Metabolomics in the Clinical Diagnosis of Inflammatory Bowel Disease

Abstract

Background: Crohn's disease and ulcerative colitis represent the 2 major phenotypes of inflammatory bowel disease (IBD) that are characterized by chronic inflammation of all or parts of the gastrointestinal tract. The pathogenesis of both diseases is influenced by genetic predispositions as well as microbial and environmental factors. Currently, there is an emerging consensus hypothesis that a microbial dysbiosis is involved in initiating the disease or in maintaining it. These compositional alterations may be reflected in altered metabolic activities of the gut microbiota and has led to the use of ‘omic' profiling to improve the understanding of the pathophysiology of IBD. Key Messages: In the past few years, a metabolic approach has increasingly been applied in a number of studies of experimental and human IBD which were mostly focused on exploring disease-related metabolites to gain more insight into metabolic pathways. Metabolomics involves the high throughput identification, characterization and quantification of small molecule metabolites by different analytical techniques and has been performed in different biofluids such as serum/plasma, urine or fecal samples. The application of such a metabolite profiling technique has revealed different metabolites that allow the discrimination of IBD patients from healthy controls. In addition, separate IBD subtypes could be differentiated. Some of these metabolic changes were directly associated to alterations of specific gut microbial populations, implying a perturbation in the gut microbiome in the development of IBD. Conclusions: This review covers the emerging contribution of metabolomics for the discovery of an IBD signature and to identify biomarkers linked with a metabolic imbalance. For the implementation of metabolomics as a diagnostic tool in IBD, large prospective cohort studies are necessary.

Dietary Protein and Amino Acid Supplementation in Inflammatory Bowel Disease Course: What Impact on the Colonic Mucosa?

“…Moreover, the host-microbiota ‘co-metabolite’ p -cresol sulfate, which is produced from the L-tyrosine derived bacterial metabolite p -cresol, was decreased in the urine of CD patients [56]. In accordance with this latter result, another study found decreased p -cresol levels in the feces of IBD patients [52]. In this study, the authors found a decreased level of the indolic compounds, which are produced from tryptophan by intestinal bacteria, in accordance with previous results [57].…”

“…Untargeted metabolomics revealed that there is an IBD-associated metabolome in feces [52], and some of this metabolic signature is related to bacterial metabolites derived from AA. Interestingly, while several studies found an increase in AA fecal concentrations in IBD patients [53,54], other studies showed a complex remodeling of AA-catabolism by the microbiota, with some AA-derived bacterial compounds being increased while others decreased.…”

“…Metabolomic studies revealed an alteration of AA metabolism in the serum and urine of IBD patients [52]. Indeed, the analysis of the plasma aminogram has been shown to be an effective tool to diagnose and monitor disease activity, notably according to histidine and tryptophan concentrations that are negatively correlated with C-reactive protein in UC and CD patients [96].…”

Noninvasive Metabolic Profiling for Painless Diagnosis of Human Diseases and Disorders

“…Crohn's disease along with ulcerative colitis makes up the majority of inflammatory bowel diseases (IBD). In the last few years, urinary metabolic profiling studies have been extensively utilized for gaining more insight into metabolic pathways perturbed in IBD which in turn has provided a potential diagnostic and patient stratification tool for IBD [43]. A preliminary study involving urinary metabolic profiling exhibited potential in the diagnosis of hepatitis C virus infection in patients [44].…”

“…For the implementation of metabolic profiling as a nonnvasive diagnostic tool in clinical practices large scale prospective clinical studies are required in distant future. The main thrust areas involve diseases such as IBD [43], hepatitis C virus infection [44], depression associated with hepatitis B virus-infected patients [45], neurodegenerative disorders [66], ARDS [76], pleural mesothelioma [95], respiratory tract infections [97], nonalcoholic fatty liver disease [110,111] and rheumatic diseases [49]. …”