Written by Francisco Leon, MD, PhD, Chief Scientific Officer, Co-Founder, Provention Bio

Current guidelines recommend routine follow-up for celiac disease with dietary interviews and celiac blood tests, though these methods are not accurate measures of gluten-free diet (GFD) adherence. A recent study in Spain tested the use of gluten immunogenic peptides (GIP)—a direct measure of gluten intake—in stool samples to determine its usefulness in accurately monitoring GFD adherence. The researchers found that measuring GIP in stool is helpful for monitoring GFD adherence, and it could reduce the need for additional invasive tests for follow‐up after a celiac disease diagnosis.

Children are generally thought to recover more completely than adult celiac patients once they start the GFD. However, several studies have shown that up to 1 in 5 children with celiac disease on the GFD have persistent gut damage despite being on the GFD for at least 1 year.

While experts agree that strict adherence to the GFD is crucial for the health of people with celiac disease, until recently, there have been no direct methods to assess adherence to the GFD. Dietary interviews, blood tests, and monitoring symptoms do not fully correlate with gluten ingestion—meaning they are not always able to detect gluten in the diet accurately.

A detailed dietary history is time-consuming and requires the collaboration of a dietitian, so physicians often rely upon the patient’s own assessment of diet adherence. Even a thorough review of eating habits may fail to find accidental gluten ingestions, which can cause a lack of gut recovery in some people with celiac disease.

Symptoms alone are also a poor measure of diet adherence. Many patients present minimal or no symptoms at diagnosis. Even after a gluten challenge causing intestinal damage, as many as 1 in 5 still show no related symptoms.1  When patients do have symptoms, these may be caused by coexisting disorders with similar symptoms, such as irritable bowel syndrome, microscopic colitis, or pancreatic disease.

Anti-tissue transglutaminase (tTG) blood tests, validated for the diagnosis of celiac disease, are also used in the monitoring of the disease, despite their low sensitivity in the detection of persistent gut damage.2,3

Finally, while small bowel biopsy is considered the gold standard for assessment of celiac disease activity, it is not specific and it has high variability. The European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) advises against regular re‐biopsy in children on the GFD, due to unnecessary risks, negative impacts on quality of life, and unnecessary medical costs.4

The detection of GIP in stool and urine has recently emerged as a useful technique to detect unintentional gluten ingestion. Unlike traditional methods to monitor GFD adherence, which only evaluate some of the consequences of GFD transgressions, this non‐invasive method enables a direct and quantitative assessment of gluten exposure.2,5 With these novel GIP methods, it has been shown that compliance with the GFD decreases on long-term follow‐up.2

In this study, Comino and collaborators evaluated the usefulness of stool GIP to monitor GFD adherence in a prospective multicenter clinical trial including 64 children with celiac disease. Stool gluten peptides and blood tests (tTG and deamidated gliadin peptide, or DGP) were analyzed at diagnosis, and at 6, 12, and 24 months thereafter. Gluten consumption was estimated from the stool gluten peptide levels.

Most children (97%) had detectable gluten peptides at diagnosis, confirming the diagnosis and confirming that most of the children were eating gluten before their diagnosis. On a gluten‐free diet, 87% of the 64 children had no detectable GIP at 6 months, but this rate decreased to 75% at 24 months (i.e., 25% of children had recently consumed gluten when tested at 24 months).

As expected, mean estimated gluten exposure dropped from 5.5 grams of gluten per day at diagnosis to only 0.14 per day at 6 months. However, gluten exposure later increased to 0.6 g/day at 24 months. This seems counter‐intuitive, as one would expect the ability to follow a true GFD to improve with time, rather than worsen. This higher level of gluten exposure is likely explained by a relaxation of the diet over time. In contrast, DGP antibodies normalized, and only 1 in 5 subjects had elevated tTG by 24 months.

Gluten ingestion, whether accidental or intentional, was more common in the older children. In the under 2 years age group, only 6% (1 in 17) had gluten in their stool, likely because parents controlled their diet. In the 2‐6 years age group, 24% (1 in 4) had gluten in their stool. Lastly, in the 7‐18 years group, 35% (1 in 3) children had gluten in their stool.

Half of the children with positive GIP in stools on a GFD had more than one positive, suggesting a behavioral pattern involving repeated or chronic gluten exposure. Furthermore, some children had stool GIP levels similar to those of healthy children on a gluten-containing diet.

The tTG tests had low sensitivity to identify patients with stool gluten peptides, and dietitian assessment was only moderately correlated with gluten peptide detection. These results suggest that neither of these methods are good measures of GFD adherence.

In conclusion, serial analysis of stool GIP in a two-year period since diagnosis confirmed the expected substantial decrease in gluten consumption shortly after starting the GFD, yet also revealed that children with celiac disease might be relaxing their diets over time. Measuring GIP in stool is helpful for monitoring GFD adherence and is likely to replace the need for additional invasive tests for the follow‐up of celiac disease.

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  1. Ghazzawi Y, Rubio-Tapia A, Murray JA, Absah I. Mucosal healing in children with treated celiac disease. J Pediatr Gastroenterol Nutr. 2014; 59:229-231.
  2. Comino I, Fernández-Bañares F, Esteve M, et al. Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients. Am J Gastroenterol. 2016 Oct;111(10):1456-1465
  3. Silvester JA, Kurada S, Szwajcer A, Kelly CP, Leffler DA, Duerksen DR. Tests for serum transglutaminase and endomysial antibodies do not detect most patients with celiac disease and persistent villous atrophy on gluten‐free diets: a meta‐analysis. Gastroenterol2017; 153:689‐701.
  4. Koletzko S, Auricchio R, Dolinsek J, Gillet P, Korponay-Szabo I, Kurppa K, et al., No need for routine endoscopy in children with celiac disease on a gluten-free diet. J Pediatr Gastroenterol Nutr. 2017; 65:267-269.
  5. Moreno et al. Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing. Gut. 2017; Feb; 66(2):250-257.