Application of metabolomics to the study of irritable bowel syndrome

Abstract

Irritable bowel syndrome (IBS) is diagnosed based on symptoms 1 and is the most commonly diagnosed bowel disorder. 2 While this symptom-based approach has the advantage of limiting unnecessary testing 3 compared with a "diagnosis of exclusion" approach, the gastrointestinal tract has a limited symptom repertoire. Consequently, this symptom-based diagnosis captures a large but heterogeneous patient population, with multiple pathophysiological mechanisms underlying symptoms. 4 Using the Rome IV criteria, IBS subgroups are based on the predominant bowel habit, that is, IBS with constipation predominance (IBS-C), with diarrhea predominance (IBS-D), a mix between constipation and diarrhea (IBS-M) and unclassified (IBS-U). This method of classification of IBS is useful for clinical management; however, these subtypes may not reflect underlying pathophysiology. 5 While preclinical models have provided important insights, the complexity of IBS is notoriously difficult to model and mechanistic studies in humans are challenging due to their potentially invasive requirements. Therefore, new approaches are needed that might enable non-invasive studies with sufficient sensitivity and specificity to advance the field. In this issue of the journal, Lee et al focused on IBS-D patients and aimed to characterize fecal metabolite profiles of patients compared with healthy controls as well as to determine if diarrhea in and of itself can impact fecal metabolite composition. 6 This review will focus on the use of metabolomics to study IBS patients highlighting key methodological issues underlying the interpretation of these studies, whether identified molecules provide novel insights into Abstract The pathophysiology of irritable bowel syndrome and the detection of biomarkers of specific mechanisms and/or predictors of therapeutic response remain elusive. This roadblock reflects, in large part, the complexity and heterogeneity of the disorder. Recently, there has been growing evidence of a dietary and/or microbiome interaction with the host that may trigger symptoms in a subset of patients. While a number of techniques are available to examine these potential interactions, "omic" approaches such as metabolomics are becoming more widely used. Metabolomics measures hundreds and potentially thousands of known and unknown small molecule chemicals (metabolites) to provide a unique look into mechanisms that underlie symptom generation and potential predictors of therapeutic response. In this issue of the journal, Lee et al use nuclear magnetic resonance (NMR) to demonstrate the value of this approach to study IBS. This review examines the use of metabolomics to better understand IBS, focusing on what has been learned to date, practical and technical considerations, its potential for future research and how the study by Lee et al have contributed to these concepts. K E Y W O R D S irritable bowel syndrome, mass spectometry, metabolites, metabolomics, microbiota, nuclear magnetic resonance

Comorbidities, biomarkers and cause specific mortality in patients with irritable bowel syndrome: A phenome‐wide association study

“…Reliable biomarkers to distinguish IBS from other gastrointestinal inflammatory diseases or to evaluate the progression of the disease are subject of research but remain elusive and still warrant further validation. 56,57 Our findings indicate that the measurement of serum GlycA levels may play a potential role within IBS diagnosis or monitoring and might indicate whether IBS patients are at increased risk for a severe course of disease. We recommend further investigation of its relation to IBS, especially the relation to IBS-D, in other larger cohorts, as we can only detect an association through our study, but not a causal link.…”

Multi-omics profiles of the intestinal microbiome in irritable bowel syndrome and its bowel habit subtypes

“…Large studies of microbiome composition by 16S rRNA gene sequencing or shotgun metagenomics have in some cases shown minimal diversity change and taxonomic associations with IBS, while others have reported reduced diversity and taxonomic shifts that were not consistent across studies [6][7][8][9][10]. Recent studies have shifted to focus on functional characterization of the microbiome by shotgun metagenomics, which assesses functional potential by microbial gene content, or metabolomics, which assesses products of bacterial metabolism detected in feces [7,[11][12][13][14][15][16]. While these studies have reported significant shifts in gene content and metabolites, the specific features have not been consistent across studies.…”

Doing better with functional gastrointestinal disorders? Profiling gut microbiota and circulating antibodies to CdtB and vinculin

“…A recent review has pointed on the absence of a common metabolomic profile in IBS patients. 17 Liu Y et al 18 found no significant differences in community structures between IBS and healthy controls at the amplicon sequence variants level. However, IBS has been differentiated from healthy controls at genus level by using machine learning approaches, and authors detected nine new microbiome biomarkers of IBS.…”

“…The significant heterogeneity among studies depends on different methods, sampling modality and geographical settings. A recent review has pointed on the absence of a common metabolomic profile in IBS patients 17 …”