Unveiling the Microbial Impact on Intestinal Fibrosis

To perform flow cytometry, RNAseq, metatranscriptomics, transcriptomics and lipidomics on CD and non-IBD cells

Crohn's disease (CD), belonging to the class of Inflammatory Bowel Diseases, is a chronic
 inflammatory disorder that may affect any location of the gastrointestinal tract. It is
 characterized by transmural inflammation and an overwhelming immune response of the gut
 mucosa, which leads to severe clinical symptoms. More than 50% of CD patients develop a
 penetrating or stricturing disease due to fibrostenosis, which most of the time requires
 surgical intervention since no therapies have been found as effective yet. Among the
 histological features of stricturing CD, the thickening of the muscularis mucosae and
 muscularis propria is the main hallmark, primarily due to the excessive proliferation of
 mesenchymal cells and the increased accumulation of a collagen-rich extracellular matrix in
 the submucosa, caused by multiple mechanisms, including i) the proliferation of existing
 local fibroblasts, the induction of both ii) epithelial-to-, and iii)
 endothelial-to-mesenchymal transition. Even if the alteration of these mucosal functions is
 mainly caused by the continuous tissue injury occurring during CD-associated chronic
 inflammation, recent reports suggested that CD associated fibrosis may be driven by
 inflammation-independent triggers, such as microbiota dysbiosis.
 
 Shedding the light on this aspect of CD fibrosis may lead to the development of innovative
 therapeutic strategies eventually blocking the gut thickening.