The microbiome impacts human health and influences all organ systems, extending from the skin to the gut and from bone marrow to the brain. Exciting and potentially important correlations between the microbiome and various diseases and conditions have been made, and interest in exploiting this new knowledge and mining the microbiome and its associated metabolome to develop new approaches to treat these diseases is growing in academic, biotech and pharmaceutical circles. Associations between microbiota composition and metabolic, inflammatory, autoimmune, infectious and neurologic diseases are, in some cases, sufficiently significant and impressive to warrant clinical study. The Duchossois Family Institute investigates the microbiome and its component commensal microbes with the goal of reducing susceptibility and/or enhancing resistance to a range of human diseases and inflammatory conditions. The studies supported by the DFI and its metagenomic and metabolomic core facilities will lead to and exploit new discoveries in the microbiome field to optimize host defenses against disease and reduce unwanted inflammatory conditions.