How to test for leaky gut

How to Test for Leaky Gut, and Why Zonulin Is the Wrong Test

Leaky gut is tested with a physician-ordered sugar permeability test: you drink sugars of two sizes, then collect urine over timed windows, with labeled mannitol and each sugar read separately. The mail-order zonulin blood kit is the wrong test.

A zonulin number on a printout feels like an answer. It is not a measurement of your gut wall, and the harm that follows a leak shows up in numbers most people never get.

If you are trying to work out how to test for leaky gut, the zonulin test is probably the first thing you found. It arrives by mail, it prints one number, and people rebuild their whole diet around it. Chapter 4 of The Angry Gut by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Ami Michelle Grimes, told in the video above, lands somewhere sharper than either side of that fight: the wall is real, its failure can be measured, and the kit most people order does not measure it.

Dr. Padda is candid that his training taught him to wave these printouts away. He dropped the habit after reading a study in which a leaking wall, measured properly in healthy people, showed up years before disease did.

What a zonulin result is really reporting

Picture the lining of your gut as a wall one cell thick. It is the outer surface of the first brain, the gut, which stays in constant conversation with the second brain inside your skull. The mortar between its cells is sealed by proteins called claudins. When that seal loosens, fragments of gut bacteria slip into the blood, and metaflammation, the low and steady metabolic inflammation behind so much chronic disease, has a place to start.

Zonulin was meant to be a blood readout of that seal. The trouble is the assay. Zonulin was defined as a single protein, pre-haptoglobin-2, which some people’s genes do not let them make. When researchers compared the most widely used commercial kit with each person’s genotype, the kit reported the protein in people who cannot produce it, and it failed to detect the purified protein at all. What it seems to bind is properdin, an unrelated immune protein. A second research group ran two other commercial kits and found haptoglobin and a complement protein on the other end of the antibody.

The decisive comparison put serum zonulin next to a direct permeability test in the same people, healthy relatives of patients with Crohn’s disease. The correlation was r2 = 0.004.

How to test for leaky gut: what a real permeability test involves

You test a wall by seeing what gets across. For a permeability test, you drink sugars of two different sizes, then collect urine during set time windows. A small sugar slips through a healthy lining; a large one mostly should not. The early window reflects the small bowel and the late window reflects the colon. A physician orders it, and it is a timed urine collection rather than a blood kit.

Three details decide whether it can be trusted:

• Labeled mannitol. Everyday mannitol comes from food. In the study that validated the test, it was already in the urine of all 60 healthy volunteers before anyone swallowed a dose.
• Each sugar read separately. In people with inflammatory bowel disease, the two sugars measured one at a time separated patients from healthy volunteers. The ratio between them, the figure most reports print, found no difference.
• A second look before any verdict. People differ enormously on this test. In one group of 39 healthy young adults, 14 landed on the abnormal side of a common cutoff.

Measured this way, the result carries weight. Healthy relatives of people with Crohn’s disease, 1,420 of them, were tested and then followed for a median of 7.8 years. An abnormal baseline result came with roughly triple the risk of a later Crohn’s diagnosis, a hazard ratio of 3.03. That group carried strong family risk for one disease. A leaking wall is a finding worth acting on, not a sentence.

What can cause a leaky gut in an ordinary week?

The exposures shown to loosen the human gut lining are mostly things people do on purpose. One anti-inflammatory tablet more than doubled small-bowel leakiness in people with healthy guts, and a public speech raised it as well. One evening of heavy drinking pushed blood endotoxin up within 30 minutes. Raising core temperature two degrees, with no exercise, opened the small bowel in younger and older adults alike.

Behind that list sits a system problem. A bottle of anti-inflammatories on the shelf is quicker to reach than a workup for why the pain keeps returning, and short, crowded appointments reward the refill over the question. If you take one every day, do not stop on your own. Ask your physician what it is covering and whether that cause has ever been traced.

Is a leaky gut dangerous?

Endotoxin is a piece of the outer coat of certain gut bacteria, and your immune system reads it as an invasion. When healthy volunteers were given a small intravenous dose, their insulin sensitivity dropped 35% within a day, even though the pancreas kept producing insulin normally. Over ten years in 7,169 adults, people in the top quarter of endotoxin activity had 52% more risk of developing diabetes than people in the bottom quarter.

Here is the detail most leaky gut advice skips. After a 910-calorie fast-food meal, endotoxin in the blood rose and the inflammatory switches inside white blood cells turned on. C-reactive protein, the inflammation test most clinics order, did not budge.

Body size is a poor guide as well. In a study of women in The Gambia that measured endotoxin by mass spectrometry, levels were 57% higher in women with obesity and diabetes, yet no different between women with obesity and women without it. The gradient followed diabetes, not weight. The numbers worth having after a leak are metabolic, not the bathroom scale.

What Measura measures here, and what it does not

Measura [Cardiometabolic and Autonomic Health Analysis] does not offer zonulin or intestinal permeability testing. If your physician decides a permeability test is worth doing, the timed sugar collection is arranged elsewhere, with labeled mannitol.

What Measura can measure is the terrain a leaking wall acts on:

• Laboratory panels, chosen with your physician, can include markers of glucose, insulin, lipids and inflammation. Falling insulin sensitivity shows up there long before a diabetes diagnosis, as insulin resistance and metabolic health explains.
• Bioimpedance body composition separates fat mass from muscle and water instead of reporting one weight. When harm tracks metabolic state rather than size, that split matters, which is the point of body composition, not BMI.

Every result goes to your physician. Measura measures; it does not diagnose leaky gut or treat it.

Questions to bring to your physician

• Is a permeability test reasonable for me, and would it use labeled mannitol?
• Would the report show each sugar separately, not only the ratio?
• If my result sits near the cutoff, can we repeat it before I change what I eat?
• What would we do differently because of the zonulin number I already have?
• Can we measure my insulin sensitivity and body composition to see whether anything that crossed has left a mark?

How the first brain signals the second brain is traced in the previous post on the vagus nerve, and everything that crosses the wall reaches the liver first, which is where the next post on an echogenic liver picks up. Every study above, including the results that cut against the argument, is laid out in the Chapter 4 book companion. Unmeasured is unmanaged: a wall can be closed, and what it let through can be tracked.

Frequently asked questions

Is the zonulin test accurate for leaky gut?

Not as a measure of the gut wall. Kits sold as zonulin tests failed validation in two separate laboratories, and neither check found the protein printed on the label. When serum zonulin and a direct sugar test were run side by side in the same people, the two did not correlate. Why one number rarely settles a question is covered in what a test result can and cannot tell you.

What does a high zonulin level mean?

It means the kit detected something that tends to rise with obesity, diabetes, and glucose and lipid markers. It does not mean your gut wall is breached, and it is not a reason on its own to remove foods. If metabolic trouble is what the number hints at, measuring insulin and body composition answers that directly. For reading any flagged value, see understanding your results.

Can a healthy person get an abnormal leaky gut result?

Yes. People vary widely on sugar permeability tests, and the usual cutoffs sit close to normal. In one group of healthy young adults, more than a third landed on the abnormal side of the line. A borderline result calls for a repeat under controlled conditions before any change in diet. How repeat testing is usually planned is explained in how often to repeat testing.

Does Measura test for leaky gut?

No. Zonulin and intestinal permeability tests are not part of the Measura library; a permeability test is a timed urine collection your physician arranges elsewhere. Measura measures the metabolic and body composition picture a leaking wall can affect, and every finding goes to your physician. For the full list, read what Measura actually measures.

Can a leaky gut cause insulin resistance?

The mechanism has been shown in people. Healthy volunteers given a small dose of bacterial endotoxin lost about a third of their insulin sensitivity within a day, and over a decade higher endotoxin activity tracked with new diabetes. That does not prove a leak is behind any one person’s insulin resistance, but it is a reason to measure it. See insulin resistance before diabetes.

Does leaky gut show in bloodwork?

Not directly. The mail-order zonulin blood kit failed validation in two laboratories, and in the same people it did not correlate with a direct sugar test. The wall itself is tested with a physician-ordered timed urine collection. Bloodwork is where the harm shows: falling insulin sensitivity and glucose and lipid markers. C-reactive protein, the usual inflammation test, did not move after a fast-food meal raised endotoxin.

What are the markers for a leaky gut?

The direct marker is how much of each swallowed sugar reaches the urine during set time windows; the early window reflects the small bowel and the late window the colon. Each sugar should be read separately, with labeled mannitol, because the ratio most reports print missed the difference. The downstream markers are metabolic: insulin sensitivity and body composition show whether anything that crossed has left a mark.

References

• Scheffler, L., Crane, A., Heyne, H., Tonjes, A., Schleinitz, D., Ihling, C. H., Stumvoll, M., Freire, R., Fiorentino, M., Fasano, A., Kovacs, P., & Heiker, J. T. (2018). Widely used commercial ELISA does not detect precursor of haptoglobin2, but recognizes properdin as a potential second member of the zonulin family. Frontiers in Endocrinology, 9, 22. https://doi.org/10.3389/fendo.2018.00022
• Ajamian, M., Steer, D., Rosella, G., & Gibson, P. R. (2019). Serum zonulin as a marker of intestinal mucosal barrier function: May not be what it seems. PLoS One, 14(1), e0210728. https://doi.org/10.1371/journal.pone.0210728
• Power, N., Turpin, W., Espin-Garcia, O., Smith, M. I., CCC GEM Project Research Consortium, & Croitoru, K. (2021). Serum zonulin measured by commercial kit fails to correlate with physiologic measures of altered gut permeability in first degree relatives of Crohn’s disease patients. Frontiers in Physiology, 12, 645303. https://doi.org/10.3389/fphys.2021.645303
• Khoshbin, K., Khanna, L., Maselli, D., Atieh, J., Breen-Lyles, M., Arndt, K., Rhoten, D., Dyer, R. B., Singh, R. J., Nayar, S., Bjerkness, S., Harmsen, W. S., Busciglio, I., & Camilleri, M. (2021). Development and validation of test for “leaky gut” small intestinal and colonic permeability using sugars in healthy adults. Gastroenterology, 161(2), 463–475.e13. https://doi.org/10.1053/j.gastro.2021.04.020
• Turpin, W., Lee, S.-H., Raygoza Garay, J. A., Madsen, K. L., Meddings, J. B., Bedrani, L., Power, N., Espin-Garcia, O., Xu, W., Smith, M. I., Griffiths, A. M., Moayyedi, P., Turner, D., Seidman, E. G., Steinhart, A. H., Marshall, J. K., Jacobson, K., Mack, D., Huynh, H., … Croitoru, K. (2020). Increased intestinal permeability is associated with later development of Crohn’s disease. Gastroenterology, 159(6), 2092–2100.e5. https://doi.org/10.1053/j.gastro.2020.08.005
• Vanuytsel, T., van Wanrooy, S., Vanheel, H., Vanormelingen, C., Verschueren, S., Houben, E., Salim Rasoel, S., Toth, J., Holvoet, L., Farre, R., Van Oudenhove, L., Boeckxstaens, G., Verbeke, K., & Tack, J. (2014). Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut, 63(8), 1293–1299. https://doi.org/10.1136/gutjnl-2013-305690
• Mehta, N. N., McGillicuddy, F. C., Anderson, P. D., Hinkle, C. C., Shah, R., Pruscino, L., Tabita-Martinez, J., Sellers, K. F., Rickels, M. R., & Reilly, M. P. (2010). Experimental endotoxemia induces adipose inflammation and insulin resistance in humans. Diabetes, 59(1), 172–181. https://doi.org/10.2337/db09-0367
• Pussinen, P. J., Havulinna, A. S., Lehto, M., Sundvall, J., & Salomaa, V. (2011). Endotoxemia is associated with an increased risk of incident diabetes. Diabetes Care, 34(2), 392–397. https://doi.org/10.2337/dc10-1676
• Ghanim, H., Abuaysheh, S., Sia, C. L., Korzeniewski, K., Chaudhuri, A., Fernandez-Real, J. M., & Dandona, P. (2009). Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: Implications for insulin resistance. Diabetes Care, 32(12), 2281–2287. https://doi.org/10.2337/dc09-0979
• Jobe, M., Agbla, S. C., Todorcevic, M., Darboe, B., Danso, E., Pais de Barros, J.-P., Lagrost, L., Karpe, F., & Prentice, A. M. (2022). Possible mediators of metabolic endotoxemia in women with obesity and women with obesity-diabetes in The Gambia. International Journal of Obesity, 46(10), 1892–1900. https://doi.org/10.1038/s41366-022-01193-1

Related reading

• Vagus Nerve and Anxiety: What a Heart Reading Shows About Your Gut
• What Does Echogenic Liver Mean? Reading the Numbers Behind the Scan
• Laboratory Panels

Medically reviewed by Dr. Gurpreet Singh Padda, MD, MBA, MHP, medical director of Measura. Last reviewed September 12, 2026.