Multi-Omics Characterization of Colon Mucosa and Submucosa/Wall from Crohn's Disease Patients

Crohn's disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by transmural disease. The concept of transmural healing (TH) has been proposed as an indicator of deep clinical remission of CD and as a predictor of favorable treatment endpoints. Understanding the pathophysiology involved in transmural disease is critical to achieving these endpoints. However, most studies have focused on the intestinal mucosa, overlooking the contribution of the intestinal wall in Crohn's disease. Multi-omics approaches have provided new avenues for exploring the pathogenesis of Crohn's disease and identifying potential biomarkers. . We aimed to use transcriptomic and proteomic technologies to compare immune and mesenchymal cell profiles and pathways in the mucosal and submucosa/wall compartments to better understand chronic refractory disease elements to achieve transmural healing. The results revealed similarities and differences in gene and protein expression profiles, metabolic mechanisms, and immune and non-immune pathways between these two compartments. Additionally, the identification of protein isoforms highlights the complex molecular mechanisms underlying this disease, such as decreased RTN4 isoforms (RTN4B2 and RTN4C) in the submucosa/wall which may be related to the dysregulation of enteric neural processes. These findings have the potential to inform the development of novel therapeutic strategies to achieve TH Overall design: Human colon resection tissues were collected at surgery and dissected into regional compartments of mucosa and submucosa/wall for this study . Ulceration of some mucosal samples prevented their inclusion in this study, and sever-al samples were excluded from analysis due to poor sample or data quality. Mucosa samples (N = 25) consist 8 CD inflamed, 9 CD non-inflamed, and 8 normal (non-IBD control patients (cancerwith cancer or diverticular disease), and submucosa/wall samples (N = 27) consist 10 CD inflamed, 8 CD non-inflamed, and 9 normal (non-IBD control patients (cancerwith cancer or diverticular disease)