Comparison of the metabolomic profiles of irritable bowel syndrome patients with ulcerative colitis patients and healthy controls: new insights into pathophysiology and potential biomarkers

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.