Abstract
Biological markers that measure gut health and diagnose functional gastro-intestinal (GI) disorders, such as irritable bowel syndrome (IBS), are lacking. The objective was to identify and validate a biomarker panel associated with the pathophysiology of IBS that discriminates IBS from healthy controls (HC), and correlates with GI symptom severity. In a case-control design, various plasma and fecal markers were measured in a cohort of 196 clinical IBS patients and 160 HC without GI symptoms. A combination of biomarkers, which best discriminates between IBS and HC was identified and validated in an independent internal validation set and by permutation testing. The correlation between the biomarker panel and GI symptom severity was tested in IBS patients and in a general population cohort of 958 subjects. A set of 8 biomarker panel was identified to discriminate IBS from HC with high sensitivity (88.1%) and specificity (86.5%). The results for the IBS subtypes were comparable. Moreover, a moderate correlation was found between the biomarker panel and GI symptom scores in the IBS (r = 0.59, p < 0.001) and the general population cohorts (r = 0.51, p = 0.003). A novel multi-domain biomarker panel has been identified and validated, which correlated moderately to GI symptom severity in IBS and general population subjects.
Highlights
Treatment efficacy of functional GI disorders, such as Irritable Bowel Syndrome (IBS), are lacking
All GI symptom scores were higher in IBS patients compared to healthy controls (HC)
Chromogranin A (CgA) and calprotectin were significantly increased, while HBD2, and the SCFAs, valerate and caproate, were significantly decreased in IBS patients compared to HC
Summary
Treatment efficacy of functional GI disorders, such as Irritable Bowel Syndrome (IBS), are lacking. Strong evidence exists for a combination of rather subtle pathophysiological changes, such as low-grade mucosal and systemic immune activation, intestinal barrier dysfunction, dysregulation in neural and neuro-hormonal signaling and altered microbiota and host-microbe interaction, that contribute to symptom generation in IBS12 These mechanisms do overlap with the domains of gut health as described by Bischoff[1]. We hypothesized that biomarkers related to several domains of gut health and associated with the pathophysiology of IBS, can be combined and used as a highly sensitive and specific biomarker panel to discriminate clinically diagnosed IBS patients form healthy controls. The primary objective of the present study was to assess levels of selected plasma and fecal biomarkers, related to several domains of gut health, and to identify and validate a non-invasive biomarker panel, which best discriminates IBS patients from healthy controls. The secondary objective was to correlate the biomarker panel to GI symptom severity in clinical IBS patients as well as in a large general population cohort
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