Comparison of the Metabolomic Profiles of Irritable Bowel Syndrome Patients With Ulcerative Colitis Patients and Healthy Controls

New Insights Into Pathophysiology and Potential Biomarkers

Ammar Hassanzadeh Keshteli; Karen L. Madsen; Rupasri Mandal; Guy E. Boeckxstaens; Premysl Bercik; Giada De Palma; David E. Reed; David Wishart; Stephen Vanner; Levinus A. Dieleman

Disclosures

Aliment Pharmacol Ther. 2019;49(6):723-732. 

In This Article

Abstract and Introduction

Abstract

Background: Evaluation of the metabolomic profile of patients with irritable bowel syndrome offers an opportunity to identify novel pathophysiological targets and biomarkers that could discriminate this disorder from related conditions.

Aim: To identify potential urinary biomarkers that discriminate irritable bowel syndrome patients from ulcerative colitis patients in remission and healthy controls and to explore the pathophysiology of irritable bowel syndrome using a metabolomic approach.

Methods: Urine samples were collected from 39 irritable bowel syndrome patients, 53 ulcerative colitis patients in clinical remission and 21 healthy controls. Urinary metabolites were identified and quantified using direct infusion/liquid chromatography tandem mass spectrometry and gas-chromatography mass spectrometry.

Results: Patients with irritable bowel syndrome had a unique urinary metabolome that could separate them from ulcerative colitis patients with an area under the curve = 0.99 (95% confidence interval 0.95-1.00). The most important metabolites for this separation were a group of amino acids and organic acids. In addition, subjects with irritable bowel syndrome could be discriminated from healthy controls using their metabolic fingerprints. Irritable bowel syndrome patients had lower urinary Phosphatidyl choline acyl-alkyl C38:6, dopamine and p-hydroxybenzoic acid than healthy controls. Levels of some urinary metabolites including histamine correlated significantly with irritable bowel syndrome symptom severity scores.

Conclusions: Irritable bowel syndrome patients have a unique urinary metabolomic profile compared to ulcerative colitis patients in clinical remission or healthy subjects. These data suggest that metabolomic profiling may provide important insights into pathophysiology and testable biomarkers to discriminate irritable bowel syndrome from other disorders that can mimic this condition and can be used to assess its severity and identify potential novel pathophysiological pathways.

Introduction

Irritable bowel syndrome (IBS) is the most commonly diagnosed gastrointestinal condition. It is a chronic functional gastrointestinal disorder (FGID) characterised by recurring abdominal pain, bloating, loose or frequent stools and/or constipation in the absence of structural or major inflammatory and biochemical abnormalities.[1] IBS is associated with impaired health-related quality of life and increased healthcare expenditures.[2] Globally, the pooled prevalence of IBS is 11%.[3] The complex and multifactorial pathophysiology of IBS includes genetic predisposition and visceral hypersensitivity along with abnormalities in gut motility, secretion, immune activity, autonomic nervous system function, permeability and microbial composition and function.[4]

Currently there is no biological marker or a distinct observable intestinal pathophysiology that is specific for IBS; thus diagnosis remains challenging.[5] At the present time, diagnosis of IBS is based on Rome IV criteria, which are symptom-based.[6] However, these criteria have been criticised for being complex and performing modestly in differentiating organic diseases from FGIDs.[7] Many IBS patients undergo unnecessary endoscopic evaluations to rule out organic conditions such as IBD due to overlapping symptoms.[8] Therefore, identification of biomarkers to discriminate IBS patients from healthy individuals and organic diseases is highly desirable.

Metabolomics, defined as the study of all metabolites in biological samples comprehensively has the potential to identify biomarkers for diagnosis or prognosis of diseases as well as helping to elucidate the pathophysiology of diseases.[9] Recently, a limited number of studies have used a metabolomic approach to identify metabolites in breath[10] or faecal[5,11] samples to discriminate between IBS patients and healthy volunteers or IBD patients. However, there is a need to perform further metabolomic studies in IBS settings[12] to validate previous findings and to identify metabolites in other easily accessible biological samples such as urine.

The primary aim of this study was to identify urinary metabolite profiles that could be used to differentiate IBS patients from healthy controls and IBD patients and secondarily, to determine if specific urinary biomarkers could distinguish IBS subtypes. We also aimed to investigate if metabolomics could provide new insight into the complex pathophysiology of IBS.

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