Application of a Novel Tool for Diagnosing Bile Acid Diarrhoea

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.

High Prevalence of Idiopathic Bile Acid Diarrhea Among Patients With Diarrhea-Predominant Irritable Bowel Syndrome Based on Rome III Criteria

“…17 However, in the current climate, as none of these tests are routinely available in countries such as the USA, there is interest in the development of a simple, cheap, and readily available biomarker that will help screen for patients that potentially have BAD who can then subsequently be referred on for confirmatory tests. Of these, measurement of serum FGF-19, 18 identification of the primary bile acids cholate and chenodeoxycholate in a single stool sample, 19,20 or detection of volatile organic compounds in a single urine sample (presumed to be a consequence of dysbiosis secondary to elevated levels of colonic bile acids), 21 have all shown initial promising results, but require further work to validate their clinical applicability.…”

Non-Invasive Distinction of Non-Alcoholic Fatty Liver Disease using Urinary Volatile Organic Compound Analysis: Early Results

“…The Random Forest algorithm (implemented in the R package 'randomForest' , version 4.6-10, R version 3.1.1) (http://cran.ro-project.org/web/ packages/randomForest/index.html) was applied inside the cross-validation loop. From previous studies we have shown that Random Forest provides the best performance for these types of datasets and this was applied here [20][21][22][23][24]. …”

“…Patients with significant pelvic radiotherapy induced gastrointestinal side effects have also been identified in this manner [22]. More recent developments include the detection of bile acid diarrhoea (BAD) and distinction of coeliac disease from irritable bowel syndrome by urinary VOC analysis [23,24]. Thus, gas phase biomarkers have been of significant interest as a method of positively diagnosing patients with a wide range of diseases relevant to the field of gastroenterology [25].…”

“…This would indicate that they represent the complex interaction of colonocytes, human gut microflora and invading pathogens [26]. The resultant products of fermentation, 'the fermentome' can exist in the gaseous phase and are present in exhaled air, sweat, urine and faeces [23,25,[27][28][29]. Their presence in bodily secretions from sites other than the gastrointestinal tract (sweat, exhaled air and urine) is presumed possible due to the altered gut permeability afforded in certain disease states [27].…”

Low Cost Optical Electronic Nose for Biomedical Applications

“…This interest arises from the eNoses ability to be non-invasive, point of care, can be produced at price point appropriate for the medical profession and can give a real-time answer. Our research group have previous reported on the efficacy of this approach in detecting and monitoring a variety of gastroenterological and metabolic disorders [3,4].…”