;68(6):996-1002. PMID 30108163. Competing interests: none declared. ↩
