P178 Changes in composition and structure of ileal mucus in Crohn’s disease patients compared to healthy controls

Abstract

Abstract Background Crohn’s disease (CD) is a chronic transmural disease that can affect any part of the gastrointestinal tract. Typically, the terminal ileum is impacted. The pathogenesis of this disease results from a complicated interaction of multiple factors, with the intestinal barrier playing a critical role. The intestinal barrier in the ileum is comprised of epithelial cells that are coated with a mucus layer. This barrier is permeable to nutrient absorption and microbiota. Detailed analyses of human ileal mucus are currently absent. Our study aimed to comprehend the function of mucus and the biophysical and biochemical stimuli that exist in the mucus layer during ileal inflammation, in contrast to the healthy state. Methods We enrolled 28 patients diagnosed with Crohn’s disease (CD) and 27 healthy individuals as part of our study. Mucus and biopsies from the terminal ileum were collected during a colonoscopy. The extent of clinical, endoscopic and histologic inflammation in the terminal ileum at the time of collection was evaluated using the Harvey-Bradshaw Index, Simple Endoscopic Score, and modified Naini and Cortina score. The disease trajectory and dietary behaviors of all patients and healthy controls were documented. Samples were processed following protocols for various analyses, including rheology, proteomics and scanning electron microscopy (SEM). Results Our study presents the first data on the rheology and viscoelastic properties, of human ileal mucus. Interestingly, we discovered notable variations in the viscoelastic properties of mucus in CD patients compared to healthy individuals. Furthermore, the mucus mesh size and structure differed in CD patients in comparison to healthy controls. The SEM pictures also displayed these quantitative changes. We further assessed clinical characteristics, encompassing duration of disease, and observed certain variations, although their significance is not yet statistically established. A distinct profile was detected in CD patients compared to healthy controls using proteomic analysis. The ileal mucus of CD patients demonstrated elevated levels of ITGB2 and S100 proteins, which are involved in inflammatory pathways. Moreover, a correlation was found with histologic inflammation at the time of the collection. Conclusion In our study, significant changes in mucus composition and structure were found in the terminal ileum of CD patients, compared to healthy controls. This preliminary analysis provides a basis for further investigations to establish correlations between mucus composition and viscoelastic properties, and the subsequent effects on the underlying epithelial barrier.