Single-cell omics in inflammatory bowel disease: recent insights and future clinical applications

Inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn’s disease (CD), are chronic conditions characterised by inflammation of the intestinal tract. Alterations in virtually all intestinal cell types, including immune, epithelial and stromal cells, have been described in these diseases. The study of IBD has historically relied on bulk transcriptomics, but this method averages signals across diverse cell types, limiting insights. Single-cell omic technologies overcome the intrinsic limitations of bulk analysis and reveal the complexity of multicellular tissues at a cell-by-cell resolution. Within healthy and inflamed intestinal tissues, single-cell omics, particularly single-cell RNA sequencing, have contributed to uncovering novel cell types and cell functions linked to disease activity or the development of complications. Collectively, these results help identify therapeutic targets in difficult-to-treat complications such as fibrostenosis, creeping fat accumulation, perianal fistulae or inflammation of the pouch. More recently, single-cell omics have gradually been adopted in studies to understand therapeutic responses, identify mechanisms of drug failure and potentially develop predictors with clinical utility. Although these are early days, such studies lay the groundwork for the implementation in clinical practice of new technologies in diagnostics, monitoring and prediction of disease prognosis. With this review, we aim to provide a comprehensive survey of the studies that have applied single-cell omics to the study of UC or CD, and offer our perspective on the main findings these studies contribute. Finally, we discuss the limitations and potential benefits that the integration of single-cell omics into clinical practice and drug development could offer.