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

Arasaradnam RP, Westenbrink E, McFarlane MJ, Harbord R, Chambers S, O'Connell N, Bailey C, Nwokolo CU, Bardhan KD, Savage R, Covington JA - PLoS ONE (2014)

Bottom Line: 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.The presence of cyclooctatetraene in CD specimens will need further validation.

View Article: PubMed Central - PubMed

Affiliation: Clinical Sciences Research Institute, University of Warwick, Coventry, Warwickshire, United Kingdom; Department of Gastroenterology, University Hospital Coventry & Warwickshire, Coventry, Warwickshire, United Kingdom.

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.

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Related in: MedlinePlus

Raw FAIMS output for a Coeliac patient urine sample.
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pone-0107312-g001: Raw FAIMS output for a Coeliac patient urine sample.

Mentions: The analysis of the FAIMS data for coeliac patients and controls was carried out using three different machine learning classifiers, as described above. Figure 1 shows a raw plot of the data created by FAIMS technique. As mobility of a chemical is not constant and is a function of applied electric field, the instrument scans through a range of different settings (which is described by the dispersion field in figure 1), with the compensation voltage being a fixed DC voltage that compensates for the mobility of the molecule, allowing gas/vapour molecules with only that specific mobility to be measured.


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

Arasaradnam RP, Westenbrink E, McFarlane MJ, Harbord R, Chambers S, O'Connell N, Bailey C, Nwokolo CU, Bardhan KD, Savage R, Covington JA - PLoS ONE (2014)

Raw FAIMS output for a Coeliac patient urine sample.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199520&req=5

pone-0107312-g001: Raw FAIMS output for a Coeliac patient urine sample.
Mentions: The analysis of the FAIMS data for coeliac patients and controls was carried out using three different machine learning classifiers, as described above. Figure 1 shows a raw plot of the data created by FAIMS technique. As mobility of a chemical is not constant and is a function of applied electric field, the instrument scans through a range of different settings (which is described by the dispersion field in figure 1), with the compensation voltage being a fixed DC voltage that compensates for the mobility of the molecule, allowing gas/vapour molecules with only that specific mobility to be measured.

Bottom Line: 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.The presence of cyclooctatetraene in CD specimens will need further validation.

View Article: PubMed Central - PubMed

Affiliation: Clinical Sciences Research Institute, University of Warwick, Coventry, Warwickshire, United Kingdom; Department of Gastroenterology, University Hospital Coventry & Warwickshire, Coventry, Warwickshire, United Kingdom.

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.

Show MeSH
Related in: MedlinePlus