Application of a Novel Tool for Diagnosing Bile Acid Diarrhoea

James Covington,Nicola O'Connell,James Cullis,Catherine Bailey,Ruth Harbord,Nigel Williams,Chuka Nwokolo,Karna Bardhan,Ramesh Arasaradnam,Eric Westenbrink,Nathalie Ouaret

doi:10.3390/s130911899

Abstract

Bile acid diarrhoea (BAD) is a common disease that requires expensive imaging to diagnose. We have tested the efficacy of a new method to identify BAD, based on the detection of differences in volatile organic compounds (VOC) in urine headspace of BAD vs. ulcerative colitis and healthy controls. A total of 110 patients were recruited; 23 with BAD, 42 with ulcerative colitis (UC) and 45 controls. Patients with BAD also received standard imaging (Se75HCAT) for confirmation. Urine samples were collected and the headspace analysed using an AlphaMOS Fox 4000 electronic nose in combination with an Owlstone Lonestar Field Asymmetric Ion Mobility Spectrometer (FAIMS). A subset was also tested by gas chromatography, mass spectrometry (GCMS). Linear Discriminant Analysis (LDA) was used to explore both the electronic nose and FAIMS data. LDA showed statistical differences between the groups, with reclassification success rates (using an n-1 approach) at typically 83%. GCMS experiments confirmed these results and showed that patients with BAD had two chemical compounds, 2-propanol and acetamide, that were either not present or were in much reduced quantities in the ulcerative colitis and control samples. We believe that this work may lead to a new tool to diagnose BAD, which is cheaper, quicker and easier that current methods.

Highlights

Chronic diarrhoea is a significant clinical problem estimated to affect up to 5% of the population [1].There are many causes for chronic diarrhea, but bile acid diarrhoea (BAD) is one of the commonest [2].Bile acids are essential for the emulsification and subsequent digestion of fat
The capability of the methods for discriminating between urine samples from patients with the less common form of diarrhoea associated with inflammation and the more common form due to bile acid diarrhoea
This distinction is important to make for two reasons: (1) the clinical management is very different for both these conditions and (2) therapeutic efficacy that is offered is effective especially as newer therapies are becoming available suggesting a greater number of people are likely to gain benefit if the condition can be diagnosed

Summary

Introduction

Chronic diarrhoea is a significant clinical problem estimated to affect up to 5% of the population [1].There are many causes for chronic diarrhea, but bile acid diarrhoea (BAD) is one of the commonest [2].Bile acids are essential for the emulsification and subsequent digestion of fat. There are many causes for chronic diarrhea, but bile acid diarrhoea (BAD) is one of the commonest [2]. More than 98% of bile acids produced are reabsorbed back in to circulation, with less than 2% lost in faeces [3]. The SeHCAT retention test involves a synthetically tagged isotope, which is swallowed and diluted within the bile acid circulation and able to track its movements. This is the accepted gold standard to diagnose BAD, but the cost is prohibitive—approximately £210 ($320) per patient and in some areas patients have been denied the opportunity to have this diagnosis made

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