Differentiating coeliac disease from irritable bowel syndrome by urinary volatile organic compound analysis--a pilot study.

Ramesh P Arasaradnam,Ruth Harbord,Nicola O’Connell,Richard Savage,Karna D Bardhan,Michael J Mcfarlane,Samantha Chambers,James A Covington,Chuka U Nwokolo,Eric Westenbrink,Catherine Bailey,John Green

doi:10.1371/journal.pone.0107312

Abstract

Coeliac disease (CD), a T-cell-mediated gluten sensitive enteropathy, affects ∼1% of the UK population and can present with wide ranging clinical features, often being mistaken for Irritable Bowel Syndrome (IBS). Heightened clinical awareness and serological screening identifies those with potential coeliac disease; the diagnosis is confirmed with duodenal biopsies, and symptom improvement with a gluten-free diet. Limitations to diagnosis are false negative serology and reluctance to undergo biopsy. The gut microbiome is altered in several gastrointestinal disorders, causing altered gut fermentation patterns recognisable by volatile organic compounds (VOC) analysis in urine, breath and faeces. We aimed to determine if CD alters the urinary VOC pattern, distinguishing it from IBS. 47 patients were recruited, 27 with established CD, on gluten free diets, and 20 with diarrhoea-predominant IBS (D-IBS). Collected urine was stored frozen in 10 ml aliquots. For assay, the specimens were heated to 40±0.1°C and the headspace analysed by Field Asymmetric Ion Mobility Spectrometry (FAIMS). Machine learning algorithms were used for statistical evaluation. Samples were also analysed using Gas chromatography and mass spectroscopy (GC-MS). Sparse logistic regression showed that FAIMS distinguishes VOCs in CD vs D-IBS with ROC curve AUC of 0.91 (0.83–0.99), sensitivity and specificity of 85% respectively. GCMS showed a unique peak at 4′67 found only in CD, not D-IBS, which correlated with the compound 1,3,5,7 cyclooctatetraene. This study suggests that FAIMS offers a novel, non-invasive approach to identify those with possible CD, and distinguishes from D-IBS. It offers the potential for monitoring compliance with a gluten-free diet at home. The presence of cyclooctatetraene in CD specimens will need further validation.

Highlights

Coeliac disease is a T-cell mediated gluten sensitive enteropathy, affecting approximately 1% of the UK population, only 10–15% of patients with the condition are diagnosed [1,2]
Some patients were established on long term (10 years or more) gluten free diets and some were more recent diagnoses. tTG serology was performed on all the patients, either at initial screening or for monitoring in the long term patients. 20 patients had D-Irritable Bowel Syndrome (IBS) according to the ROME II criteria with negative tTG serology, normal TSH as well as colonoscopy
We identified over 70 separate chemicals, but there was a high variation in individual sample composition, but a number of volatile organic compounds (VOC) were found to be present in urine samples with a significant degree of certainty

Summary

Introduction

Coeliac disease is a T-cell mediated gluten sensitive enteropathy, affecting approximately 1% of the UK population, only 10–15% of patients with the condition are diagnosed [1,2]. Anti endomysial tests showed a lower sensitivity than for dual (IgA and IgG) anti TTG antibodies (62–68% vs 90–92%) but a higher specificity (80–99% vs 81– 83%). Combination testing of both endomysial and TTG antibodies has shown a slight increase in positive predictive value, negative predictive value and specificity, at the expense of sensitivity [6]

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