Presented at the 16^th International Celiac Disease Symposium (ICDS) in Prague, this study showed that researchers from Biomedal Life Science were able to identify whether or not a person has ingested gluten by detecting the presence of gluten immunogenic peptides (GIP) in urine. This is the first time a urine test has been used to monitor compliance with the gluten-free diet.

When gluten is digested in the body, it is broken down into smaller peptides, some of which are resistant to digestion by all individuals. These peptides also have immune-stimulating properties in individuals with celiac disease. These peptides, called gluten immunogenic peptides (GIPs), can already be detected accurately in food and are also what researchers looked for in this study in human urine samples.

The researchers showed they were able to detect GIPs in urine after consumption of as little as 50 mg of gluten, as early as 4-6 hours after gluten intake and up to 1-2 days afterwards. To help understand what 50 mg of gluten really looks like, we turned to Tricia Thompson, MS, RD, Founder of Gluten Free WatchDog, LLC.

“If you take a one-ounce slice of ‘regular’ white bread and break it into 7,030 pieces, each of these pieces contains 0.57 mg of gluten. You can think of this as just a crumb,” stated Thompson. This small amount is the minimum found to cause damage in celiac disease patients according to the landmark study of Catassi et al. in 2007. In other words, the urine test is able to detect the smallest amount of gluten that has been shown to damage the small intestine.

Researchers first started by testing this technique in a control group of individuals without celiac disease. This group had high GIP presence in their urine to start, and then when asked to go gluten-free, researchers saw the level of GIPs in the urine disappear. When this control group brought gluten back into their diet, the levels of GIPs returned again.

After proving that the detection technique could work, researchers moved to more of a “real life” situation, evaluating 58 patients with celiac disease in addition to 76 without celiac disease as a control group. As expected, the control group had high levels of GIPs in their urine. However, the group with celiac disease was not completely in the undetectable range as one would hope. In fact, more than 50% of the group with celiac disease had detectable GIPs in their urine. The researchers pointed to the fact that this continues to prove that complete compliance with the gluten-free diet is difficult to attain, and that voluntarily or involuntary consumption of gluten is common in patients on a gluten-free diet, reinforcing the need for a test such as this to monitor true compliance.

To show that these levels of GIPs in the urine are associated with intestinal damage in patients with celiac disease, a retrospective analysis was done looking at these patients’ biopsy results. Researchers report that they found a correlation between gluten in urine and damage in the gut. More than 80% of the patients with no detectable GIPs in their urine had no villous atrophy or relevant inflammation, while all the patients with higher levels of GIPs had higher degrees of damage in the intestinal mucosa.

This test could be a valuable product if and when it becomes commercially available. It is important to note that the test has not been approved by any regulatory agency and it remains a test only available for use in the research setting at this time.

Here are some real-life scenarios of how monitoring gluten ingestion through urine testing could benefit people with celiac disease and their doctors:

• Newly diagnosed patients who are getting used to the diet would have a tool to help monitor for accidental consumption of gluten
• When doctors suspect a person may not be strictly following a gluten-free diet, this would provide a direct way to prove the consumption, as opposed to a clinic visit alone or techniques that may take several weeks to show actual damage or evidence of gluten ingestion such as a blood test or invasive biopsy
• Patients who are either asymptomatic or non-responsive to the gluten-free diet would benefit considerably by being able to determine if actual ingestion is occurring
• All patients would gain a tool to allow them to detect accidental gluten ingestion from dining out, mislabeled food products or other similar scenarios, which could help empower them to make different choices in the future
• Patients would have an easy way to confirm that they are maintaining a strict gluten-free diet and their small intestine is likely healing, due to the finding that urine with no detectable GIP seems to be associated with having no villous atrophy or inflammation on biopsy

The same researchers from Biomedal Life Science have also developed a tool for the detection of GIPs in fecal samples, a test that is already available in some countries as a laboratory service for similar application. The study authors state that the urine test will be less sensitive than the fecal test but will be able to more quickly detect if gluten has been consumed. The stool test could help patients better manage their gluten-free diet by ultimately serving as a point of care tool either in the doctor’s office or at home. Biomedal is working to distribute the stool test in the U.S. in the near future, while the urine test is expected to take a few years.

*Authors: María de Lourdes Moreno¹, Ángel Cebolla², Alba Muñoz-Suano², Carolina Carrillo², Isabel Comino¹, Ángeles Pizarro³, Francisco León⁴, Alfonso Rodríguez- Herrera⁵ and Carolina Sousa¹

¹Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad de Sevilla, C/ Profesor García González S/N, 41012-Sevilla, Spain; ²Biomedal S.L., C/ Américo Vespucio 5, 41092- Sevilla, Spain; ³Unidad Clínica de Aparato Digestivo, Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot S/N, 41013-Sevilla, Spain; ⁴Celimmune, Bethesda, MD, USA; ⁵Unidad de Gastroenterología y Nutrición, Instituto Hispalense de Pediatría, C/ Guadalbullón S/N, 41013-Sevilla, Spain