Characterizing the immunomodulatory effect of a microbiome-based therapy for the treatment of ulcerative colitis 3457

Abstract Description Microbiome-based therapies are being developed to treat complex diseases like ulcerative colitis (UC). The premise of these therapies is that they target both, the host and the gut microbiome. Our lab has developed BioPersistTM, a bio-engineered version of the probiotic E. coli Nissle 1917 (EcN) introduced with a persistence feature. BioPersist has shown protective effects in acute and spontaneous UC models. To further characterize how BioPersist impacts the gut microenvironment, we treated Muc2-/- mice (a spontaneous UC model) p.o. with vehicle, EcN or BioPersist. Although the gut microbiome remained unchanged, BioPersist-treated mice had reduced fecal calprotectin and mucosal infiltrating macrophages and neutrophils, key drivers of UC. Further analysis of the colon’s lamina propria cells showed that BioPersist treatment decreased % of eosinophils, macrophages and neutrophils; moreover, BioPersist-treated mice had populations of CD103+ cells and macrophages with significantly lower secretion of TNF-α, a known therapeutic target for UC, along with increased % of Foxp3+ Treg cells. Altogether, our results indicate the immunomodulatory effect of BioPersist in the gut environment that ultimately protects Muc2-/- mice from severe colitis. Future studies will focus on characterizing how the immunomodulatory effect protects against metabolic dysfunction associated with UC Funding Sources Consejo Nacional de Humanidades, Ciencias y Tecnologías (CONAHCyT), Crohn’s and Colitis Canada (CCC) and Michael Smith Health Research Innovation 2 Commercialization phase 1 and phase 2 (partnered with Melius MicroBiomics Inc.). Topic Categories Mucosal and Regional Immunology (MUC)