Contribution of the Gut Microbiota to Intestinal Fibrosis in Crohn's Disease.

In Crohn's disease (CD), intestinal fibrosis is a critical determinant of a patient's prognosis. Although inflammation may be a prerequisite for the initiation of intestinal fibrosis, research shows that the progression or continuation of intestinal fibrosis can occur independently of inflammation. Thus, once initiated, intestinal fibrosis may persist even if medical treatment controls inflammation. Clearly, an understanding of the pathophysiological mechanisms of intestinal fibrosis is required to diminish its occurrence. Accumulating evidence suggests that the gut microbiota contributes to the pathogenesis of intestinal fibrosis. For example, the presence of antibodies against gut microbes can predict which CD patients will have intestinal complications. In addition, microbial ligands can activate intestinal fibroblasts, thereby inducing the production of extracellular matrix. Moreover, in various animal models, bacterial infection can lead to the development of intestinal fibrosis. In this review, we summarize the current knowledge of the link between intestinal fibrosis in CD and the gut microbiota. We highlight basic science and clinical evidence that the gut microbiota can be causative for intestinal fibrosis in CD and provide valuable information about the animal models used to investigate intestinal fibrosis.