Clinical Value of Multiomics-Based Biomarker Signatures in Inflammatory Bowel Diseases: Challenges and Opportunities

Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), are complex and heterogeneous diseases characterized by a multifactorial etiology, therefore demanding a multimodal approach to disentangle the main pathophysiological components driving disease onset and progression. Adoption of a systems biology approach is increasingly advocated with the advent of multi-omics profiling technologies, aiming to improve disease classification, to identify disease biomarkers and to accelerate drug discovery for patients with IBD. However, clinical translation of multi-omics-derived biomarker signatures is lagging behind, since there are several obstacles that need to be addressed in order to realize clinically useful signatures. Multi-omics integration and IBD-specific identification of molecular networks, standardization and clearly defined outcomes, strategies to tackle cohort heterogeneity, and external validation of multi-omics-based signatures are critical aspects. While striving for personalized medicine in IBD, careful consideration of these aspects is however needed to adequately match biomarker targets (e.g. the gut microbiome, immunity or oxidative stress) with their corresponding utilities (e.g. early disease detection, endoscopic and clinical outcome). Theory-driven disease classifications and predictions are still governing clinical practice, while this could be improved by adopting an unbiased, data-driven approach relying on molecular data structures integrated with patient and disease characteristics. In the foreseeable future, the main challenge will lie in the complexity and impracticality of implementing multi-omics-based signatures into clinical practice. Still, this could be achieved by developing easy-to-use, robust and cost-effective tools incorporating omics-derived predictive signatures and through the design and execution of prospective, longitudinal, biomarker-stratified clinical trials.