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IBD metabonomics predicts phenotype, disease course, and treatment response.

ABSTRACT: Metabonomics in inflammatory bowel disease (IBD) characterizes the effector molecules of biological systems and thus aims to describe the molecular phenotype, generate insight into the pathology, and predict disease course and response to treatment. Nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), and integrated NMR and MS platforms coupled with multivariate analyses have been applied to create such metabolic profiles. Recent advances have identified quiescent ulcerative colitis as a distinct molecular phenotype and demonstrated metabonomics as a promising clinical tool for predicting relapse and response to treatment with biologics as well as fecal microbiome transplantation, thus facilitating much needed precision medicine. However, understanding this complex research field and how it translates into clinical settings is a challenge. This review aims to describe the current workflow, analytical strategies, and associated bioinformatics, and translate current IBD metabonomic knowledge into new potential clinically applicable treatment strategies, and outline future key translational perspectives.

SUBMITTER: Bjerrum JT

PROVIDER: S-EPMC8379620 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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IBD metabonomics predicts phenotype, disease course, and treatment response.

Bjerrum Jacob T JT Wang Yulan L YL Seidelin Jakob B JB Nielsen Ole H OH

EBioMedicine 20210819

Metabonomics in inflammatory bowel disease (IBD) characterizes the effector molecules of biological systems and thus aims to describe the molecular phenotype, generate insight into the pathology, and predict disease course and response to treatment. Nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), and integrated NMR and MS platforms coupled with multivariate analyses have been applied to create such metabolic profiles. Recent advances have identified quiescent ulcerative co ...[more]

PMID: 34419930

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Project description:IntroductionInflammatory bowel diseases (IBDs) are chronic diseases of unknown cause characterised by a progressive and unpredictable disease course. In the last decade, biological treatment has become a cornerstone in the treatment of IBD. However, one-in-three-to-four patients do not respond to first-line biological agents and another third of patients see their response diminish over time. This highlights an unmet need for optimising the use of biologicals and the prediction of treatment response. Considering the multifaceted nature of IBD, we hypothesise that multiomics profiling of sequential samples from single patients could facilitate the discovery of predictive biomarkers of response to biological therapy and disease course.MethodsThis is a multicentre prospective cohort study which will enrol 840 biological-naïve patients with IBD who initiate biological therapy in a 3-year period. Primary outcomes are the occurrence of primary non-response (evaluated at weeks 14-16) and loss of response (evaluated during entire follow-up in patients who obtain partial or full response after induction period). Each patient will be followed up for their clinical data for at least 1 year or till the end of study period (up to 4 years). Blood and stool samples will be collected sequentially during the first year of biological treatment. Intestinal tissue will be sampled after 1 year of treatment and whenever an endoscopy is performed. Samples will undergo transcriptomic, proteomic and microbial DNA analyses. Omics data will be integrated with clinical data to identify a panel of predictive biomarkers of response to biological therapy and disease behaviour in patients with IBD.Ethics and disseminationEthical approval has been obtained from the Danish Ethics Committee (H-18064178). Inclusion is ongoing at three study centres and will be initiated in two additional centres. Both positive and negative study results will be disseminated through peer-reviewed journals according to Strengthening the Reporting of Observational Studies in Epidemiology guidelines, as well as presented at international conferences.

Dataset Information

IBD metabonomics predicts phenotype, disease course, and treatment response.

Publications

IBD metabonomics predicts phenotype, disease course, and treatment response.

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