PROJECT SUMMARY/ABSTRACT Oral Health is fundamentally tied to general health. However, oral health and general health are perceived as separate entities. Pathologies that arise in the mouth can have a profound impact on systemic health. Periodontitis is a microbiome mediated oral inflammatory disease that affects nearly 10% of the global population and 50% of Americans aged �30 year. Periodontitis and associated bacteria have been reported to contribute to the pathogenesis of several systemic diseases, like inflammatory bowel disease (IBD), diabetes, endocarditis, rheumatoid arthritis, Alzheimer’s Disease, preterm birth, and osteoporosis. IBD is a chronic inflammatory disease of the gastrointestinal tract, and primarily includes Crohn's disease and ulcerative colitis. IBD has a high prevalence in Western societies and >3 million people are affected by it in the US. Both periodontitis and IBD impose enormous social, psychological, and economic burden on people and health services. To date, the etiology of IBD remains largely unknown, and the potential causal role of periodontitis and associated bacteria in IBD remains poorly investigated. The long-term goal of the proposed research is it to elucidate the molecular mechanisms governing periodontitis process and the potential causal role of periodontitis and associated bacteria in IBD. This project leverages complementary in vitro and in vivo mechanistic approaches and next generation sequencing to pursue the following aims- a) determine the transcriptional and epigenetic landscapes that shape oral microbiota and periodontal disease process; and b) identify oral and gut bacteria involved in eliciting IBD and the associated molecular mechanisms. Our project defines complex interrelationship between periodontitis and IBD. Results from our study will not only guide in effectively improving oral health but will also help in minimizing the risk of IBD in susceptible individuals. Thus, our study will have a far-reaching impact.