Increasing Gut Retention of Probiotics By Targeting Extracellular Matrix Proteins in IBD

Inflammatory bowel diseases (IBD) are chronic, relapsing inflammatory conditions of the intestinal mucosa within the gastrointestinal (GI) tract, mainly Crohn’s disease and ulcerative colitis. Exact pathogenesis of IBD remains unknown, but development is believed to be related to genetics, dysbiotic host-microbe interactions, immunological dysregulation, and the environment. Most IBD therapeutics are anti-inflammatory agents with alterations to the broad immune system and do not directly aim to modulate the gut microbiota. As a result, probiotics, which are viable microbes that exert positive health effects, have been used as therapeutics in GI disorders as they restore the homeostatic conditions of the gut microbiome. Yeast probiotic Saccharomyces boulardii is an example of this and is hallmarked by its physiological properties for survival to the lower GI tract that allow for its success as a probiotic. Additionally, S. boulardii possess a repertoire of genetic engineering tools allowing for various phenotypic changes that may confer new functions to the microbe. However, like many probiotics, S. boulardii has a short gut residence time due to colonization resistance from other gut resident microbes and the harsh conditions of the upper GI tract. This ultimately limits the efficacy of S. boulardii to exert its probiotic potential and could thus benefit from an increase in gut retention time. This study explores the use of a targeting moiety using genetic engineering tools to enhance gut retention of the probiotic, S. boulardii, to serve as a therapeutic in IBD treatment.