This research project investigates the interactions between colonizing Candida albicans cells and the GI tract environment. GI colonization with C. albicans is common for humans and generally does not have adverse effects on human health. However, if a patient becomes immunocompromised, colonizing C. albicans cells can escape the GI tract, reach the blood stream and cause disseminated disease. GI colonization is therefore significant because disease-causing fungal cells arise from the populations that colonize the host as harmless commensals. In addition, preliminary results show that, under certain conditions, colonization with C. albicans increases the resistance of the host to lethal challenge with an enteric bacterial pathogen. The long term goals of the proposed research are to understand the mechanisms by which C. albicans alters the GI tract environment and affects host resistance to challenge. The focus of Specific Aim 1 is to identify C. albicans activities that detoxify antimicrobial compounds. In Specific Aim 2, the goal is to understand how C. albicans alters the metabolite milieu of the GI tract. The studies proposed in Specific Aim 3 will analyze the effects of C. albicans colonization on the composition of the gut microbiota. These studies will increase the understanding of the interplay between C. albicans and the mammalian GI tract environment. Deeper understanding will enable development of novel interventions that harness the beneficial effects of C. albicans in the GI tract.