Mechanism of action of potential live biotherapeutics for the treatment of inflammatory bowel disease

Disruption of the gut microbiota shows consistent correlation with susceptibility to Crohn’s Disease and Ulcerative Colitis. Specific members of the healthy gut microbiota can influence immune homeostasis in a variety of ways. For instance, bacteria can skew the composition of the microbiota, strengthen gut barrier function, and drive maturation of intestinal T cell subsets. We investigated the immune-potentiating effects of a number of candidate commensal bacterial strains, with specific emphasis on the mode of action and protection against IBD in
mouse models of colitis. Bacterial strains were studied in vitro (intestinal cell culture systems) and in vivo (acute and chronic colitis in mice). Characterization of host bacterial interactions was performed using a multi-omics approach, including bacterial genomics, microarrays and FACS analysis. Two potential live biotherapeutic bacterial strains work in distinct ways to induce immune homeostasis. One strain directly influences the NF-úB intracellular signalling cascade to reduce the pro-inflammatory response. The other strain is able to induce the expansion of CD3+CD4+CD25+FoxP3+ regulatory T cells through secreted and cell surface-associated molecules.
Candidate bacterial strains have been identified that provide protection against murine IBD through distinctive mechanisms. Translation of their important immune-regulatory effects into human systems will now be assessed.