Faecal Scent as a Novel Non-Invasive Biomarker to Discriminate between Coeliac Disease and Refractory Coeliac Disease: A Proof of Principle Study.

Chris J Mulder,Nanne K.H De Boer,Maxine D Rouvroye,Gerd Bouma,Sofie Bosch,James A Covington,Tim G.J De Meij,Hanneke Beaumont,Edo Savelkoul,Alfian Wicaksono

doi:10.3390/bios9020069

Abstract

Currently, the gold standard for diagnosis of coeliac disease (CD) is based on serology and gastroduodenoscopy with histology of duodenal mucosal biopsies. The aim of this study was to evaluate the potential of faecal volatile organic compounds (VOCs) analysis as a novel, non-invasive tool to discriminate between CD in remission in patients on a gluten-free diet (GFD), refractory coeliac disease (RCD) and controls without CD. Patients with an established diagnosis of CD on a GFD, RCD and healthy controls (HC) were instructed to collect a faecal sample. All subjects completed questionnaires on clinical symptoms, lifestyle and dietary information. Faecal VOCs were measured using gas chromatography-ion mobility spectrometry. A total of 13 CD, 7 RCD and 10 HC were included. A significant difference in VOC profiles between CD and RCD patients (area under the curve (AUC) ± 95% CI: 0.91 (0.79–1) p = 0.000) and between CD and HC (AUC ± 95% CI: 0.71 (0.51–0.91) p = 0.0254) was observed. We found no significant differences between faecal VOC patterns of HC and RCD. Based on faecal VOCs, CD could be discriminated from RCD and HC. This implies that faecal VOC analysis may hold potential as a novel non-invasive biomarker for RCD. Future studies should encompass a larger cohort to further investigate and validate this prior to application in clinical practice.

Highlights

Coeliac disease (CD) is a chronic, immune-mediated enteropathy triggered by the ingestion of gluten in genetically predisposed individuals, with an estimated prevalence of 1% in Europe [1,2,3]
A distinction is made based on histology; whereas refractory coeliac disease (RCD) I has a benign population of intraepithelial lymphocytes (IEL) and generally improves after additional treatment, RCD II is characterized by abnormal or clonal IELs and has a poor prognosis with an increased risk for the development of enteropathy associated T cell lymphoma (EATL) [12]
Key symptoms leading to gastroduodenoscopy in the healthy controls (HC) group were: retrosternal pain (30%), globus (30%), idiopathic iron deficiency anaemia (20%), reflux (10%) or change in bowel habits (10%)

Summary

Introduction

37% of all diagnosed CD patients portray classical symptoms such as diarrhoea, weight loss and abdominal pain. Despite abstaining from gluten, a small minority (0.83 per 10,000 CD patients per year in The Netherlands) develops refractory coeliac disease (RCD) with persistent or recurrent villous atrophy [10]. This is often accompanied by severe diarrhoea, weight loss and malabsorption [11]. A distinction is made based on histology; whereas RCD I has a benign population of IELs and generally improves after additional treatment, RCD II is characterized by abnormal or clonal IELs and has a poor prognosis with an increased risk for the development of enteropathy associated T cell lymphoma (EATL) [12]

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