Integrating gut microbiome and host transcriptomics for the personalized management of IBD.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), affects an estimated 6.8 million individuals worldwide. Although biological or small molecule drug therapies can improve patient outcomes, loss of response to treatment over time remains high, highlighting the need for new precision medicine strategies. Dysbiosis of the gut microbiome is characterized by the loss of beneficial microbes and an overgrowth of pro-inflammatory pathobionts. In IBD, gut dysbiosis contributes to chronic intestinal inflammation via altered metabolite profiles and epithelial barrier disruption. Recent advancements in multi-omics integration offer approaches to better understand the pathogenesis of IBD. Epigenomic studies have revealed disease-specific DNA methylation and enhancer activation patterns that reshape immune pathways and compromise epithelial barrier integrity, key mechanisms in IBD pathophysiology. These molecular signatures allow for the stratification of IBD patients into distinct subgroups, allowing for more targeted therapeutic strategies. Here we explore the potential benefits of integrating gut microbiome and both host transcriptomics and epigenomics to improve disease management in IBD patients. While challenges remain - such as data standardization, computational complexity, and cost - the progression of multi-omics methodologies is expected to improve patient outcomes by reducing high treatment failure rates in IBD patients.