Dietary Amino Acids Allow Pathobionts to Thrive in Patients with Crohn’s Disease.

Adherent-invasive Escherichia coli (AIEC), a pathogenic form of E. coli, is known to accumulate in the intestinal mucosa of patients with Crohn’s disease (CD). Although it is believed that AIEC exacerbates the disease by promoting intestinal inflammation, the precise mechanism underlying the abnormal expansion of AIEC in the intestinal mucosa remains largely unknown. We have found that AIEC prefers amino acids as a source of nutrients during inflammation and this nutritional preference is critical for its ability to gain a competitive edge over commensal non-pathogenic E. coli. Importantly, we have demonstrated that intestinal amino acids used by AIEC as nutrients are mainly derived from the diet and, therefore, the removal of certain key amino acids from the diet will prevent AIEC from thriving in the gut. In this study, we will aim [1] to clarify the role of dietary amino acid utilization by AIEC in the development of intestinal inflammation and [2] to unravel the mechanisms by which intestinal inflammation regulates the substrate preference of AIEC. A successful completion of this project is expected to result in the development of novel therapeutic strategies that will control the pathogen by restricting the availability of its preferred source of nutrients.