Fecal gluten peptides reveal limitations of serological tests and food questionnaires for monitoring gluten-free diet in coeliac disease patients
Comino I, Fernandez-Banares F, Esteve M et al
American Journal of Gastroenterology 2016; 111:1456-65; doi:10.1038/ajg.2016.439; Published online 20/09/16
Avoiding dietary gluten can be challenging and may considerably affect quality of life. Estimated compliance rates vary considerably and can depend on a number of different factors. Small bowel biopsy for the assessment of mucosal inflammation is considered the ‘gold standard’ for the diagnosis of coeliac disease (CD), and may therefore be considered the ideal parameter for monitoring gluten-free diet (GFD) compliance.
American Journal of Gastroenterology 2016; 111:1456-65; doi:10.1038/ajg.2016.439; Published online 20/09/16
Avoiding dietary gluten can be challenging and may considerably affect quality of life. Estimated compliance rates vary considerably and can depend on a number of different factors. Small bowel biopsy for the assessment of mucosal inflammation is considered the ‘gold standard’ for the diagnosis of coeliac disease (CD), and may therefore be considered the ideal parameter for monitoring gluten-free diet (GFD) compliance.
However, the invasiveness and cost of this approach makes it impractical for use in this regard. Unfortunately, other, more commonly employed methods for assessing dietary compliance demonstrate a poor degree of accuracy. Individuals tend to over-report their level of adherence in self-reported interviews/ questionnaires, and follow-up serology has been shown to have a poor correlation with mucosal healing and may therefore underestimate the activity of CD. The purpose of this prospective, nonrandomised, partially blinded, multicentre study was to confirm the clinical usefulness of measuring faecal gluten immunogenic peptides (GIP) as a marker of adherence to a GFD.
A total of 272 subjects (153 females and 119 males, aged 0-72 years) were included in the study, recruited between April 2012 and June 2014 at 13 Spanish hospitals. Of these, 188 subjects were GFD-treated coeliac patients and 84 were healthy controls (73 positive controls – healthy children and adults on an unrestricted gluten-containing diet; 11 negative controls – healthy infants 0-8 months of age who had not yet been introduced to gluten). Subjects were given a detailed, structured food intake questionnaire to complete at home over a 4 day period, after which they were also asked to collect 2-4g of stool sample. Subjects were then invited to attend a follow-up visit during which blood samples were obtained and information related to diagnosis, duration of CD and clinical outcome were also collected for the coeliac group.
Of the 188 coeliac patients, 56 (29.8%) had detectable levels of GIP in stools (as would be expected, all positive controls, except 1, had GIP in stools, none of negative controls had evidence of GIP in stools). A positive significant association between age and GIP content in stools revealed increasing dietary transgressions with advancing age (p=0.025). This is likely to be reflective of increasing autonomy to direct own food choices over time. Among adolescent and adult subjects >13 years, 39.2% had GIP-positive stool samples. Adherence to the GFD was also found to be closely related to gender in certain age groups, in the >13 year group, 60% of men v’s 31.5% of women had GIP-positive stool samples. Furthermore, a non-significant tendency for greater non-compliance amongst patients who had been following a GFD for the longest was also observed.
No association was found between faecal GIP and dietary questionnaire or anti-tTG antibody results. Non-compliance was detected in approx only 18% of patients when assessing adherence by either dietary questionnaire or by determination of anti-tTG serum antibodies alone. Interestingly, 70% of patients who had GIP-positive stool samples did not declare any gluten consumption in their food questionnaires. Patients with a strong positive value for GIP in stools were 2-4 times more likely to have positive anti-tTG and anti-DGP IgA antibodies, respectively, compared to patients with undetectable levels of GIP. However, for those with less strongly positive stool-GIP levels (<30µg/g faeces), 65% had negative anti-tTG IgA and 83% had negative anti-DGP IgA, thus confirming the low sensitivity of serology for monitoring response to diet.
In conclusion, this study demonstrated a level of dietary compliance amongst coeliac patients on an established GFD that is lower than that shown using traditional dietary questionnaire or serological methods. Almost one third of patients on an established GFD were non-compliant with diet, with this figure being substantially higher amongst older patients and those of male gender. The inability to directly measure GFD adherence is an unsolved problem for both clinicians and researchers, for which the analysis of GIP in stools provides a possible solution and route to improving diagnosis and clinical management of CD, particularly for nonresponsive and refractory patients.
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A total of 272 subjects (153 females and 119 males, aged 0-72 years) were included in the study, recruited between April 2012 and June 2014 at 13 Spanish hospitals. Of these, 188 subjects were GFD-treated coeliac patients and 84 were healthy controls (73 positive controls – healthy children and adults on an unrestricted gluten-containing diet; 11 negative controls – healthy infants 0-8 months of age who had not yet been introduced to gluten). Subjects were given a detailed, structured food intake questionnaire to complete at home over a 4 day period, after which they were also asked to collect 2-4g of stool sample. Subjects were then invited to attend a follow-up visit during which blood samples were obtained and information related to diagnosis, duration of CD and clinical outcome were also collected for the coeliac group.
Of the 188 coeliac patients, 56 (29.8%) had detectable levels of GIP in stools (as would be expected, all positive controls, except 1, had GIP in stools, none of negative controls had evidence of GIP in stools). A positive significant association between age and GIP content in stools revealed increasing dietary transgressions with advancing age (p=0.025). This is likely to be reflective of increasing autonomy to direct own food choices over time. Among adolescent and adult subjects >13 years, 39.2% had GIP-positive stool samples. Adherence to the GFD was also found to be closely related to gender in certain age groups, in the >13 year group, 60% of men v’s 31.5% of women had GIP-positive stool samples. Furthermore, a non-significant tendency for greater non-compliance amongst patients who had been following a GFD for the longest was also observed.
No association was found between faecal GIP and dietary questionnaire or anti-tTG antibody results. Non-compliance was detected in approx only 18% of patients when assessing adherence by either dietary questionnaire or by determination of anti-tTG serum antibodies alone. Interestingly, 70% of patients who had GIP-positive stool samples did not declare any gluten consumption in their food questionnaires. Patients with a strong positive value for GIP in stools were 2-4 times more likely to have positive anti-tTG and anti-DGP IgA antibodies, respectively, compared to patients with undetectable levels of GIP. However, for those with less strongly positive stool-GIP levels (<30µg/g faeces), 65% had negative anti-tTG IgA and 83% had negative anti-DGP IgA, thus confirming the low sensitivity of serology for monitoring response to diet.
In conclusion, this study demonstrated a level of dietary compliance amongst coeliac patients on an established GFD that is lower than that shown using traditional dietary questionnaire or serological methods. Almost one third of patients on an established GFD were non-compliant with diet, with this figure being substantially higher amongst older patients and those of male gender. The inability to directly measure GFD adherence is an unsolved problem for both clinicians and researchers, for which the analysis of GIP in stools provides a possible solution and route to improving diagnosis and clinical management of CD, particularly for nonresponsive and refractory patients.
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