Molecular classification of IBD: diagnostic and therapeutic potential

Affecting almost 1% of the western population with an exponential escalation in westernizing countries, inflammatory bowel diseases (IBD) have evolved into a global disease at the turn of the twenty-first century. Crohn’s disease and ulcerative colitis, the opposite ends of the IBD spectrum, are characterized by chronic, idiopathic, progressive and relapsing inflammation of gastrointestinal tract. Owing to the complex interaction of the gut microbiome with the immune system in genetically predisposed individuals, patients with IBD have a heterogeneous clinical phenotype and outcome. Nonetheless, disease management is much less heterogeneous as broad-spectrum anti-inflammatory agents are the first line treatments inducing clinical and endoscopic remission in only 30-50% of the patients, thus leaving large margins for improvement. Nowadays, novel biological treatments, such as anti-IL-12/IL-23 and anti-integrin agents, as well as small molecules targeting Janus Kinases introduce new dilemmas of selecting the right therapy regimen for the right patient considering the interindividual differences in both response and adverse events. The chronic and incurable nature of IBD and its substantial morbidity, health- care expenses and loss of productivity in the work environment highlight the importance of targeted therapy. This, together with advances in scientific technologies, propose that comprehensive patient characterization could be extremely informative regarding the pathophysiological processes underlying the development of IBD and its clinical management. We therefore aim to characterize the different components driving disease in an individual patient by screening the patient's genome, transcriptome, proteome and microbiome and perform integration of all these ‘-omics’ layers. This will be the basis to construct an index, reflecting the proportional contribution of the different mechanisms in a given patient. Then we will explore the correlation of the index with meaningful clinical outcomes and its therapeutic value. The index will ideally lead to a highly optimized personal regime to manage IBD, maximizing treatment response while avoiding unwanted adverse effects.