Developing a Model to Study Commensal Translocation during IBD

Abstract

Inflammatory bowel diseases (IBD) is severe inflammation of the gastrointestinal tract. This can lead to a breakdown of mucosal barriers, causing dissemination of commensal bacteria throughout the body. To better understand bacterial translocation during IBD, aim to develop a fluorescent microbiota in mice that we can interrogate using live imaging techniques. 
 Our preliminary experiments depleted commensals using broad-spectrum antibiotics, and replaced these microbiota with a fluorescent E. coli strain. The length of time that E.coli stays in the mice gut were monitored. We show that E. coli can persist in the ‘germ-free’ mouse gut for at least 21 days; control mice lose all added E. coli by 8-14 days. The establishment of the E. coli colony suggests this could be a reasonable model to study bacterial translocation. We are currently going to treat the colonized mice with DSS to induce colitis, and then to study translocation of E. coli by intravital microscopy. Considering E. coli is only a fraction of the normal microbiota and perhaps not a relevant model, future work aims at making a fluorescent microbiota consisting of multiple endogenous murine microbes. This will entail the use of a bacterial conjugation system capable of ubiquitously transforming many microbial species.