A revolution in human microbiology is in progress that will have profound health implications. The microbial cells that populate the human body (the microbiota) outnumber the cells of the body itself by an order of magnitude, and the number of genes in their collective genome (the microbiome) exceeds that of human genes by two orders of magnitude. Viewing the human and its microbial and viral components as intimately intertwined as a superorganism has broad implications;as one immunologist described this shift in thinking, "is not dissimilar philosophically from the recognition that the Earth is not the centr of the solar system." Research using mice colonized with known microbiota (gnotobiotic mice) has provided fundamental, and previously unobtainable, insights into the pathogenesis of many diseases including inflammatory bowel diseases (IBD;Crohn's disease and ulcerative colitis) and colon cancer. In addition, it is clear the intestinal microbiota affect energy metabolism, thus having a substantial potential role in nutrition, obesity, and "metabolic syndrome," and in turn development of type 2 diabetes, hypertension, and atherosclerosis. Most recently, evidence has begun to appear that microbiota also affect development of hypersensitivity diseases such as asthma. In order to support the progress of microbiome studies for 19 UAB investigators with >$12.5M in active extramural funding and about $10.9M in pending applications, we request funds to expand the capacity of the UAB Gnotobiotic Facility. The UAB Gnotobiotic Facility was established a decade ago and is now in need of additional space and equipment to accommodate the increased needs of investigators whose research is dependent on these important animal models. To meet investigators needs we propose to renovate 1,734 nsf of animal facility space currently used for storage, animal housing and procedure space to accommodate state-of-the-art, semi-rigid isolators appropriate for research using gnotobiotic rodents;purchase 40 semi-rigid isolators (6 banks) for gnotobiotic animal housing;purchase a dedicated bulk autoclave, purchase a mobile, hydraulic man lift for safe access to stacked isolators, and purchase an anaerobic chamber for the culture of bacterial inocula and experimental samples. The renovation and equipment acquisition will 1) enhance biomedical research by deriving, housing, and providing the gnotobiotic rodents for use in studies by UAB investigators whose efforts are focused on understanding microbial-host interactions;2) Maintain healthy animals by updating the existing environmental (HVAC, lighting) control and monitoring equipment;upgrading emergency power to ensure continuous isolator operation;and acquiring and installing an autoclave and semi-rigid, HEPA- filtered isolators for the biosecurity of valuable gnotobiotic mouse strains;and 3) promote healthy ergonomic practices, prevent human injuries and prevent exposure to biological hazards.