Identifying the driver of penetrating fibrosis in Crohn’s disease.

People with Crohn’s disease (CD) often experience intestinal fibrosis, a result of chronic inflammation that thickens the gut wall, forms scar tissues and narrows the digestive tract, leading to blockages. This persistent fibrotic process necessitates multiple surgeries over a person’s lifetime. Currently, there are no targeted medications for fibrosis due to a lack of understanding of its root causes. Hence, it is crucial to identify early fibrogenic drivers to prevent further fibrosis. Our approach involves studying the influence of gut cells, the gut microbiome and physical bowel movement on initiating the early fibrotic process. We aim to identify key drivers of early fibrosis by using a bioengineered fibrotic Crohn’s disease-on-a-chip model with patient-derived cells and simulated abnormal bowel movements. Our objectives include testing for abnormalities of gut cells and the microbes that trigger early fibrosis (AIM 1), investigating the impact of abnormal bowel movements on the early fibrotic process (AIM 2) and exploring the role of microbial components in initiating CD fibrosis (AIM 3). Our ultimate goal is to develop strategies for preventing early fibrosis in CD, significantly enhancing the lives and quality of life for CD patients with devastating fibrosis.