How gluten immunogenic peptide testing fits into coeliac care pathways
How gluten immunogenic peptide testing fits into coeliac care pathways
In our previous blog, Ángel Cebolla, CEO of Biomedal SL, discussed how Gluten Immunogenic Peptide (GIP) tests provide an objective way to detect gluten exposure in patients with coeliac disease. For clinicians managing these patients, this raises the question: how can GIP testing be integrated into everyday care pathways? Many clinicians are asking this question as they begin to explore how GIP testing can support diagnosis, follow-up and dietary counselling. In this blog, Ángel summarises how GIP detection is recommended in Spanish guidelines to help clinicians monitor dietary adherence and guide more targeted interventions.
GIP testing for monitoring gluten-free diet adherence
One of the key challenges in managing coeliac disease is assessing whether patients are truly adhering to a gluten-free diet. Symptoms alone are unreliable, dietary questionnaires are subjective and negative serological markers do not predict mucosal damage in the follow up of coeliac disease, but this is where GIP testing can provide valuable insight. GIPs are fragments of gluten that resist digestion and can be detected in urine or stool very soon after gluten ingestion. They originate directly from gluten, so their presence provides evidence of recent dietary exposure. In practice, GIP testing allows clinicians to rely on more objective measures of gluten ingestion, rather than questionnaires and symptomology alone.
Understanding your coeliac patients
Coeliac patients tend to fall into three broad behavioural patterns when monitored using GIP detection, and understanding these categories can determine how best to use the tests. Firstly, there are patients with excellent adherence, who consistently test negative for GIP and appear to follow the gluten-free diet carefully. The second group can be described as ‘in progression’, these patients are attempting to follow the gluten-free diet but show intermittent positivity when tested. In other words, GIP testing reveals occasional gluten exposure that may result from accidental contamination, hidden ingredients or misunderstandings about dietary restrictions. The third group consists of patients who do not adhere to the diet at all (10-20 per cent of the coeliac population) . In these individuals, GIPs are detected frequently (>60 per cent of the tests), indicating repeated gluten ingestion.
This categorisation has important clinical implications, as higher rates of GIP positivity correlate with a greater likelihood of persistent villous atrophy;1 put simply, patients with more frequent detection of GIPs are more likely to have ongoing intestinal damage. Understanding which group a patient belongs to allows clinicians to tailor their approach. Some patients may simply need reassurance and routine follow-up, while others may benefit from more intensive dietary counselling or investigation.
Where GIP testing fits into clinical care
Several practical use cases for GIP testing exist and they fall into a three-phase strategy, including urgent use cases, follow-up for newly diagnosed patients and diagnostic support.
Phase one: non-responding coeliac disease patients
The first and perhaps most urgent application is in patients with non-responsive coeliac disease, who are symptomatic with positive serology and have followed a gluten-free diet for at least two years. Detecting GIP can help to determine whether patients who continue to experience symptoms despite believing they have followed a gluten-free diet have in fact been exposed to gluten, or whether it is another disease. Confirmation of exposure to gluten allows clinicians to shift their focus towards identifying dietary sources of contamination and ensuring the patient understands the severe implications of exposure.
Similarly, GIP testing may be useful in patients who remain symptomatic or those who continue to have positive serology after two or more years on a gluten-free diet. In these situations, clinicians can use GIP to differentiate between ongoing gluten ingestion and other potential causes of persistent symptoms.
Phase two: follow-up for newly diagnosed patients
Another valuable role GIP testing plays is during the early follow-up period after diagnosis. Incorporating GIP testing into patient visits allows clinicians to directly assess whether gluten exposure is still occurring. Objective monitoring like this can really help to guide conversations between clinicians, dietitians and patients, leading to targeted dietary counselling that becomes far more effective when patients can work out the source of their exposure.
Phase three: diagnostic support
Another interesting application relates to diagnosis itself. It is not uncommon for patients to reduce or eliminate gluten from their diet before undergoing diagnostic evaluation but this can hinder diagnosis because serology and biopsy both depend on sufficient gluten exposure to trigger detectable immune responses. Detecting GIP can help to confirm that gluten has been consumed before testing, reducing the risk of false negative diagnostic results.
GIP testing recommendations
The Spanish Society for Coeliac Disease guidelines published in 2024 address this final phase directly, including GIP testing as a standardised follow-up for patients.2 The guidelines recommend that a urine or stool sample is taken prior to duodenal biopsy to ensure accurate histological interpretation, by verifying that the patient has ingested gluten before diagnosis. After diagnosis, patients can continue to be monitored using GIP testing every 3-6 months, which helps to differentiate true adherence from partial gluten intake. Then, patients on long term follow-up should undergo annual or semi-annual monitoring. Evidence shows that having more than four urine positive GIP tests in a year predicts villous atrophy with a specificity of 93 per cent.3
Interpreting GIP test results
The next question for clinicians is how to interpret the results of GIP testing in everyday practice (Figure 1). If the test is negative and the patient is clinically well, this is reassuring and all that’s required is routine follow-up and ongoing dietary support. However, if the test is negative but symptoms persist, clinicians should consider alternative explanations, such as small intestinal bacterial overgrowth (SIBO), FODMAP intolerance or other enteropathies. Persistently positive GIP tests require more intervention, which may involve comprehensive dietary counselling and exploring whether the issue relates to accidental exposure, gaps in patient education or motivational challenges.
Growing adoption and future directions
In all three of these scenarios, GIP testing is showing real potential for giving clinicians valuable information about their coeliac patients and dietary adherence. Its clinical use is expanding rapidly in Europe – it is already used in more than 40 hospitals in Spain – and interest is also increasing internationally with clinical trials and research groups exploring its role in both clinical practice and patient self-monitoring. While further research is ongoing, the available evidence suggests that GIP testing provides a practical, non-invasive method for identifying gluten exposure.
Click here to find out more about GIP tests.
References
- Ruiz-Carnicer, Á et al. (2020) Negative predictive value of the repeated absence of gluten immunogenic peptides in the urine of treated celiac patients in predicting mucosal healing: new proposals for follow-up in celiac disease. 112(5):1240-1251.
- (2024). Evaluación de la adherencia a la dieta sin gluten en pacientes adolescentes y adultos con enfermedad celiaca: estrategia de manejo de los péptidos inmunogénicos del gluten. Accessed 12th of March 2026. https://seec.es/wp-content/uploads/2024/02/Protocolo-SEEC-GIP.pdf
- Garzón-Benavides M, et al. (2023) Clinical utility of urinary gluten immunogenic peptides in the follow-up of patients with coeliac disease. Aliment Pharmacol Ther. 57(9):993-1003. doi:10.1111/apt.17417
