Project Summary Diabetes mellitus increases the prevalence and severity of periodontal diseases. Periodontitis has a complex bacterial etiology, and the relationship of the bacterial community to diabetes remains unclear. A potential mechanism for the interaction of periodontitis and diabetes is that diabetes causes a shift to a more pathogenic bacterial burden as the result of alterations in substrates such as glucose or inflammatory products that promote growth of certain bacteria. Studies have established that diabetes enhances susceptibility to infection by pathogenic bacteria in several target organs, and that diabetes causes a shift in the gut microbiota. Whether diabetes creates an environment that supports a more pathogenic bacterial community in the periodontium has not been settled in part because of technical limitations of previous studies. With advances in approaches to study the dynamics of complex bacterial communities, it is now possible to compare the microbiota in healthy individuals to diabetics. We plan to obtain microbial profiles by high throughput Illumina DNA-seq analysis before and after reversal of diabetes and to examine functional bacterial differences by RNA-Seq. A recent development has provided an opportunity to compare diabetes and normoglycemia-associated subgingival bacterial communities. Laparoscopic sleeve gastrectomy surgery produces a rapid resolution of diabetes in most recipients. The reversal of diabetes has provided new insights into the impact of diabetes on the gut microbiome. We will advantage of this opportunity to conduct two studies. One is a cross-sectional analysis to compare the microbiome in diabetics with nondiabetics. The second is a longitudinal comparison in the same subjects to examine the effect of reversing diabetes. Because the reversal of diabetes is rapid it facilitates examination of cause and effect relationships. The two approaches taken (baseline and longitudinal) each has distinct strengths so we can determine whether diabetes alters the subgingival microbiome to enhance the risk of periodontitis. This project brings together two leading bariatric surgery programs at Temple University and the University of Pennsylvania to ensure an adequate patient population to reach the planned enrollment figures. It also brings together experts in diabetes from Temple University and University of Pennsylvania, and experts in the oral cavity and oral bacteria from Penn and Ohio State University.