Altering microbiome structure and function by gut microbiota manipulation

IBD is associated with an aberrant gut microbiota, and alteration of the gut microbiota is a potential therapeutic strategy for these diseases. Key steps in the pursuit of this novel therapy for IBD are 1)identifying bacterial strains and consortia that influence IBD associated immune populations and colitis and 2) developing strategies to manipulate the gut microbiota to arrive at the most colitoprotective state for IBD. We have previously found that wild type ex-germ-free mice colonized with stool samples from individuals with IBD have increased Th17 and decreased RORgt⁺Treg cells in the colonic lamina propria, while ex-germ-free colitis-susceptible T cell transfer mice have increased colitis severity when colonized with IBD stools. More recently, we have identified individual strains and defined consortia that either expand or decrease these populations and demonstrated that stable baseline immune states formed by initial colonization with a defined gut microbiota can be stably and predictably altered to new immune states with the addition of gut microbes administered as a defined microbiota transplant. We are now developing tools to more quickly identify therapeutic and pathobiont strains, as well as efficient human engrafting strains from FMT studies, with the goal of advancing live biotherapeutic products for IBD and identifying mechanisms of microbiota induced pathogenicity and colitoprotection to explore in phase 1 clinical trials.